Neurophysiology – lecture 9

February 3, 2011

1 Review:
1. Figure 6A shows that a rectangular current pulse through the membrane of a cell produces an expo-
nentially changing ∆Vm .
2. A circuit composed of a resistor and capacitor in parallel can be used to reproduce this pattern of
exponentially changing ∆Vm .
3. Mathematically, this waveform can be fit with the following equation:
−t
∆Vm = ∆Vrest + I · Rin (1 − e τ ) where τ = Rin · Cin (1)

which has been derived from Electrical Model.

4. One can evaluated Cin by:
(a) determining I · Rin from the maximum change in ∆Vm produced by the current
(b) then drawing a line parallel to the abscissa at 0.632(I · Rin )
(c) where this line crosses the ∆Vm line the indicated time will equal τ
(d) then since τ = Rin · Cin and Rin is known, Cin can be determined.
1F
5. Cm = specific membrane capacitance = Cin /Area of the cell = cm2 (with variance ranges from 0.5 to
2.0).
6. From having a value for Cm allows us to determine:
(a) that cell membranes behave electrically as if they were only 4.1-5nm thick (which fits with the
electron microscopists findings).
(b) only about 10−12 moles of anions/cm2 are needed to produce an intracellular voltage relative to
ground as large as -100 mV.

2 What aspect of the electrical behavior of cell has not been cov-
ered?
1. What is missing from our Electrical Model of a cell? Something to produce the ∆Vrest equal to -40 to
-100 mV.

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3 What is the source of this ∆V rest ?
1. Possible sources of ∆Vrest are:
(a) a transmembrane ion pump using ATP,
(b) a redox chemical reaction like Pb + S02−
4 → PbS04 + 2e− ,
(c) K+ channels.
2. The first 2 alternatives involve chemical reactions which can be recognized from physical processes like
diffusion because they are temperature dependent.
3. Temperature dependence can be characterized by a parameter called the Q10 .

reaction rate at T + 10◦

Q10 = (2)
reaction rate at T ◦

For chemical reactions Q10 = 2-3; for physical processes Q10 = 1.1-1.3. (Thus people had trouble
starting their cars this cold morning because the temperature was about −10◦ C below freezing and
hence the chemical reaction in the cars battery was occurring at only half the rate it would occur at
32◦ F and only one quarter the rate it would occur on a mild Spring day.)
4. On the other hand the milestone experiments on squid axons were done in a bath filled with sea
water at 4◦ C just a little bit above freezing and yet normal resting potentials and other voltages were
recorded, indicating they are dependent on diffusion, a physical process.
5. A simple experiment I ran yesterday indicates how diffusion can generate voltage differences in the
millivolt range. I placed a microelectrode full of 0.5M KCl into a bath of pond water and recorded a
voltage of -2mV between the inside of the electrode and the grounded bath.
I then replaced that microelectrode with another filled with 1M Potassium Citrate and placed that
microelectrode into the pond water and recorded a voltage difference of -40mV between the inside of
the microelectrode and ground. These experimental results are explicable when one learns that the
ability of these ions to move in water (called the relative ionic mobility, µi ) falls in the following ratios:
K+ = 1.00 Cl− = 1.039 Citrate3− = 0.318
Thus, K+ and Cl− diffused out of the microelectrode at about the same rate so what remained in the
microelectrode was about electrically neutral.
On the other hand K+ diffused out of the microelectrode more rapidly than Citrate3− , so the interior
of the microelectrode retained an excess of negative charge which is what was measured.
6. Thus, voltage differences can be produced by the diffusion of ions if:
(a) the ionic mobility of the cations involved and anions involved is different and
(b) if there are ion concentration differences to produce ion diffusion.

4 The definition of permeability

1. In the case of cell membranes, the ability of an ion to diffuse through the membrane is not determined
by its ionic mobility in solution but rather by its movement through whatever ion channels are present
in the membrane.

