L ECTURE 3: P ASSIVE P ROPERTIES OF M EM BRANES

A long tradition in cellular neurophysiology takes the complex plasma membrane of a neuron and
reduces to it fundamentals of biophysics. By this approach the electrical properties of biological
membranes can be studied and appreciated from the point of view of electric circuits and of electric
cables. Laws of physics become the bedrock for understanding how a single neuron responds to
what other neurons tell it at thousands of synapses, how those synaptic inputs combine to move the
membrane potential toward or away from threshold for generating action potentials, how action
potentials move down an axon to its many terminals and how the depolarization of an action
potential leads to release of neurotransmitter from those terminals. Each of these is topic covered in
the present lecture.

The Nernst Equation and GHK describe the contribution of a single ion or multiple ions to the
membrane potential of a neuron, but they do so only under conditions that are not changing. These
are referred to as steady-state conditions and they exist ever so rarely in a neuron. Most neurons
of the brain and spinal cord (the CNS) receive hundreds, even thousands of synaptic inputs per
second and most generate action potentials in the range of 10/second even when they are not
optimally stimulated. The electrical properties of neurons change all the time and GHK fails to
capture those changes, either across time or across the surface of a neuron. To appreciate how
electrical current flows through the plasma membrane of a neuron or along the surface of that
membrane, how it changes over a period of milliseconds or across a distance of millimeters, we
need to look at the passive membrane properties of that neuron. These are properties that do not
change so long as a neuron’s membrane potential is below threshold for generating action
potentials. And there are three of them; they are the resistance of a membrane (rm) to the flow of
current (or its reciprocal, the conductance (g) of the membrane to the flow of current), the
resistance of the internal environment (ri) to the flow of current down an axon or a dendrite, and
the capacitance of the plasma membrane (Cm) to store electrical charge.

THE PLASMA MEMBRANE BEHAVES ELECTRICALLY LIKE AN RC CIRCUIT. Two electrical

properties dominate the behavior of the plasma membrane during rest and during movement of ions
across the membrane or along the membrane. One of those is membrane resistance (R) and the
other is membrane capacitance (C); and so the plasma membrane is often described electrically as
an RC circuit. The two are arranged in parallel (Figure 1) because current flowing across the
plasma membrane can – at least in theory – enter either the capacitor, in which case it is capacitive
current, or the resistor (conductor), in which case it is resistive current.

Fig 1. A channel composed of several subunits allows

ions to pass and thus allows current to flow. But that
current flows against a resistance – R – that has a lot to
do with the size of the pore. In addition, the exceedingly
thin membrane that separates surfaces with a potential
difference (the membrane potential) produces a
separation of charge or capacitance – C. The
membrane can be modeled as an RC circuit.

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R ESISTANCEAND CAPACITANCE ARISE FROM THE UNEVEN DISTRIBUTION OF CHARGE
ACROSS THE PLASMA MEMBRANE . Current is carried by ions as they flow through very narrow
channels in the plasma membrane (Figure 1). Because channels are narrow and because some parts
of every channel are, themselves, electrically charged, ions meet with measurable resistance as they
move from one side of the plasma membrane to the other. That is membrane resistance (Rm), and it
is a description of how difficult it is to move current through the membrane. Each channel has its
own resistance and, when we think at the level of single channels, that value is important, but the
key to membrane resistance for a segment of an axon or a length of dendrite is the number of
channels open in them at any moment. These include the number of leak channels – those that are
always open – as well as the gated channels that pop open for a few milliseconds. As the number of
open increases, Rm shrinks and as the number decreases, Rm grows. Investigators will very often
use the reciprocal of resistance to describe how easy it is to move current through a membrane.
They will speak of conductance (g) when they describe the behavior of a large patch of membrane
and of single channel conductance (γ) when they describe the behavior of one ion channel.

In parallel with Rm is membrane capacitance (Cm; Figure 1); it is the natural and unavoidable
product of separating two charged media with a non-conducting barrier. Separating
extracellular fluid from cytosol is a plasma membrane, 3-5 nanometers wide. Those two media –
extracellular fluid and cytosol – are composed principally of salt water, which is a very conductive
fluid; and the two fluids have different electrical charges, the product of which is the membrane
potential. As a result of separating fluids of different charges with an insulator – this the
phospholipid-rich plasma membrane – that is extremely thin, charge accumulates along the two
surfaces of the plasma membrane. Negative charges on the cytosolic side of the plasma membrane
separated from positive charges on the extracellular side attract each other strongly because the
barrier separating them is so thin. An analogy is the attraction between positive and negative poles
of two magnets, separated by a thin sheet of paper. The result is storage of charge; and that is
called capacitance. Three things determine the capacitance of a circuit; one of those is the nature
of the material that separates two charged sides (phospholipids of the plasma membrane), a second
is distance between the two charged sides (3-5 nm) and a third is just how much material is there is
separating the two sides (the surface area of the plasma membrane). All of these work together to
produce a significant capacitance for a neuron, or any other eukaryotic cell.

Fig 2. In a more complete equivalent

circuit, the contribution of each ion is
considered separately. Both the driving
force on each ion – here represented by
the equilibrium potential for each – and
the conductance (g) of each ion determines
its contribution to membrane potential.
Membrane capacitance is the storage of
charge due to separation of charged media
by the thin, non-conducting plasma
membrane.

AN ACCURATE EQUIVALENT CIRCUIT OF THE NEURONAL PLASMA MEMBRANE INCLUDES

SEPARATE CONDUCTANCE FOR EACH ION. To accurately portray the electrical behavior of a typical

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neuron, an equivalent must include a separate conductance for the ions, K+, Na+ and Cl-, and it must
include a separate electromotive force for each ion (Figure 2). That force is the driving force (Vm –
Ex) on each ion, which acts much as a battery does in a non-biological circuit. The circuit in
Figure 3 rightfully assumes the same Vm for all channels, and so each battery is labeled with
only the equilibrium potential for that ion. How current moves in this circuit is illustrated by the
+ and – signs; within a battery, current is said to move from + pole to – pole, but out of the battery
and through the rest of the circuit, current flows in the direction of the + sign. So if K+ channels
are open, current flows toward the extracellular side of the membrane: this ion moves from cytosol
to extracellular fluid. When Na+ channels open, current flows from the extracellular side
(extracellular fluid) to the cytoplasmic side (into cytosol). And if Cl- channels open, the inward
flow of this negatively charged ion means current flow is outward (to the extracellular side).

R ESISTIVE CURRENT AND CAPACITIVE CURRENT DIFFER FUNDAMENTALLY . Only when

current flows through a resistor will it lead to a change in voltage. That much is clear from Ohm’s
law, where voltage (V) equals the product of current and resistance (IR). Given current flow
through an RC circuit (Figure 1), only the resistive current contributes to membrane potential. But
current always flows through the path of least resistance, much like a typical college student
choosing courses for the semester. That means current will flow first into a capacitor and only
when that capacitor begins to hold as much charge as it can (that is, when the capacitor is charged)
will the current enter a resistor. And since resistors do indeed resist the flow of current they, too,
will slow its movement across the plasma membrane. The result is a delay in the time it takes for
current entering a neuron to change the membrane potential of that neuron. We will see, then, two
forces that slow the change in membrane potential when current begins to flow across the plasma
membrane. They are the capacitance of the membrane (Cm) and the resistance of the membrane
(Rm).

