Neurophysiology – lecture 12

February 17, 2011

1 Review:
1. We derived the Goldman-Hodgkin-Katz Equation for cases where PK , PNa , PCl are greater than 0 and
dVm
=0
dt
2. This equation predicts the resting and other steady potentials;

PK [K+ ]o + PNa [Na+ ]o + PCl [Cl− ]i

 
RT
Vm = ln (1)
zF PK [K+ ]i + PNa [Na+ ]i + PCl [Cl− ]o

3. With the right choice of PK , PNa and PCl the data obtained from most resting potential studies can
be fit nicely with this equation, (See Figure 7 B.)
4. In a Qualitative Model this means that there will be a:
large Iout carried by K+ and driven by diffusion and a smaller Iout carried by Cl− and driven by
diffusion which is balanced by:
smaller Iin carried by K+ and driven by the voltage gradient +
an even smaller Iin carried by Na+ driven by diffusion +
a small Iin carried by Cl− driven by the voltage gradient +
a small Iin carried by Cl− driven by the voltage gradient.
5. From the G-H-K Equation we learned the if its predictions hold true then dVm will always be between
EK (about -90mV) and E Na (about +50mV). 6) In January we saw that Single Channels behave as
simple resistors between the outside and inside of the cell membrane.
6. If the ionic concentrations on either side of the membrane are not the same then there will be a
transmembrane potential, Vm , across the membrane. This Vm = the equilibrium potential Ei of
the ion for an ion specific channel. Therefore, the electrical model of a channel contains a resistor
(conductance) and battery = Ei in series across the membrane. This means iK = γK (Vm − EK ) for
K+ -channels, with a similar equation describing ion currents through the other types of channel.
7. Assuming there a many, many K+ channels near one another in a patch of cell membrane, the total
IK through that patch of membrane will be the sum of all the iK for the channels in that patch of
membrane. Likewise, since conductances in parallel add algebraically, GK for that patch of membrane
will be the sum of the gK of all the ion channels in that patch of membrane.
So for that patch of membrane, IK = GK (Vm − EK ), describes the total current carried by K+ ions
through the membrane.

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 And similar equations based on the current carried through ion specific channels can be generated:
ICl = GCl (Vm − ECl ) and INa = GNa (Vm − ENa )
8. In an Electrical Model for a patch of cell membrane this means that there are 3 ion paths through
the membrane with each path having an ion specific conductance, Gi , and a battery with a voltage
equal to Ei in series between one side of the membrane and the other. However, for an entire patch
of membrane one must also consider that the membrane has capacitance and hence add another
transmembrane current path with a capacitor in it.
9. This Electrical Model can be simplified further by noting that the 3 conductances in parallel can be
added together to obtain an equivalent membrane conductance and the 3 batteries will collectively
provide the transmembrane potential or resting potential since we are describing situations in which
dVm
= 0.
dt

2 A Note
1. Note that in all recordings from single channels we find they are not open all the time, but rather open
and close - i.e., allow ions to pass through them or not.
2. Thus, it is improbable that all channels in a patch of membrane will be open at the same time. To
take this into account we define a parameter, Po , the probability of a channel being open.
3. Then IK = n Po iK , where n = the total number of K+ channels in the membrane patch.

3 Relating the Electrical Cell Membrane Model to the Biophysical

Model
dVm
1. Starting with the Cell Membrane Model with 3 separate ion channels and assuming = 0, it is
dt
evident by Kirchhoffs Current Law that any for current, IT , being passed through that membrane:
IT = IK + INa + ICl .
dVm
2. But for steady potentials, = 0, so IT = 0 and IK + INa + ICl = 0.
dt
3. Substituting for these currents we get:

GK (Vm − EK ) + GNa (Vm − ENa ) + GCl (Vm − ECl ) = 0 (2)

Multiplying through and collecting terms we get:

Vm (GK + GNa + GCl ) − GK EK − GNa ENa − GCl ECl = 0 (3)

4. This equation can be rearranged to:

n
X
Gi Ei
GK EK GNa ENa GCl ECl i=1
Vm = + + = n (4)
GK + GNa + GCl GK + GNa + GCl GK + GNa + GCl X
Gi
i=1

