Neurophysiology – lecture 11

February 15, 2011

1 Review:
1. We have been formulating Biophysical Models to explain resting potentials.
2. Each model is based on a set of assumptions.
For Model II these are:
(a) There are ion concentration differences across the cell membrane.
(b) Only concentration and voltage gradients drive ions.
(c) The cell membrane is permeable to only 1 ion, in this case that ion is K+.
(d) The net ionic flux across the membrane is 0.
3. From these assumptions one can derive the Nernst Equation.

RT [K+ ]o
Vm = ln + (1)
zF [K ]i

[D+ ]o
At 25◦ C Vm = 59 mV log (2)
[K+ ]i

4. This equation predicts that as the [K+ ]o increases by a factor of 10 the transmembrane potential will
increase by 59mV. This provides an effective means by which to determine if the Nernst Equation and
the assumptions on which it is based describe the state of the membrane under study.
5. Similar Nernst Equations can be formulated for Na+ and Cl− .
6. However, the Nernst equation for K+ does not adequately fit the resting potential data recorded from
frog muscle (Figure 7A).
7. Therefore, we adopt a third set of assumptions:
1), 2) and 4) assumptions are the same.
3) PK > PNa , PCl are all > 0, while PA = 0.
8. From these assumptions one derives a Qualitative Model in which the flux arrows for diffusion down
each concentration gradient can first be drawn in since the concentrations of the various ions is known
both inside and outside the cell.
Since PK > PNa , PCl , the flux of K+ down its concentration gradient will be greater than that of either
of the other 2 ions.

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 Since Cl− is negatively charged, its ionic current will be in the direction opposite to that of its flux.
Since we are concerned with the movement of charge, we convert all ionic fluxes into currents,
The resulting currents are dominated by the large outward current carried by K+ hence there is a net
+ charge leaving the cell and the inside becomes negative relative to the outside.
This inside negativity will become larger as more + charge leaves the cell. Eventually, the inside
negativity will produce inward currents driven by the voltage gradient that are large enough to equal,
but be oppositely directed, to the outward currents produced by the concentration gradients. At this
point there will be no net ionic current and dV
dt will = 0 and the membrane will show a steady potential.

9. From this third set of assumptions we can derive:

PK [K+ ]o + PNa [Na+ ]o + PCl [Cl− ]i

 
RT
Vm = ln (3)
zF PK [K+ ]i + PNa [Na+ ]i + PCl [Cl− ]o

10. This equation is called the Goldman-Hodgkin-Katz (G-H-K) Equation and it can fit the data given in
Figure 7B as well as other resting potential data.
11. The resting potential data from squid axons is well fit when:
PK : PNa : PCl
1 : 0.04 : 0.45

2 What do we learn from the G-H-K Equation?

1. If we divide the numerator and denominator in the fraction of the G-H-K Equation by PK and so
generate a number of terms multiplied by the ratio: PPNa
K
or PPNa
K
.
If PK gets very large each of the terms multiplied by these ratios becomes very small and the G-H-K
Equation shrinks to the Nernst Equation for K+ = EK .

RT [K+ ]o
Vm = ln + (4)
zF [K ]i

2. Similarly, if we divide the fraction in the G-H-K Equation by PNa or PCl and then make these perme-
abilities large, we get the Nernst Equation for Na+ or the Nernst Equation for Cl− .
3. Since EK ≈ −90 mV, ENa ≈ +50 mV, and ECl = −40 mV, these calculations show that the G-H-K
Equations says that the transmembrane potential can never exceed +50mV or go lower than -90mV.

3 The relationship between the various models we have discussed

1. We have outlined a Single Channel Model, Models for the Cell Membrane and Biophysical Models.
Are they separate or should they be combined in some way?
2. The Single Channel Model characterized the single channel as a simple resistor. On the I − V plot
∆I
of currents going through a single channel, the slope of the line, , was a constant in accord with
∆V
∆I
Ohms Law and ran through the origin of the graph. The channels conductance, G = . To avoid
∆V
confusion with other uses of G, the single channel conductance is referred to as γ and the single channel
current as i.