R ESISTIVE
CURRENT AND CAPACITIVE CURRENT CONTRIBUTE SEPARATELY TO THE
BEHAVIOR OF A NEURON . Let us think through an experimental approach to studying the
contribution of Rm and Cm to the response of a neuron when it is depolarized. To make things
simple, let us picture the response of one theoretical circuit that has only resistance, one that has
only capacitance and one that has both (Figure 3). Apply a square-wave pulse of current to a
resistor (square wave means the current comes on instantaneously, stays on for as long as you wish
to keep it on and then stops as soon as you turn it off). With a resistor only, the change is voltage is
instantaneous (Figure 3A), both when you turn on the current and when you turn it off; the resistor
simply determines how much voltage changes when a certain value of current is applied because V
= IR. Now let’s have the current flow into a capacitor only (Fig 3B) and we will find the voltage
change is not instantaneous and it continues for as long as the current is left on, with a slope that is
equal to current divided by capacitance (i/C). So, either resistor alone or capacitor alone fails to
capture what happens in a neuron because its membrane has both electrical properties. But put a
resistor and capacitor in parallel and what you see are two distinct currents (Fig 3C). Capacitive
current starts out instantly and strongly because all current flows into it at first; current continues to
flow into the capacitor until it is charged (that is, until it holds as many positive charges as it can,
given its physical makeup). As the amount of current flowing into the capacitor decreases the
amount flowing into the resistor increases and only then does the voltage change. The value for
voltage will reach a peak dictated by the amount of resistance. That means the combination of

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resistor and capacitor produces a change in membrane potential very much like that seen in a
neuron when some source of current is applied – the flow of positive charge across the plasma
membrane experiences delay, principally because of capacitance, and it reaches a limit, entirely
because of resistance. Then turn off the current and the first thing that happens is discharge of the
capacitor. Current flows out of the capacitor and into the resistor, and so even after the current has
been shut off, resistive current continues for a while longer. Movement of positive charge out of the
capacitor and into the resistor prolongs the effects of current on the membrane potential. The
change in membrane potential is not square wave but has a pronounced tail to it. The bottom line is
this: membrane capacitance acts very much like a reservoir for charge; filling it up takes time
and emptying it takes time, so that the change in voltage which occurs in response to current
happens slowly. Both the beginning of the voltage change is slowed and so is its end.

Fig 3. If the membrane were composed only of

resistance to the flow of current then the voltage
you would record with a square wave of current
injection would be, itself, a square wave (A).
But if the membrane were only a capacitor (B)
then the change in voltage over time (dV/dt)
would not be a vertical line; it would have a
slope equal to the current (i) divided by the
capacitance (C). And the total amount of
charge (Q) stored by the capacitor would be
equal to the change in membrane potential (V)
times the capacitance (C). Plasma membranes
have both resistance and capacitance, so in
section C there is a contribution from both
resistive current (iR) and capacitive current (iC).
The slow increase and decrease in voltage (V)
are the result of current flowing into and out of
the capacitor.

D shows these elements in a single diagram and

adds the contribution of internal resistance (ri)

T HE TIME C ONSTANT DESCRIBES THE DELAY IN VOLTAGE CHANGE PRODUCED BY THE

FLOW OF CURRENT . Any change in membrane potential comes on slowly and fades slowly
when current begins to move across the plasma membrane of a neuron. If we introduce a square-
wave pulse of current into a neuron and record the change in membrane potential over time we will
notice the rate of change is not linear. It is exponential (Figure 4), in that slope of the curve changes
with time. That slope can be described with the use of a time constant (τ). If we plot the change in
membrane potential over time, we find the change at any one time (what we will call ΔVm) is
proportional to the size of the final change in membrane potential (V!). The two are related by the
factor 1- e-t/ , where t = the time at which we are measuring the membrane potential, and τ is the
τ

time constant for that chunk of membrane.

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 Fig 4. A square-wave pulse of current produces
a change in membrane potential (ΔVm) that
reaches maximum (V!) and returns to resting
levels much more slowly than the current. Both
the rate of rise when current is turned on and
the rate of decline when current is turned off are
exponential. The slope of the curve at any time
during its rise can be described mathematically
by an equation that takes the final value for
change in membrane potential (ΔV!) and
multiplies by the term 1- e-t/ . Pick any one time
τ

that we can call t, and we will find the slope of the curve at that time is determined by a membrane
constant, referred to as the time constant, designated by τ. The quotient, t/τ, is an exponent, so that
e raised to the negative value of t/τ is the variable that changes as time changes. 1 minus the value
of e raised to the negative value of t/τ then tells us exactly how much the voltage has changed in the
moments after current begins to flow.

THE TIME CONSTANT IS A MEASURE OF TIME. Although this may sound painfully obvious to you,
the time constant is a period of time that can be measured in milliseconds. τ is time; it tells us how
much time must pass before the membrane potential of a neuron changes from one value to another.
Let say you want to know the change in membrane potential (ΔVm) produced by the flow of current
at some period after the current begins (we will call that time t). And let’s deal with the situation
where you know what is the final value for the change in membrane potential (this we will call
ΔV!). That value at any time t is not linear – it is exponential – which means if it takes 6
milliseconds for a membrane to reach its final value (again, we will call this ΔV!) it does not reach
1/6th of the final value during each of those milliseconds. The membrane potential changes a great
deal during the first millisecond but not so much during the second and not nearly so much in the
third (Figure 4). That feature is true for the entire length of any neuron, but the time it takes for a
neuron to reach ΔV! varies from one part of a neuron to another, because each piece of a neuron’s
membrane has its own time constant, τ.

We can define τ for a specific piece of a neuron’s membrane as the time it takes for the change in
membrane potential (ΔVm) to reach 63% of its final value (ΔV!). The value of 63% is not invented
out of whole cloth, but falls out from the equation that describes the slope of the curve when ΔVm is
plotted against time (Figure 4). To see how it works, let us inject current into a neuron and measure
the change in membrane potential (ΔVm) at particular time, t. And let’s make the time at which we
measure the change in membrane potential equal to the time constant (τ) of that piece of a neuron’s
plasma membrane. We can use a simple equation to relate ΔVm (the change in membrane potential
at any time we choose to measure it) to the final change in membrane potential (V!):

ΔVM = ΔV! (1- e-t/τ )

If we choose a time t that is equal to the time constant (τ) we find the equation becomes:

ΔVm = ΔV! (1- e-1)

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e-1 = 0.37 and since 1-0.37 = 0.63, that makes ΔVm = 0.63ΔV! at a time, t, equal in length to 1 time
constant (τ).

To make this a bit more intuitive, we can make the following absolute statement:

At a time equal to 1 τ following the introduction of current to any piece of membrane, the
change in membrane potential (Δ Vm) is 63% of what that change will be when all is said and
done (Δ V!).

What if we choose a time to measure the change in membrane potential that is twice as long as the
time constant? In that case ΔVm = V! (1-e-2); because e-2 is 0.14 we can say after a period of time
equal to 2 τ, the change in membrane potential is (1 - 0.14) or 86% of its final value (Δ V!).

Picture the following experiment. Let us inject enough current to produce a final change in
membrane potential from -70 mV to -65 mV. That means the absolute change in membrane
potential (ΔV!) = 5 mV.

If you wait a period of time to equal one τ, ΔVm at that time will be 63% of 5 mV; that is a 3.15 mV,
and so the membrane potential at that time will have gone from -70 mV to -66.85 mV.

If you wait another time period equal to another τ, ΔVm will be 1-e-2 of V! And as we have just
seen, 1-e-2 = 0.86 and so the change is membrane potential will be 86% of V! or 4.3 mV. The
membrane potential will have gone from -70 mV to -65.7 mV.

