Resting Membrane

Potentials

The Lipid Bilayer is a Capacitor

The electric signals of neurons arise from the

movement of charges in the form of ions across the
plasma membrane.
The membrane has 2 essential features:
1. The lipid bilayer is an impenetrable barrier to the
movement of ions across it. Ions can be stored within
the membrane within the leaky channels, thereby
actually occupying space among the phospholipid
tails. Thus, charge can be stored like an electrical
capacitor!
Thats because the membrane is leaky to ions,
depending on the number and type of leaky channels,
and this must be constantly corrected at the expense
of ATP.

2. The lipid bilayer has high charge storage

capacity because it is very thin, enabling the
stored charge to get VERY close to the
corresponding, but opposite charge, lowering
their potential energy.
. This separation of charges generates an electric
field or potential difference across the membrane,
given by V = Q/C or charge/capacitance.
. Your typical membrane has a capacitance of 1
F/cm2, about 70% of which is due to the lipid
bilayer and the rest because of embedded
proteins.

At Rest, the Neuron Membrane is Permeable to

K+, Na+ and ClEvidence from radioactive tracer studies reveals
that all major ionic species can pass through
the resting neuronal membrane; i.e., there are
leak channels for these ions
Outside

K+

Inside

K+

Na+

Na+

Cl-

Cl-

However, not all ionic species cross the membrane

at the same rate or to the same extent
1) Not all channels allow the same number of
ions to pass per unit time (i.e. carry the same
current), maybe due to structural differences
in the channels?
e.g1. The more narrow the channel the more difficult
it is for an ion to pass through the channel
(bumps into the wall, squeezes through, resulting
in decrease in the kinetic energy)
e.g2. There are different numbers of the different
channels in the membrane (i.e. there are more K+
leak channels than Na+ leak channels)

Permeability
A measure of how easy it is for an ion to cross the
membrane; takes into account ease to traverse a channel
or the number of channels, etc.
At rest, for giant squid axon
Pk+ : PNa+ : PCl- = 1 : 0.04 : 0.45
Ratios differ for different species and different cell types
within a species.
Here, PK+ is 25 x higher than PNa+. In other neuronal types,
in rat, this difference can be as high as 75 x greater.

The Basis of the Resting Membrane

Potential

rieb, E. Human Anatomy and Physiology, 5th ed.]

The Na+-K+ ATPase Coupled Pumps to

Counters the Resting Ionic Fluxes
At rest, the low level influx of Na + is balanced
by the low level efflux of K+.
This leak must be countered over the long term
by the ATP-coupled pumps that maintain the
ionic concentration gradients across the
membrane.

The ATP-coupled Pump is Electrogenic

1) At rest, the passive ion fluxes (due to
concentration gradients and Vm) are countered by
the active ionic fluxes (due to the ATP-coupled
pumps).
2) Consequently, Vm is constant at -60 mV and the K+
and Na+ concentration gradients are also constant
through time.
3) Since the pump moves more Na+ out of the cell
than it moves K+ into the cell, it contributes to the
Vm, i.e. it contributes to the net negativity inside
the cell.

Membrane potentials (Vm) = a voltage difference

between the intracellular and extracellular
fluids.
Vm is always negative inside relative to
outside.
Vm ranges from -40 to -200 mV, depending
on the type of cell.
Range of resting Vms for mammalian neurons
is -40 to -75 mV;
Any electrical signaling involves deviating
from the resting value.

 This equilibrium point arises when the ratio of the

P(finding an ion on the high-energy side (outside))
P(finding an ion on the low-energy side (inside))
= e-E/kT (i.e., Boltzmann Distribution).

The E for the ion is given by Q x Vm and because

concentrations probabilities, the result is the Nernst
Equation:
Vm = EK = (kT/ze)* ln{[K]o/[K]i}
Where e is the electronic charge and EK is the equilibrium
Nernst potential for K.
This can also be written as Ek = 58*log{[K]o/[K]i}
More on this later

 Vm results from the asymmetric distribution of

charges on either side of the plasma membrane
(more negative inside than outside).
However, most of the intracellular and extracellular
fluid are homogenously distributed (mixed, if
you will) on either side of the membrane, making
the bulk of the fluid electrically neutral.
Charge separation is achieved in small pockets or
clouds (~ 2 m) of charges spread over the surface
and attract each other on either side of the
membrane.