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 2. The ability of ions and nonionic compounds to pass through biological membranes is described as their
permeability. Permeability is a concept only used in biology.
3. Let us assume a fluid container separated into 2 compartments by a barrier of thickness ∆x. Say the
concentration of solute in the left hand compartment, c1 , is higher than the concentration of solute in
the right hand compartment, c2 .
−c2
4. Then c1∆x is called the concentration gradient and would be a positive number when moving from
∆c
the right to the left side of the container. The concentration gradient can also be designated as ∆x or
dc
dx .

5. On the other hand the solute will be diffusing “down the concentration gradient”. This diffusion will
produce a “flux” (designated J) of solute moving from the left side of the container to the right side
of the container. That is the direction of the flux is opposite to the direction of the concentration
gradient, but the magnitude of the flux is proportional to the magnitude of the concentration gradient.
c1 −c2
Mathematically, this means J is proportional to ∆x .
As usual this proportionality statement can be converted into an equation by introducing a constant.
In biology this constant is assumed to apply to cell membranes. This constant is called the Permeability
Coefficient, Pi . Different ions and different solutes have different Pi s. So, Ji = −Pi (c1 − c2 ).
6. We will be talking about PK , PN a , PCl , etc.

5 Models of how resting potentials are produced

1. These models are not Electrical Models but rather Biophysical Models based on principles generated
in physical chemistry.
2. To generate a model,
(a) we begin by making a set of assumptions.
(b) then we determine what outcomes will be the result of this set of assumptions
i. we determine these outcomes first qualitatively
ii. then we determine the outcomes quantitatively.
(c) if the outcomes do not match what is actually observed, we go back to the drawing board and
formulate a better set of assumptions.

6 First Resting Potential Model

1. The first set of assumptions:
(a) There are differences in ion concentrations across the cell membrane.
dc dv
(b) Only concentration gradients, dx , and voltage gradients, dx , drive ions through the membrane.
+ + − −
(c) The membrane is permeable to K , Na , Cl , and A .
(d) Outcome of these assumptions:
JK = −PK (c1 − c2 ) = −PK (3 mM − 150 mM) = −PK (147 mM)
JN a = −PN a (c1 − c2 ) = −PN a (152 mM − 3.2 mM) = −PN a (148.8 mM)

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 Since PK approximately = PN a , JK and JN a are approximately equal but are oppositely directed,
so the net J will be approximately 0. This would also be true for the anion fluxes.
With no net ionic flux there will be no ions to charge up the membrane and ∆Vm is approx. 0mV.
2. Since this outcome disagrees with what is observed, back to the drawing board.

7 Second Resting Potential Model

1. The second set of assumptions:
(a) There are differences in ion concentrations across the cell membrane.
dc dV
(b) Only concentration gradients, dx , and voltage gradients, dx , drive ions through the membrane.
+
(c) The membrane is only permeable to K . The permeability of the other ions is 0. (In this case
the membrane would be called a “semipermeable membrane”.)
2. Qualitative outcome of these assumptions:
(a) Let JdK represent the flux of K+ driven out of the cell by the concentration gradient for K+ .
(b) Let JeK represent the flux of K+ driven into the cell by the voltage gradient.
(c) Assuming the ion concentrations given previously, there will be a much higher concentration of
K+ inside the cell than outside of it. Since K+ can permeate the membrane, there will be a JdK
out of the cell.
(d) However, since PA cannot permeate the membrane, as K+ leaves the cell and A− stays inside,
there will be a slight excess of negative charge on the inside developing on the inside of the
membrane.
(e) This slight intracellular negativity will attract K+ to the inside of the cell and thus a flux of K+
driven by the voltage gradient, JeK , will develop. This flux will be small at first since the voltage
gradient will be small.
(f) As long as JdK is larger than JeK there will be a loss of K+ from the inside of the cell and hence
the intracellular voltage will become more negative relative to the voltage outside the cell. This
will mean that JeK will become larger.
(g) Eventually, the transmembrane voltage will become sufficently negative relative to the outside
voltage that JeK into the cell will equal JdK out of the cell. At this point there will be no net K+
flux and the transmembrane voltage will be steady!
(h) So this model makes the qualitative prediction that there will be a resting potential established.