And if you measure the membrane potential at a period equal to 3τ the change in potential due to
current injection will be 1-e-3 of its final value of 5 mV. Since e-3 equals 0.05, the change in
membrane potential (ΔVm) = 0.95 ΔV! The membrane potential will have changed by 4.75 mV and
so it will have gone from -70 mV to -65.25 mV. This gives you another handy number to use –
after the passage of time equal to 3τ, the change in membrane potential will be 95% of its
final value. At 4τ the change in membrane potential is 99% of its final value.

THE DECAY PHASE OF A DEPOLARIZATION OCCURS WITH THE SAME TIME CONSTANT. When
depolarizing current is turned off, the membrane potential returns to resting levels, but that decay to
resting levels is not immediate. The decay is also exponential and the exponent is, again e-t/ , but the
τ

slope of the decay is negative rather than positive. So if we plot the slope of the decay phase
relative to the absolute value of the depolarization (V!) we find the two are related by the following
-t/
equation: ΔVm = V! (e ) τ

Take the situation in which we have injected enough current to depolarize a neuron from -70 mV to
-65 mV. That makes ΔV! = 5 mV. Now turn off the current and measure the membrane potential
after a period of time equal 1τ. The change in membrane potential (ΔVm) will be e-1 ΔV! and as we
have seen e-1 = 0.37. So, the change in membrane potential is 37% of 5 mV, which is equal to 1.85
mV. The membrane potential will still be 1.85 mV depolarized relative to the resting level of -70
mV; the membrane potential will be -68.15 mV.

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T HE TIME CONSTANT FOR A PIECE OF MEMBRANE IS EQUAL TO THE PRODUCT OF Rm
AND C m . We can use the measure of membrane potential over a period of time following injection
of current to calculate τ, but we would not know which properties of a neuron account for τ. That
requires a bit more inquiry. Two things slow down the change in membrane potential as current
begins to flow into a neuron and they, therefore, are the properties we need to consider in sorting
out the time constant. One of those properties is the resistance to the movement of ions through
channels in the plasma membrane (Rm) and the other is the capacitance of the membrane (Cm). As
Rm increases so does the delay in moving current across the membrane to depolarize it; τ increases.
But as Rm shrinks, which happens when ion channels open in the plasma membrane, τ decreases.
The same is true for Cm; as it changes so does τ. An increase in Cm and in τ occurs as a neuron adds
membrane to its surface whereas a reduction in Cm and in τ usually occurs as a result of separating
the charges in cytosol from the charges in extracellular fluid – think of this as separating the
negative charges on the inner surface of the plasma membrane from the positive charges on the
outer surface of the plasma membrane. A reduction in Cm happens most commonly with the
addition of myelin to an axon. Here, then, is the equation that describes the forces that produce the
time constant for any piece of neuronal membrane: τ = CmRm. The time constant is the product of
membrane resistance and membrane capacitance.

We can use the equation, τ = CmRm to make an additional, important and obvious point. Since the
time constant is the product of these two electrical properties of the membrane, if one shrinks to
nearly zero, it does not matter if the other remains significantly high: τ will shrink to a very small
value. This simple feature of τ is valuable to a neuron: even when its Cm is substantial, an axon or a
dendrite can reduce its τ to some tiny value by opening a large number of ion channels and reducing
Rm to almost zero. Or a piece of axon can have a measurable membrane resistance but if its
capacitance is almost zero, its time constant will be tiny.

THE EFFECT OF τ IS MOST READILY APPARENT IN TWO PARTS OF A TYPICAL NEURON’S LIFE.
Action potentials move down axons at a variety of conduction velocities; the fastest conduction
velocities are more than 100 m/second whereas the slowest are 0.1 m/second. The major
determinant of that speed is τ; we will look at its role a bit later in this lecture, but for now you
should appreciate where τ is long, conduction velocity is slow and where a neuron finds a way to
make τ small, conduction velocity is fast. The other place that τ is a most important factor is along
the postsynaptic surface of a neuron (Figure 5). There, a long τ can be beneficial because it allows
the effects of depolarizing currents to add together and more easily drive the membrane potential to
threshold for generating action potentials.
Fig 5. Take a situation in which one
neuron is presynaptic to another neuron.
Record from them both as the
presynaptic neuron fires a train of
closely spaced action potentials, around
3-4 msec apart. If the postsynaptic
neuron has a τ = 1 msec its Vm will rise
and return to baseline in 4 msec (A).
That is not the case for a neuron with τ
= 10 msec. Vm will still be at or near its
peak from the release of neurotransmitter after the first action potential when the effects of a second

7
action potential reach the postsynaptic neuron. Each excitatory postsynaptic potential (EPSP) will
build upon the previous one until Vm reaches threshold for initiation of an action potential. These
observations make clear a benefit to a long τ for a dendrite or a dendritic spine of a neuron; an
increase in its value through an increase in Cm or Rm can lead a neuron to respond more easily (but
much more slowly) to a synaptic input.

The process illustrated in Figure 5 is called temporal summation. EPSPs add up over time, as a
second depolarization begins before a previous one has completely faded away (that is, before the
membrane potential has returned to resting level). As a result, two EPSPs generated at separate
times add together to bring the membrane potential closer to threshold. The length of that
summation time varies from one neuron to another, and from one place along a neuron to another,
all because τ varies. But where τ is longer summation will occur more readily.

S UMMARY : The time constant is a value of time; it describes delay in time between the
introduction of current into a cell (or its withdrawal from a cell) and the change in membrane
potential produced by that current. Add current to a cell and the membrane depolarizes – its
membrane potential changes – but it takes time to get the depolarization to its peak value. The time
constant describes how long it takes to get the change in membrane potential to 63% of its final
value. Removal of the current – turn off the switch to the power source – has the membrane
potential at that piece of membrane return to resting level, but the return is also delayed. And again,
the delay is described by the time constant for that piece of membrane. Each period of time equal to
1 τ has the change in membrane potential move by a value of 63%, whereas a change in membrane
potential after a period of time equal to 2τ is 86% of the way toward its final value. Although
described as a constant, τ is constant only for a specific part of a particular neuron. A segment of
dendrite on any neuron has its own τ but a different segment of that same dendrite or a segment of
the axon given off by that same neuron can have a very different τ. All of that is true because τ is
the product of two electrical properties that vary along the length of a neuron. The two electrical
properties that determine τ for a specific piece of membrane is the resistance of the membrane (Rm)
and its capacitance (Cm).

THE LENGTH CONSTANT (λ) IS A SECOND, PASSIVE PROPERTY OF CELL MEMBRANES. Let us take a
situation in which a depolarizing current is injected into a dendrite or an axon; that current injection
can be artificial – through a microelectrode inserted into the dendrite or axon – or it can natural,
through the opening of ligand-gated ion channels at a synapse. A microelectrode records the level
of depolarization, first at the site of current injection and then, at each of several locations at various
distances away from the injection site. The size of the depolarization will be greatest at the site of
current injection – we can call this 100% of the depolarization – and it will be progressively smaller
at progressively greater distances from the injection site (Figure 6). At some point, far away from
the injection site, the depolarization will be gone; the membrane potential will not move from its
previous, resting level. These observations tell us current leaks out of the cell along the length of an
axon or a dendrite, so that the membrane 1 mm away from a source of current is less depolarized
than the membrane at the origin of the current. And 2 mm is less depolarized than 1, 3 less
depolarized than 2, until finally all the current has leaked out of the cell and none remains to
depolarize the membrane. These things will vary – how far you need to go before all the current is
gone – because the amount of leakage differs from one place to another along a neuron, but we are

8
within the right order of magnitude if we say most current in most dendrites and axons of most
neurons moves no farther than 5 mm before it has all drained out.

