Resting Membrane Potential

1. Neurons encode information as changes in the

membrane potential (Vm).

2. These are generated by opening and closing of ion

channels, which cause ions to flow down their
electrochemical gradients.

3. What is the nature of these gradients and how to they

influence Vm?

Membrane Hypothesis (1902, 1912):

Resting membrane potential: Arises from

high resting selective permeability to K+ and a
concentration gradient for K+ ions across the
membrane.

Action potential: Is produced by a transient

change in the membrane such that it loses its
exclusive permeability to K+ ions and becomes
permeable to all ions (membrane breakdown).

Hypothesis predicts that changes in K+ ion concentrations

should alter the resting membrane potential.
 A Model Cell

• Must be electroneutral (equal - and + charges).

• Osmotically balanced.
• No net movement of ions.

Equilibrium of a membrane permeant to one ion (K+)

Determined by 2 opposing forces: Chemical

vs. Electrical gradients at equilibrium
Nernst equation takes into account both forces.

The Nernst Equation

•Determined in 1888 from basic thermodynamic principles.

•Restates concentration gradient in electrical terms.

RT " [IonOut ] %
E Ion = ln$ '
zF # [Ion In ] &
Electrical Chemical

R = Gas constant (8.31 J/K.mol)

! T = Absolute temperature (K)
z = Valence of ion
F = Faraday constant (96,485.34 C/mol)

E = Vm at which there is no net movement of ions and at

which membrane will be drawn to when channels are open
 Calculating EK

RT " [KOut ] %
EK = ln$ '
zF # [K In ] &

RT/F = 25 mV at 25°C, so….

# [K ] & # [K ] &
EK !
= 25 " ln% Out ( E K = 58 " log% Out (
$ [K In ] ' $ [K In ] '

! !

# [K ] &
E K = 58 " log% Out (
$ [K In ] '
# [3mM] &
E K = 58mV " log% (
$ [90mM] '
!
E K = "85.7mV
!

•What happens if we raise K

!out by 3 mM?

•How much do we need to change Kin to get an

equivalent change in Vm?

Kout (mM) Vm (mV)

2 -133
10 -92
20 -75
200 -17

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 Experimental support for membrane hypothesis

Kout (mM) Vm (mV)

2 -133
10 -92
20 -75
200 -17

Predicted Vm
Measured Vm
Why is measured Vm different than
predicted Vm?
Hodgkin and Keynes 1954

Calculating Vm for membranes permeable to multiple ions

Goldman-Hodgkin-Katz (GHK) equation: Weighted average of Nernst potentials
for multiple ions, using relative permeability as weighing factor.

# p [K ] + pNa [NaOut ] + ....&

Vmrest = 58 " log% K Out (
$ pK [K In ] + pNa [Nain ] + .... '

•If pNa = 0, then Vm = EK (-75 mV) ENa

! 55 mV
•If pK = 0, then Vm = ENa (+55 mV)
•If pK = pNa, then Vm=somewhere -19mV
between ENa and EK (-19 mV) -75mV
EK

For permeant anions (z<0) like Cl(-), invert out and in:

# p [K ] + pNa [NaOut ] + pCl [Clin ] &

Vmrest = 58 " log% K Out (
$ pK [K In ] + pNa [Nain ] + pCl [Clout ] '
Calculate Vm, using concentrations shown in the table,
assuming relative permeabilities of:
! PK:PNa:PCl = 100 : 4 : 45

Ion Out In What happens if you

increase PCl 5-fold?
K+ 10 200
Na+ 88 10
Is Chloride playing a major
Cl- 112 12 role in setting Vm?
 GHK equation can be restated as conductances:

I=V/R=Vg At Vrest INa = -IK so…

INa=gNa(Vm-ENa) gNa(Vm-ENa) = -gK(Vm-EK)

IK=gK(Vm-EK)

gK E K + gNa E Na
Vm =
gK + gNa
At rest the cell is at a steady state and there is no
net current, however individual ions are still in flux.

!
Why doesn’t concentration gradient eventually run out?

Ion pumps maintain concentration gradient.

Na-K ATPase - exchanges 3Na to 2 K: electrogenic

and will contribute ~ -5 mV to Vm. Because of this,
at Vrest, IK is not equal to INa. Rather, IK is 1.5 times
more than INa in order to counter effect of pump.

Membrane can be modeled as an electrical circuit

No ATPase (model cell)

With ATPase
(real cell)
 Key Concepts
1. Resting membrane potential is determined
by selective membrane permeability to
specific ions at rest.

2. K+, Na+ and Cl- are the main determinants

of the RMP. Their gradients are maintained
by use of pumps and exchangers.

3. The GHK equation is a weighted average of

the equilibrium potentials of permeant ions,
where relative permeability is the weighing
factor.

Membrane Hypothesis (1902, 1912):

Resting membrane potential: Arises from

high resting selective permeability to K+ and a
concentration gradient for K+ ions across the
membrane.

Action potential: Is produced by a transient

change in the membrane such that it loses its
exclusive permeability to K+ ions and becomes
permeable to all ions (membrane breakdown).

Is this true? How would you test this?