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 3. In the past cases we dealt with cases where the solution inside the patch electrode and outside the
patch electrode were the same, so there was no diffusion across the membrane patch and hence no
voltage across the membrane patch either unless the experimenter imposed a voltage across the patch.
4. But if the ionic concentration inside the patch electrode and outside it are different and the if the ion
channel in the patch of membrane can pass ions whose concentration is different on either side of the
membrane, then a transmembrane potential will develop as we have seen with cell membranes. Since
many channels are ion selective, this potential will be based on the concentration difference of the ion
for which the channel is selective, i.e., it will be the equilibrium potential, Ei , of that ion.
5. When the voltage across the patch equals Ei , then there will be no current carried by the ion in question
across the membrane. In other words Ei will move the line describing the amount of current obtained
at various membrane voltages laterally along the voltage axis. The offset line will be described by
i = γ(Vm − Ei ).
6. Several class periods ago I left you with a choice as to which of 3 Cell Membrane Models best described
the data obtained from cell membranes. In this case a “good” model should
(a) be able to produce a resting potential and
(b) predict an exponentially changing Vm when a rectangular current pulse is passed through it.
Both the model that placed the battery in series with the RC circuit and the model that placed the
battery in the current arm with the resistor satisfy both criteria.
But only the later model is used as a model of the cell membrane because there is nothing physically
present which could correspond to a battery being in series with the RC portion of the membrane.
7. The third class of models we have dealt with are Biophysical Models used to explain the source of
“steady potentials”.

4 The relation of the single channel model to the Electrical Model

of the cell membrane
1. We note that there are hundreds to thousands of channels in each square micron of membrane and
that these include different channels selective for different ions.
That is there are channels for which the equation: iK = γ(Vm − EK ) applies, some for which : iNa =
γa (Vm − ENa ) applies and some for which: iCl = γCl (Vm − ECl ) applies.
2. All of these channels are independent of one another and are “in parallel” with one another. Being
in parallel means that the currents passed by the K+ selective channels will add (according to Kirch-
hoffs Current Law) to equal the total IK passing through the membrane. Likewise, the sum of the
currents passing through the Na+ selective channels will add to equal the total INa passing through
the membrane. And the same goes for the Cl− selective channel current.
3. Since many iK sum to IK and many γK sum to GK (conductances in parallel add),
IK = GK (Vm − EK ) and likewise
INa = GNa (Vm − ENa ) and likewise
ICl = GCl (Vm − ECl )
4. Assuming only these 3 currents cross the membrane, then we can show this in a Electric Membrane
Model which has 3 parallel pathways crossing the membrane in addition to the pathway which contains

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 the capacitor. These parallel pathways indicate that these 3 sets of ion channels are independent of
one another. In words this is referred to as the Independence Principle.
5. In the Electrical Model each of these 3 parallel pathways contains a resistor and a battery in series.
Current, say IK flowing through the resistor RK produces a voltage change = IK · RK . This voltage
change is in series with the Vb of the battery and therefore adds to it to equal the voltage difference
found across the entire membrane Vm . That is, Vm = IK · RK + Vb .
6. Rearrange this equation to: IK · RK = Vm − Vb , and substitute: IK = GK (Vm − Vb ).
7. But IK = 0 when Vm = EK , so the above equation which says IK = 0 when Vm = Vb indicates that Vb
must equal EK . Thus, IK = GK (Vm − EK ).
8. And INa = GNa (Vm − ENa ) and ICl = GCl (Vm − ECl ) following the same logic.
9. In conclusion, the Electric Membrane Model with the 3 ion specific parallel pathways comes to exactly
the same formulation of what controls transmembrane currents as does the Single Channel Model. (As
noted in step 3) above.)