Fig 6. Use two electrodes, one to inject

current into a dendrite and the other to
record in the change in membrane
potential produced by the current
injection. At the injection site the
depolarization produced by current
injection is 100%. But as you move the
electrode down the dendrite, at
increasingly greater distances from the
current injection site, the amplitude of the
depolarization shrinks to progressively
smaller values. At some point along the
dendrite the depolarization will be 37% of
its value at the injection site. The distance
between that, specific recording site and
the injection site is one space (length)
constant (λ).

T HE DECAY IN DEPOLARIZING
CURRENT ALONG A DENDRITE OR AN AXON IS EXPONENTIAL . So long as a depolarizing
current is sub-threshold – that means, so long as the depolarization does not reach threshold for
generating action potentials – the spread of current along a dendrite or an axon is passive. This
passive movement of sub-threshold current along the length of a neuron is called electrotonic
conduction. But the current decays over distance and so the level of depolarization decays over
distance. Rather than being a linear decay, in which every unit length of the membrane would lose
a set amount of current, the decay is exponential (Figure 6). The slope of the line that plots change
in membrane potential over distance is equal to the following equation:

Vx = V0 (e-x/ )
λ

Vx is the depolarization at a specific distance, x, away from the injection site, and V0 is the level of
depolarization at the injection site. The two values are related by the factor, e-x/ . Both x and λ are
λ

lengths; λ is the space (length) constant, which we can define as the distance over which 63% of the
current dissipates (37% remains), and x is some distance at which we have chosen to measure the
change in membrane potential. The of 37% of current that remains at a distance equal to 1 λ is
simple to grasp for the same reasons that the 63% value of a time period equal to 1 τ is easy to see,
because both have everything to do with e-1.

The level of depolarization at a distance from current injection site equal to 1 λ takes the equation
above and turns it into something more manageable. Let’s do that, then, and sample the level of
depolarization at a distance equal to 1 λ, that is when λ = l, which means x/λ = 1. That makes e-x/ =λ

e-1. In that case, how much of the initial depolarization – the level we saw at the site of current
entry – do we now see at that distance of x when it is equal to 1λ?

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We can calculate what it will be.

V x = V 0 (e -1 )

Because e-1 = 0.37, we can state boldly, with full confidence, that at a distance equal to 1 λ, the
amplitude of the depolarization is 37% of what it is at the site that current enters the cell to
depolarize it.

At a distance equal to 1 λ, Vx = .37 V0. At a distance equal to 2 λ, Vx = .14 V0 and at a distance of

3 λ, Vx = .05 V0, and if we move the recording electrode to a distance equal to 4 λ away from the
site of current entry, 99% so much current has drained out of the cell that the change in membrane
potential is only 1% of the value we saw at the site of current entry. And so we can say the current
entering at some spot along an axon or along a dendrite has no effect on membrane potential of a
second spot a distance equal to 4 λ away.

λ IS NOT FIXED WITHIN A NEURON OR ACROSS NEURONS. The space constant, λ, varies
dramatically across locations on the same neuron and even more dramatically from one neuron to
the next. This difference in λ among neurons or along dendrites tells us how far current can flow
before so much has drained out of the cell that its effect on membrane potential becomes negligible.
If a dendrite or an axon has a large λ, the depolarization at the site of current entry can travel a long
distance before it is reduced by 63% or 86% or 95%, whereas in a dendrite or an axon with a small
λ, the depolarization dies out after much shorter distances (Figure 7).

Fig 7. Three axons or dendrites, each with a

diameter of 4 µm, have very different space
constants (λ). The one labeled a has a λ of
500 µm and so at that distance 37% (1/e) of
the current that enters at point 0 remains. The
one labeled b has a λ of 1000 µm (1 mm) and
so that is how far current must flow before it
decays to 37% of its original value. And for c,
with a λ of 2 mm, a great deal of current
remains at 500 µm and at 1000 µm. Only
when the current has had to travel down a
length of 2 mm has it and its effect on
membrane potential decayed to 37% of its
original value.

THE LENGTH OF λ DETERMINES THE EFFECT

OF SYNAPSES ON THE MEMBRANE POTENTIAL
OF THE AXON’S INITIAL SEGMENT. A typical
neuron forms synaptic contacts with many
target cells; in many cases two neurons, with
cell bodies in the same location and with
dendrites that overlap extensively, receive a common input from another neuron (Figure 8). An

10
action potential generated by one neuron can, therefore, lead to postsynaptic currents in two,
neighboring neurons. But if the two dendrites with which that one axon forms separate synapses
have different space constants, the effect of the synapses on the two neurons differs dramatically. If
it possesses a long λ of 1 mm, a dendrite allows most of the current entering at the synapse to reach
the axon’s initial segment. The synapse on that neuron is likely to depolarize the membrane of the
initial segment to threshold for generating action potentials. It will spike. But if the dendrite of the
second neuron has a much shorter λ (0.1mm), much of the current that enters at the synapse drains
out of the dendrite and very little reaches the neuron’s initial segment. The effect on the membrane
potential at the initial segment is much weaker, which means the synapse is unlikely to drive the
membrane potential at the initial segment to threshold. That second neuron fails to spike.

Fig 8. An action potential in one neuron

(a) produces EPSPs of equal size in
neurons b and c. At an initial segment 0.1
mm away from the synapse, neuron b
shows a large depolarization because λ is
1 mm. Most of the current that entered at
the synapse reached the initial segment
Neuron c, by contrast, has a λ equal to the
distance from the synapse to the axon
hillock (0.1 mm). The change in Vm is e-1
or 0.37 what it was at the synapse.

Let us plug in some values for the change in voltage illustrated in Figure 8. We can say the
synapses formed by neuron a onto both neurons b and c are particularly strong – the synaptic
conductance is high – and so neurotransmitter released from the axon terminal of neuron a produces
a 5 mV change in membrane potential at the synapse with neuron b and with neuron c. The
membrane potential in both postsynaptic dendrites goes from -70 mV to -65 mV. Now let’s
measure the depolarization at the two initial segments, each of which is 300 µm (0.3 mm) away
from the synapse.

If we measure the membrane potential at the initial segment (Vx) of neuron b we see it is
depolarized from a value of -70 mV to one of -65.5. It is depolarized by 4.5 mV, which is 90% of
the 5 mV depolarization produced at the synapse (V0). And since we know that at a distance equal
to 1λ, Vx = .37 V0 we can see the distance between the synapse and the initial segment is much less
than 1 λ.

But when we measure the membrane potential at the initial segment of neuron c we it is depolarized
by a much smaller amount. The membrane potential goes from -70 mV to -69.75 mV at the initial
segment. Again the depolarization at the synapse on cell c (V0) is 5 mV, but the depolarization at
the initial segment of cell c (Vx) is 0.25 mV. That value of 0.25 mV is 5% of the original
depolarization at V0. So Vx = 0.05 V0. Because the value of 0.05 = e-3, we know the distance
between the synapse and the initial segment is three times the length constant (the value of 5% of
the depolarization remaining at Vx is true only at a distance equal to 3 λ).

11
Why this happens – that is, why one neuron has a length constant greater than that of another
neuron – falls upon the internal resistance and membrane resistance of the two neurons. Let us see
how and why that is true.

MEMBRANE RESISTANCE AND INTERNAL (AXIAL) RESISTANCE DETERMINE THE VALUE OF λ .