 For typical cellular values of [K]o & [K]I, EK+

~ -90 mV, which would be Vm, if the
membrane were permeable to only K+.
IMPORTANT! Only a very small fraction
only ~ 1ppm (10-6) have to leave the cell for
Vm to reach EK+ .

Electric Charges can arise within Membranes

in 2 ways:
1. Experimenters insert microelectrodes and
inject them.
2. Ion channels are open in the membrane.
e.g., K+ is the main ion that establishes the
resting membrane potential.
This channel is made up of 4 subunits
embedded within the membrane

How the Resting Membrane

Potential is Measured

Crystal Structure of the K+ Channel from above

and from the side

The K+ channel is structure such that a very narrow

tube through the inverted cone shape allows for only
50 H2O molecules and only 2 K+ in succession.

Because they strongly repel each other, when one enters

one will be forced out.

Two things determine the Voltage across the

Membrane
1. Selective passage of ions through ion channels.
2. [Ion]s may differ on either side of the membrane.
The membrane potential Vm tends to oppose
(further) diffusion of K+ since a negative Vm pulls
K+ back into the cell.
There is a balance between the disordering effect of
concentration and the ordering effect of Vm.
What is this balance?

There is also differential distributions of

different species of ions (biological charge
carriers) across the plasma membrane.
E.g., giant squid axon (Loligo)
Ion [Cytoplasm] [Extracellular Fluid]
(mM) (mM)
K+ 400 20
Na+ 50 440
Cl- 52 560
Organic- 385 0

Generalizations (although absolute

values differ across species and
among cells from the same
organism)
[K+]I (inside) > [K+]o (outside)
[Na+]I < [Na+]o
[Cl-]I < [Cl-]o
[Organic-]I > [Organic-]o

Recall this slide?

Resting Membrane Potential, Vm

rieb, E. Human Anatomy and Physiology, 5th ed.]

Thus, the unique permeability

characteristics of the plasma
membrane coupled with the original
K+ concentration gradient leads to
the establishment and
maintenance of the Vm without
expenditure of energy.

Use of the Nernst Equation to Calculate Theoretical

Vm for a Membrane Permeable Only to K +
E = RT/zF ln [ion]o(outside)/[ion]I(inside)
E = membrane potential (Volts)
R = gas constant (8.3143 joules/deg-mole)
T = absolute temperature (273o + oC); usually 20oC for
giant squid axon
z = valence, including charge and number
F = Faradays constant (96,490 coulombs/mole)

Simplifying the Equation

1) RT/zF reduces to 0.025 Volts or 25 mVolts at
20oC and a valence of +1 (K+ and Na+)
2) Thus, E (mVolts) = 25 ln [ion]o/[ion]I
3) Converting to log10 :
E (mV) = 25 x 2.3 log [ion]o/[ion]I
E (mV) = 58 log [ion]o/[ion]I

If the Nernst Equation is a Good

Model of Membrane Potential
Development, What Should
Happen if We Change [K+]o?
Predict Vm when [K+]o = [K+]I

Semi log plot of Vm versus [K+]outside, i.e. changing [K+]o changes

the concentration gradient across the membrane and the Vm that
develops in response to that gradient
0

Normal Vm
of -75 mV

Vm
(mV)
60

Normal [K+]o

4
-120

20

400
Log [K+]outside

 This is a common experimental technique used

when you want to stimulate (excite) (a)
neuron(s), say, in tissue culture or in brain
slices.
The addition of KCl to the bath or medium will
result in a depolarization (Why?).
However, as we will see when we cover action
potentials, the preceding slide is applicable only
up to T0, given the all-or-none nature of the AP.

What About Cl ?
-

1) Cl- permeability is relatively high

2) However, there is no active mechanism to
move Cl- across the membrane of most cells.
3) Consequently, Cl- passively distributes itself
across the membrane in relation to the Vm
established by Na+ and K+.