5. This equation is referred to as the Parallel Conductance Equation.

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 6. Note that in formulating this equation, it is assumed that:
(a) There are ionic concentration differences across the membrane; hence the use of the Nernst Equa-
tion and equilibrium potentials.
(b) Only concentration and voltage gradients drive ions through the membrane.
Again this assumption is incorporated into the use of the Nernst Equation.
(c) K+ , Na+ and Cl− are assumed to be permeable since there is an ion channel for each of them.
dVm
(d) = 0 in the assumptions above.
dt
(e) The channels for the flow of the 3 ions are assumed to be independent of one another which is
represented in the model membrane circuit by having 3 separate pathways - one for each ion.
Also Note that these assumptions are the same assumptions that one makes to derive the G-H-K
Equation.
7. Relating the parameters in the Parallel Conductance Equation with those in the G-H-K Equation.
The Electrical Model The G-H-K Equation
Uses currents, I (coul./sec) Uses fluxes, J (moles/sec)
so I = z F J, where z = the
ions valence and F is Fara-
day’s constant
Uses Ei Also uses Ei
Uses Gi Uses Pi
Gi and Pi differ in that Pi is an Intrinsic Membrane property and will have a value whether or not
there are ions, i , around to permeate the membrane.
Gi on the other hand will be 0 if there are no ions, i, around to carry current through the ion specific
membrane ion channels.
However, both Gi and Pi are parameters that govern the movement of ions through membranes and
there is an equation that directly relates them.

4 Uses of the Parallel Conductance Equation

1. This equation simplifies the calculation of steady potentials.
2. Assume GNa = 1 and GK = 9 and GCl = 0, then
n
X
Gi Ei
i=1
Vm = n = 0.9 EK + 0.1 ENa = −76 mV1 (5)
X
Gi
i=1

5 Problems with these Models

1. What is the most membrane permeant ion? H+ And we havent even mentioned it? Why?
1 There is some serious math missing here.

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2. Considering J = PH ([ ]in − [ ]out ), the equation which governs concentration gradient fluxes, we see
that [H+ ] is on the order of 10−7 M, while [K+ ] or [Na+ ] is on the order of 100x10 − 3 M = 10−1 M.
So H+ are exceedingly small compared to K+ or Na+ fluxes and can be ignored.
3. Considering the Qualitative Model of the cell membrane when assuming K+ , Na+ and Cl− are all
permeable, we note a problem. At resting potential Na+ is driven into the cell by both the concentration
and voltage gradients, while there is a larger efflux of K+ down its concentration gradient than an influx
of K+ down the voltage gradient. Thus, Na+ should accumulate inside the cell and K+ should be lost
from inside the cell over time. Of course, this does not happen.
4. In the cell membrane there is a molecular mechanism referred to as the Na+ –K+ exchange pump. This
pump maintains the intracellular concentrations of Na+ and K+ by pumping Na+ out of the cell and
K+ into the cell. This is a pump and uses energy supplied by ATP to move these ions across the cell
membrane.
It is estimated that 20% of all the calories people consume are used by this pump to maintain intra-
cellular ion concentrations in all the cells in the body. Because ATP is being used to pump ions this
means of transmembrane transport is referred to as “active transport”.
5. The breakdown of each molecule of ATP to ADP results in the movement of 3 Na+ ions out of the cell
and 2 K+ ions into the cell. Since more + charge is pumped out of the cell than is pumped into the
cell, the pump acts to increase the intracellular negative charge, i.e., to make Vrest more negative. For
this reason the pump is said to be “electrogenic”.
6. There is some uncertainty about how large this change in membrane potential is. As an approximation
an increase in Vrest of -6mV is accepted by many authors. On the other hand increases in Vrest by as
much as -20mV have been recorded in some marine invertebrate neurons.
7. The membrane Na+ –K+ exchange pump counteracts the efflux of K+ and the influx of Na+ and
thereby maintains the intracellular concentration of these ions at a constant level. But it takes energy
to do this, so the so called “resting potential” maintained by this mechanism is referred to as a “steady
potential” to indicate that the potential is constant. This is distinct from an “equilibrium” which
we talked about with regard to the formulation of the Nernst Equation, because “equilibria” do not
require any energy source to maintain them.