There are two paths current can take once it has entered an axon or a
dendrite; it can stay inside and move down the axon or dendrite or it
can exit through the plasma membrane. Current will always take the
path of least resistance, so the question of which path current will
take – down the axon or through the membrane – boils down to a
matter of resistance. If the internal resistance is low, current will have a greater tendency to
stay inside and move down the axon. The same is true if membrane resistance is high; current
will move along the path of less resistance and will move down the axon rather than out of the axon.
That is what happens when the only channels open are leak channels and the density of those
channels is low; membrane resistance is so high, current will stay inside an axon. A different
arrangement, one of high internal resistance or low membrane resistance, drives current to move
through the plasma membrane and into extracellular space rather than move down an axon. Clearly,
then, the resistance to movement of current down an axon or a dendrite (internal resistance) and the
resistance to movement through the plasma membrane (membrane resistance) determine the length
constant. λ is proportional to the square root of membrane resistance (rm) divided by internal
resistance (ri). You might think it odd to divide resistance (rm) by resistance (ri) and wind up with
a value of length in centimeters. But ri is measured as ohms/cm whereas rm is ohms x cm; for ri/rm,
then, ohms cancel out and you get the square root of cm x cm, which equals (ta dah) cm, a measure
of length.

T HE KEY DETERMINANT O F INTERNAL RESISTANCE IS DIAMETER . Electrical current flows

well through salt water, and in the end that is what makes up most of cytosol and most of
extracellular fluid. The more salt water available to current, the more easily will that current flow.
Take a narrow glass tube and fill with 0.9% salt water and electrical current will flow through it but
if you fill a much wider tube with the same solution, electrical current will flow much more easily.
All of that goes to say diameter is the key to internal resistance (Figure 9). A wider diameter,
which means a greater volume of salt water, makes for a lower
resistance to the flow of current.

Fig 9. Axons or dendrites of different diameters have length

constants of different values. A narrow dendrite, only 1 µm in
diameter, has a short λ because its internal resistance (ri) is so
high. Current is driven out of the axon, through the plasma
membrane, and into extracellular space. An increase in radius
by a factor of 4 doubles the value of λ, and an increase in
radius by a factor 16 leads to an increase in λ by a factor of 4.
That means λ changes as the square root of radius, which
makes an increase in size a less than optimal means to increase
λ.

12
T HEDENSITY OF OPEN C HANNELS DETERMINES M EMBRANE RESISTANCE OF ALL
DENDRITES AND OF MOST AXONS . Neuronal currents are carried by ions. And ions make it
through the hydrophobic plasma membrane only when they move through channels (we can
discount the effect of pumps and exchangers because they are rare compared to channels, they work
slowly compared to channels, and they move ions much less efficiently). Were the plasma
membrane only a phospholipid bilayer the resistance of that membrane to the flow of current would
be infinitely high, but the presence of leak channels and of gated channels in the membrane reduces
the value of its resistance. The amplitude of membrane resistance (rm) depends, then, on the density
of open ion channels. For more than a generation, neuroscientists thought membrane resistance in a
typical neuron was not very high and so values of λ for dendrites were thought to be less than 1 mm.
Most of that turned out to be an artifact of the methods used in intracellular recording (the plasma
membrane was punctured and did not seal completely, which left a sizable hole through which
current flowed). Modern approaches to recording intracellular currents give a much different view;
the λ of a typical dendrite is much longer than 1 mm. Neurons are said to be electronically
compact, which means synaptic currents at the tips of very long dendrites still exert considerable
influence on the membrane potential at the axon’s initial segment. All of this is due to the high
membrane resistance of a typical dendrite in a neuron at rest.

AN INCREASE IN DIAMETER AFFECTS BOTH MEMBRANE RESISTANCE AND INTERNAL RESISTANCE,

BUT THE EFFECT ON INTERNAL RESISTANCE IS MUCH GREATER. With an increase in the diameter
of an axon or a dendrite, membrane resistance shrinks by a factor equal to the change in
circumference of that axon or dendrite.

rm = Rm/(2π a), where Rm is specific membrane resistance (the resistance per unit area of
membrane) and a is the radius.

That reduction in membrane resistance would be counterproductive to an increase in λ, were it not

for the much larger reduction in internal resistance that comes with an increase in axon or dendrite
diameter. Internal resistance is proportional not the circumference of an axon or dendrite (2π a) but
to the cross-sectional area of that axon or dendrite (π a2).

ri = Ri/π a2 where Ri is specific internal resistance (resistance of unit length).

Thus, an increase in the diameter of an axon or a dendrite produces a much greater reduction
in internal resistance than in membrane resistance. A full mathematical description of the
relationship between the two resistances, the radius of a dendrite or an axon and λ is the following:

λ = (Rm/Ri)1/2 (a/2) 1/2

The major point to carry away is this: λ is proportional to the square root of the radius of an
axon or a dendrite. That means a four-fold increase in radius produces a two-fold increase in λ,
but to get a four-fold increase in λ the radius of a process must grow by a factor of 16. Most
invertebrates take such a path toward making axons with long λ by giving off axons that are as wide
as 1 mm in diameter. Most vertebrate axons take a different approach and raise λ not by reducing ri
but by greatly increasing rm. They put myelin around axons to raise membrane resistance. That

13
feature of axons leads us to the last part of this lecture and the role played by passive properties in
the propagation of action potentials.

Summary: The length constant (λ) is a measure of distance. It describes how far along the
plasma membrane of a neuron current can flow passively (that is, without producing further opening
of ion channels) before 63% of it has drained out through open ion channels. This length constant is
proportional to the square root of the membrane resistance (rm) divided by internal resistance (ri).
Anything that keeps current in a neuron rather than allow it drain out of a neuron, produces a longer
λ. And so shutting ion channels – thereby raising rm – lengthens λ. Similarly, a reduction in
internal resistance keeps current inside a neuron. The one thing a dendrite or an axon can do to
lower ri is grow; a wider axon has a lower ri and, therefore, a longer λ. With a little help from
supporting cells – oligodendrocytes in the central nervous system and Schwann cells in the
peripheral nervous system – an axon can also attract the formation of myelin, which serves to
greatly increase rm.

P ASSIVE P ROPERTIES AND A CTION P OTENTIALS

T HE KEY FEATURE OF AN ACTION POTENTIAL IS THAT IT REGENERATES . An action

potential that begins at the initial segment propagates down the axon to all its terminals, some of
which may be more than a meter way from the initial segment. All along its length, from initial
segment to axon terminals, the action potential is the same height. It gets no smaller as it moves
down an axon (Figure 10) because all along its length, each patch of axon opens its own voltage-
gated ion channels to regenerate the action potential. Each piece of membrane makes its own action
potential as the current that enters at a previous spot along an axon drives the production of an
action potential at the next spot along the axon. All of this gets to the reason from action potentials
– they exist because signals in most axons travel for distances much greater than 1 λ. Take an
axon that carries information about temperature from the tip of your toe to your spinal cord. That is
a distance of a meter in some of us. And the axon is tiny, about 1 µm in diameter so its λ is in the
range of 0.2 mm. With a total of 5 λ per mm and 1000 mm per meter, the axon is 5000 λ long. No
amount of current injected into the axon’s start point would make it to its end point if passive
conduction was all the axon could do. And so the axon turns to action potentials.

Fig 10. A squid giant axon is electrically stimulated at one

end to generate an action potential. The action potential is
recorded at two locations (E1 and E2) that are separated
by a distance of fifteen millimeters. At both locations the
action potential leads to a reversal in membrane potential,
from a resting value close to -65 mV to a momentary peak
at +50 mV. The height does not change along the axon.
Even though location E2 is 15 mm away from E1 the action
potential at E2 is as big as that at E1. Because the distance
between the two recording electrodes corresponds to 1 λ in
a squid giant axon, a passive flow of current would decay to
37% of the value at E1. These data tell us movement of an

14
action potential is active; the current regenerates all along the axon.

A CTION POTENTIALS BEGIN AS POSITIVE FEEDBACK LOOPS . An action potential begins at

the initial segment because it is the spot of lowest threshold; it is packed with the highest density of
voltage-gated Na+ channels and they are particularly sensitive, which means they open with
minimal depolarization. When a few of these channels open in response to a depolarizing current
that moves the membrane potential from -70 mV to -55 mV (threshold) they allow Na+ to enter the
cytosol and to further depolarize the membrane which causes more channels to open which further
depolarizes the membrane, on and on until all voltage-gated Na+ channels that are able to open have
opened. This is the very definition of a positive feedback loop – one of the very few such loops in
all of nature; Figure 11 – and it explains why the action potential always rises to a value very close
to ENa.

Fig 11. The constant height of the action potential is a function of the
positive feedback loop carried by Na+. When depolarization from
synaptic input reaches a threshold value, the opening of some voltage-
gated Na+ channels leads to the opening of others and the
depolarization they carry leads to the opening of still others. On a
slower timescale voltage-gated K+ channels open and produce a
negative feedback loop that brings the membrane potential back to
resting levels within 1 millisecond.

In places other than the initial segment, the threshold for an action
potential is higher because the density of voltage-gated Na+ channels is
much lower. But those channels exist everywhere on a neuron and
when prodded into opening, they produce an action potential that is the
same height all along the surface of a neuron. What makes voltage-
gated channels open at any spot along an axon is the
depolarization of the action potential at an adjacent patch of
membrane. Whether on a squid giant axon or an unmyelinated mammalian axon each patch of
membrane regenerates the action potential because its voltage-gated Na+ channels open in response
to the depolarizing current that entered with an action potential in the preceding patch of membrane.

MYELIN AND CONDUCTION VELOCITY

MYELIN INSULATES AN AXON. Myelin consists of repeated wrapping of plasma membrane around
an axon. That wrapping is of either an oligodendrocyte arm around a segment of an axon in the
CNS or of an entire Schwann cell around a segment of an axon in the PNS. The myelin segments
cover a length of axon that is on the order of 1 mm, then there is an interruption in myelin before
the next oligodendrocyte or the next Schwann cell picks up myelinating the next segment of axon.
Those interruptions in myelin are called nodes of Ranvier and they are typically 10-50 µm long
(Figure 12). Myelin segments are unusual in many ways but of particular relevance to the
conduction of action potentials is the absence of voltage-gated Na+ channels along their lengths. So
not only is the plasma membrane of a myelin segment covered by an insulating material, but also
the means by which large amounts of current flow into an axon are missing from the segment.

15
Voltage-gated Na+ channels are, instead, densely packed in the plasma membrane of the nodes
of Ranvier. They resemble the membrane of an initial segment. And much like the initial segment
of an axon, the nodes of Ranvier are spots at which the threshold for generating action potentials is
very low. This combination of features along a myelinated axon – no voltage-gated Na+ channels in
the myelin segments and densely clusters of those channels at the nodes – makes for an interesting
phenomenon, as action potentials appear to jump from node to node. The depolarizing current that
enters at one node flows passively down the myelin segment to depolarize the next node sufficiently
to drive its membrane potential to reach threshold. Voltage-gated Na+ channels open in these next
node and the process repeats itself down the axon. This type of action potential conduction in a
myelinated axon is called saltatory conduction (from the Latin, saltare, meaning “to jump”).

Fig 12. Myelin wraps segments of an

axon, typically 1 mm in length. Between
each myelin segment is a short gap in
myelination called a node of Ranvier –
they are 10-50 µm in length. At each
node is a high density of voltage-gated
Na+ channels, whereas along each
myelin segment there are no such
channels. Current that enters at one
node moves passively along a myelin
segment to reach the next node and bring
it to threshold. As a result, the action
potential jumps from node to node in
what we refer to as saltatory conduction.

MYELIN AFFECTS BOTH MEMBRANE RESISTANCE AND MEMBRANE CAPACITANCE. The

contribution of myelin to conduction velocity is found in its effects on membrane resistance and
membrane capacitance. Myelin greatly increases membrane resistance (Rm). Layer upon layer
of phospholipids laid upon an axon is much like coating a copper wire with a thick band of
insulating material. Current leaks out with great difficulty because resistance to its flow is very
high. And where the myelin sheath is particularly thick – as it is on axons with large diameters –
the membrane resistance is particularly high. Myelin also greatly reduces membrane
capacitance (Cm). In electric terms, the insulator that separates two conducting media has a total
capacitance but where the insulator is composed of many layers, each layer carries a fraction of that
capacitance. So if a myelin sheath of a particular axon is composed of 20 wrappings of
oligodendrocyte membrane, each wrapping has 1/20th the total capacitance. That means the
capacitance of the plasma membrane would be equal to only one of those wrappings – it would be
1/20th of the value of an unmyelinated axon. An analogy can be drawn between capacitance and
magnetism. Separate two magnets by a thin sheet of paper and the positive and negative poles of
the two will attract one another very strongly. But place one magnet on top a phone book and
another on its bottom and the two magnets are barely attracted to one another. The same is true for
capacitance; when charges are separated by the thin plasma membrane (when plate separation is
tiny), capacitance is high but when many layers of myelin separate cytoplasm from extracellular
fluid, capacitance is low.

16
THE INCREASE IN RM LENGTHENS λ . Myelin’s effect on Rm drives an increase in λ – a
depolarizing current can go much farther before it is reduced by 63% or 86% or 95% - and that can
play some role in the speed with which action potentials make it down an axon, but the effects of
myelin vary across axons because the extent of myelin varies across axons. Myelin is extremely
thick around a large-diameter axon (10 µm in diameter) but is progressively thinner as the axon
diameter declines to 1 µm. This interaction between axon size and degree of myelination is the
product of chemical signaling between an axon and an oligodendrocyte or a Schwann cell; larger
axons have a greater abundance of a ligand that binds to receptors on the surface of myelinating
cells and instructs them to wrap repeatedly. The interaction between axon size and myelination
means a large-diameter axon with low internal resistance also has high membrane resistance; this
combination produces a very large λ. Conversely a smaller-diameter axon with greater internal
resistance has less myelin and lower membrane resistance – the result is a much smaller λ. In
practical terms, the effect of myelination on an axon’s λ contributes to the conduction velocity of its
action potentials by allowing an axon to spread out its nodes of Ranvier. With less membrane
devoted to regenerating action potentials and more it dedicated to the rapid, passive movement of
current, an axon will see its conduction velocity increase. Yet the major effect myelin has
conduction velocity is not in its membrane resistance or in its space constant. It is, instead, an effect
on membrane capacitance and on the time constant.

THE CHANGE IN CM PRODUCED BY MYELIN HAS THE EFFECT OF LOWERING τ. The major
contribution of myelin to conduction velocity comes with its effect on Cm and its reduction in the
time constant. That effect on τ requires some explanation. The delay in a voltage change produced
by current that flows through channels in the plasma membrane is the time constant, τ, which is the
product of Rm and Cm. And while it is true myelination reduces Cm it also increases Rm; the two
would appear to cancel out and so myelination would seem to have little effect on τ. Yet τ has two
components; the τ described so far is a constant at the site current enters the axon from extracellular
fluid, such as at a node of Ranvier. At a node, R is very low when the voltage gated Na+ channels
open and even though Cm is high at the nodes, the product, Rm x Cm is tiny and so τ is tiny. Fine,
but what happens along a myelinated segment, in which Rm reaches extreme values? The answer is
simple: Rm does not matter when we move from considering the flow of current INTO the cell and
turn our attention to the flow of current INSIDE the cell. Once current enters an axon, the
critical resistance to its flow is no longer membrane resistance but internal resistance. Thus,
there is a second τ, referred to as conduction τ or τ2, which describes the delay in current moving
down an axon or a dendrite once it has already gotten inside. Conduction τ = Cm x ri. The effect of
conduction τ on conduction velocity is apparent in the squid giant axon – because of its very large
diameter, its internal resistance is very low and so conduction τ (τ2) is tiny. The result is a
conduction velocity that exceeds 100 meters/second. Vertebrate axons reduce τ2 not by reducing
internal resistance but by reducing Cm. Myelination’s effect on Cm – its reduction of Cm by a factor
of at least 4 and as much as 50 – works to propel an action potential down an axon at speeds that
range from 10 meters/second to 120 meters/second.

Summary. Passive properties of a neuron determine the length and speed over which current
moves. For currents that produce subthreshold changes in membrane potential (these are usually
synaptic potentials), membrane resistance and internal resistance determine how far the current can
flow before it becomes negligible. Membrane capacitance and internal resistance also work to slow

17
down the current’s ability to change a neuron’s membrane potential. The effects of these electrical
properties are seen in the space (length) constant and the time constant. And the same electrical
properties are instrumental in conduction of action potentials. Whether by increasing the diameter
of their axons – thereby reducing internal resistance – or by inviting cells to wrap their axons in
myelin – thereby reducing membrane capacitance – many neurons go to great lengths to shorten
conduction τ. By doing so they greatly increase the velocity at which they conduct action
potentials. That brings us, then, to a point where we can have a fuller discussion of what goes on to
initiate and propagate an action potential; they are the subjects for the next lecture.

STUDY QUESTIONS

1) You record from an axon while injecting current through a microelectrode and you
measure how long it takes for the membrane potential to change following current injection.
The membrane potential at rest is -65 mV.

a) You inject enough current to depolarize the axon by 5 millivolts and you record the membrane
potential as -60.7 mV after 8 milliseconds. What is the time constant (τ1) of this axon?

b) When you depolarize the axon sufficiently to produce an action potential you find the membrane
potential changes much more rapidly during the rising phase of the action potential than it does with
a subthreshold depolarization. The membrane depolarizes from threshold (-50 mV) to the peak of
the action potential (let’s make it +50 mV) in a very short period – you find, for example, the
membrane potential goes from -50 mV to +45 mV in 0.6 milliseconds. What is the time constant of
this axon during the rising phase of the action potential?

c) What accounts for the much smaller τ we calculated for the rising phase of the action potential
(question 1a), as compared to the larger τ we calculated for the passive depolarization (question
1b)?

2) The figure above shows the flow of current down a myelinated axon, from a node of
Ranvier that ends at Point A to nodes that begin at Point B and Point C. The length of the
myelinated segments is 1 mm (1000 µm). The node itself is 100 µm long.

18
a) An action potential takes the membrane potential from resting membrane potential (-60 mV) to
the peak depolarization (+40 mV) at Point A. When you measure the membrane potential at Point
C you find it reaches only -55 mV. What is the length constant of the axon between Point A and
Point C?

b) What we just did for the length of axon between points A and C is not entirely kosher because
each segment of the axon – the two myelin segments and the node – has its own λ. So let us figure
out the λ for a myelin segment. You record from the node at B after injecting 100 mV of current at
A and you find the membrane potential at B goes from -60 mV to -23 mV. What is λ for the myelin
segment between A and B?

c) Let’s assume the myelin segment between B and C has the same λ as the myelin segment
between A and B. What, then, is the λ for the node of Ranvier?

3) Explain why demyelination of an axon produces a complete failure in action potential conduction
rather than just a slowing in action potential conduction velocity.

4) A dendrite of the neuron on the previous page has a λ equal to that of the myelinated segments of
its axon. But the dendrite is not myelinated, so what is about the dendrite that makes it λ so long?

5) The figure to the left shows that enough current has entered an axon to
depolarize it by 3 mV at the site of current injection (the line labeled 0.0).
The membrane potential goes from -70 mV to -67 mV. Two milliseconds
after the current begins, the membrane potential has reached -68.1 mV. When
will it reach -67.15 mV?

6) At one millimeter from the site of current injection the membrane potential
at its peak depolarization reaches -68.89 mV (the arrow on the line labeled
1.0). What will the membrane potential at its peak be three millimeters from
the current injection site?

19
 7) The large axons in this figure have only one
node in the distance covered by the
photomicrograph (arrows point to the nodes of two
such axons). Over that same distance a thinner,
more lightly myelinated axon has two nodes (this is
the axon between the two with arrows). All of that
is meant to say the following: nodes of narrow,
thinly myelinated axons are closer together than
nodes of wide, thickly myelinated axons. Use
electrical properties and membrane constants to
explain why the nodes for narrow, thinly myelinated
axons are so much closer to one another than the
nodes for wide, thickly myelinated axons.

8) You will notice in the figure above there are fifteen axons closely bundled together. Studies
estimate that if all 15 generated a train of action potentials [K+]o would rise from 3 mM to 6
mM if K+ were allowed to accumulate.

a) Explain why such an increase in an extracellular K+ would depolarize the axons (in other words,
why doesn’t the addition of positive charge outside the axons hyperpolarize them?).

b) Explain why this long-lasting depolarization would make it impossible for the axons to generate
action potentials.

c) If these are CNS axons, what is it that prevents [K]o from ever rising to 6 mM around a bundle of
axons (that is, what keeps K+ from accumulating in extracellular space)?

STUDY QUESTIONS - KEY

1) You record from an axon while injecting current through a microelectrode and you
measure how long it takes for the membrane potential to change following current injection.
The membrane potential at rest is -65 mV.

a) You inject enough current to depolarize the axon by 5 millivolts and you record the membrane
potential as -60.7 mV after 8 milliseconds. What is the time constant (τ) of this axon?

We can answer this the old-fashioned way by recognizing the change in voltage (ΔVm) at time
t = 4.3 mV and the absolute change is 5 mV. So Vt becomes 4.3 mV (the difference between
resting potential (-65mV) and the potential recorded at 8 milliseconds (-60.7 mV). And the
question tells you the amount of current injected will depolarize the membrane by 5 mV, so V!
= 5 mV.

20
Vt = V! (1-e-t/ )
τ
4.3 = 5 (1-e-8/ )
τ
4.3/5 = 1-e-8/ τ
0.14 = e-8/ τ

ln 0.14 = -8/τ
1.97 τ = 8
τ = 4 ms

Or you can look at the percent change in Vm and recognize from it how many τ we are dealing
with. A 4.3 millivolt depolarization is 86% of the eventual total depolarization of 5 millivolts.
That 86% change = 2 τ in 8 milliseconds, so that make 1 τ = 4 milliseconds.

b) When you depolarize the axon sufficiently to produce an action potential you find the membrane
potential changes much more rapidly during the rising phase of the action potential than it does with
a subthreshold depolarization. The membrane depolarizes from threshold (-50 mV) to the peak of
the action potential (let’s make it +50 mV) in a very short period – you find, for example, the
membrane potential goes from -50 mV to +45 mV in 0.6 milliseconds. What is the time constant of
this axon during the rising phase of the action potential?

With 95% of the total depolarization (3 τ) in 0.6 milliseconds, τ = 0.2 ms

If you wanted to calculate this, you would use 100 mV (the total depolarization from -50 mV
to +50 mV) as V!; you would use 95 mV (the depolarization from -50 mV to +45 mV) as Vt.
And t = 0.6 ms.

ln 0.05 = -0.6ms/τ 3 τ = 0.6ms τ = 0.2ms

c) What accounts for the much smaller τ1 we calculated for the rising phase of the action potential
(question 1a), as compared to the larger τ1 we calculated for the passive depolarization (question
1b)?

Two electrical properties, Cm and Rm, go into determining τ1 . Cm is a constant for any piece
of membrane – it is does not change from one moment to another – whereas Rm does change
as the number of open channels varies. As channels open, Rm decreases and, therefore, τ
shrinks. That’s what happens during the rising phase of an action potential: many voltage-
gated Na+ channels open, Rm decreases and τ shrinks.

21
2) The figure above shows the flow of current down a myelinated axon, from a node of
Ranvier that ends at Point A to nodes that begin at Point B and Point C. The length of the
myelinated segments is 1 mm (1000 µm). The node itself is 100 µm long.

a) An action potential takes the membrane potential from resting membrane potential (-60 mV) to
the peak depolarization (+40 mV) at Point A. When you measure the membrane potential at Point
C you find it reaches only -55 mV. What is the length constant of the axon between Point A and
Point C?

The amount of current that enters at node A is 100 mV (depolarization from -60 mV to +40
mV) but only 5% of that current remains at node C (a 5 mV depolarization from -60 mV to -
55 mV). That means 95% of the current has leaked out, which translate to a length equal to
three λ . The total distance between and C is two myelin segments (1000 µm long each) and
node B (100 µm long) = 2100 µm. 2100 µm for 3 λ means 1 λ = 700 µm. Or you could use the
equation for calculating λ and get the following:

Vx = Vo (e-l/ ) 5 = 100 (e-2100/ )

λ λ
ln 0.05 = -2100/λ -3λ = -2100 λ = 700 µm

b) What we just did for the length of axon between points A and C is not entirely kosher because
each segment of the axon – the two myelin segments and the node – has its own λ. So let us figure
out the λ for a myelin segment. You record from the node at B after injecting 100 mV of current at
A and you find the membrane potential at B goes from -60 mV to -23 mV. What is λ for the myelin
segment between A and B?

The change in membrane potential at node B is 37% of that produced at node A – and so this
distance covered by one myelin segment is equal to 1 λ . And since the myelin segment is 1 mm
long (1000 µm), the λ for the myelin segment is 1000 µm.

c) Let’s assume the myelin segment between B and C has the same λ as the myelin segment
between A and B. What, then, is the λ for the node of Ranvier?

Let us figure out what we know already. The total length of axon from node A to node C is an
aggregate of 3 λ . The distance covered by each of the two myelin segments equals 1 λ . So that
leaves a distance equal to 1 λ for the node and that node is 100 µm long. The λ for the node is
100 µm.

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3) Explain why demyelination of an axon produces a complete failure in action potential conduction
rather than just a slowing in action potential conduction velocity.

Action potentials fail because voltage-gated Na+ channels in a myelinated axon are present
only at the nodes; current that flows from one node to the next must be able to open those
channels at each successive node. With the reduction in Rm because of demyelination, the
amount of current that reaches from one node to the next is not enough to depolarize the
membrane of the second node to threshold.

4) A dendrite of the neuron on the previous page has a λ equal to that of the myelinated segments of
its axon. But the dendrite is not myelinated, so what is about the dendrite that makes it λ so long?

Internal resistance (ri) and membrane potential (rm) determine λ . A low ri requires a
dendrite with a large radius, so the dendrite could be wide to produce a long λ. A high rm
requires either myelination – which is something dendrites do very, very rarely – or a plasma
membrane with very few open channels. Keeping very open channels in the dendrite’s
membrane would also lengthen its λ.

5) The figure to the left shows that enough current has entered an axon to
depolarize it by 3 mV at the site of current injection (the line labeled
0.0). The membrane potential goes from -70 mV to -67 mV. Two
milliseconds after the current begins, the membrane potential has reached
-68.1 mV. When will it reach -67.15 mV?

After two ms, the membrane is depolarized by 1.9 mV (from -70 to -

68.1 mV); that is 63% of the final value (3 mV), which means 1 τ = 2
milliseconds. When it reaches -67.15 mV it will have gone 95% of the
way toward the final value. That is 3 τ. So it will take 6 milliseconds
(3 times τ) to get to -67.15 mV.

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6) At one millimeter from the site of current injection the membrane potential at its peak
depolarization reaches -68.89 mV (the arrow on the line labeled 1.0). What will the membrane
potential at its peak be three millimeters from the current injection site?

The drop from a 3 mV depolarization to 1.11 mV depolarization is a reduction by 63%. That

means 1 mm = 1 λ ; therefore 3 mm = 3 λ , with a 95% reduction in depolarization. Five
percent of 3 mV equals 0.15 mV. The membrane potential at its peak will be only 69.85 mV.

7) The large axons in this figure have only one

node in the distance covered by the
photomicrograph (arrows point to the nodes of
two such axons). Over that same distance a
thinner, more lightly myelinated axon has two
nodes (this is the axon between the two with
arrows). All of that is meant to say the
following: nodes of narrow, thinly myelinated
axons are closer together than nodes of wide,
thickly myelinated axons.

Use electrical properties and membrane constants

to explain why the nodes for narrow, thinly
myelinated axons are so much closer to one
another than the nodes for wide, thickly myelinated
axons.

Lambda is the key to this distance. There must be enough current moving from one node to
the next node to bring its membrane to threshold. Narrow axons have higher internal
resistance and thinly myelinated axons have lower membrane resistance. The result is a
shorter λ and the need to move nodes closer together. Notice the question explicitly mentions
thin and unmyelinated to talk about an axon with closely spaced nodes, and so it invites an
answer that addresses both internal resistance and membrane resistance. And also notice the
answer includes not one word about τ . That omission is essential because τ plays NO ROLE AT
ALL in the spacing of nodes.

8) You will notice in the figure above there are fifteen axons closely bundled together. Studies
estimate that if all 15 generated a train of action potentials [K+]o would rise from 3 mM to 6
mM if K+ were allowed to accumulate.

a) Explain why such an increase in an extracellular K+ would depolarize the axons (in other words,
why doesn’t the addition of positive charge outside the axons hyperpolarize them?).

The greater [K]o has shifted EK to a less negative value (-83 mV; Nernst would give you that
figure) and that change in EK has reduced the outward driving force on K+. You can then

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either use GHK to determine the effect or recall that resting membrane potential is fueled
principally by K+ efflux. Reduction in that efflux drives the membrane potential into
depolarized territories (to about -52 mV). BTW, this answer contains a very handy number to
store in long-term memory; a doubling in the extracellular concentration of an ion produces an
18 mV change the equilibrium potential for that ion.

b) Explain why this long-lasting depolarization would make it impossible for the axons to generate
action potentials.

With resting membrane potential so depolarized, the inactivation gates of voltage-gated Na

channels would not reopen; the axons would be in permanent absolute refractory periods.

c) If these are CNS axons, what is it that prevents [K]o from ever rising to 6 mM around a bundle of
axons (that is, what keeps K+ from accumulating in extracellular space)?

Astrocytes are K+ sinks – the ion flows out of extracellular space and into the cytosol of the
surrounding astrocytes.

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