Vresting = 58 log [Cl-]I/[Cl-]o

Flipped
because of
negative
valence on
Cl-

Set by Na+ and

K+
Cl- passively distributes itself across the
membrane such that the concentration
gradient balances the Vm.
Net -

Net +
Concentration gradient

Cl-

ClElectrical gradient = Vm

A Modification of the Nernst Equation is

the Goldman-Hodgkin Equation can be
used to Predict Vm when the Membrane is
Permeable to Multiple Ions
PK + [K + ]o + PNa + [Na + ]o + PCl [Cl ]i

RT
Vm =
ln
F
PK + [K + ]i + PNa + [Na + ]i + PCl [Cl ]o

Vm theoretical = - 60 mV ~ the
empirically measured value in a resting
neuron

What happens to the Vm when leak

+
channels for Na and Cl are introduced
into the membrane?
Exercise #1 = Draw equilibrium in a resting
neuron. Start with a liver cell in equilibrium
and add Na+ leak channels to the membrane.
(Hint #1: See Time0+1 when Na+ is just starting
to enter the cell - the second image to follow
this slide). (Hint #2 : at equilibrium Vm = -60
mV and [K+]I>[K+]O and [Na+]I<[Na+]O

Explanation
1) Na+ enters the cell and depolarizes the membrane.
The rate of entry is low and is set by the # and
structure of the Na+ leak channels and the Na+
concentration gradient.
2) The Vm no longer balances the K+ concentration
gradient.
3) A small amount of K+ is now able to leave the cell.
4) At equilibrium, the rate of entry of Na+ is equal to
the rate of exit of K+ and the Vm is constant at a new
value of -60 mV; i.e. more + than for liver cell
equilibrium. At equilibrium there is no net
movement of charge.

Explanation (contd)
5) The Vresting is much closer to EK+ than ENa+
because the permeability of the membrane to
K+ is much greater than the permeability of
the membrane to Na+.

A Simple Neural Network to

Demonstrate Signaling within the
Nervous System Synapse = site of cell to cell

Presynaptic neuron = carries

communication in the nervous system;
information as an electrical
electrical signal gets converted to a
signal (action potential)
chemical signal (neurotransmitter) then
toward the synapse
back into an electrical signal

Postsynapti
c neuron =
carries
information
as an
electrical
signal away
from the
synapse

Membrane Potentials - to
recap:
A. All living cells have membrane
potentials (Vm) = a voltage
difference between the intracellular
and extracellular fluids; they are
always negative inside relative to
outside (convention in
neurophysiology); Vm ranges from -40
to -200 mV(olts) depending on the
type of cell; mammalian neurons
have a range of resting Vms from
-40 to -75 mV and electrical

Recording apparatus =
ohmmeter, amplifier,
oscilloscope or computer

1) Recording a Vm begin
with both electrodes in the
extracellular fluid
Intracellular electrode =
glass pipette drawn out to a
small tip diameter (~0.5
um); filled with highly
conductive KCl solution
KCl

Liver cell
= nonexcitable
cell

AgCl
electrode
s (wires)

KCl
Extracelluar
electrode =
larger glass
pipette also
filled with KCl
solution

+75
Vm

(mVolts)
0
2
Time (sec)

KCl

-75

Liver cell
= nonexcitable
cell

KCl

2) Recording a Vm impale
cell with intracellular electrode

B. Membrane Potentials Result from Differential

Distributions of Electrical Charges Across the Plasma
Membrane; but the bulk of the intracellular and extracellular fluids
are electrically neutral; charge separation exists in a small cloud of
~2 um spread over the intracellular and extracellular surfaces of
the plasma membrane +++++++++++++++
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+++++++++++++++
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+
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+++++++++
- +++++++++
- +++++++++
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--------+++++++++
+++++++
+++++++++
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+++
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++++++++++++++

+
+
+

++++
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Remember this slide from earlier? There is

a differential distributions of different
species of ions (biological charge carriers)
across the plasma membrane.
E.g., giant squid axon (Loligo)
Ion [Cytoplasm] [Extracellular Fluid]
(mM) (mM)
K+ 400 20
Na+ 50 440
Cl- 52 560
Organic- 385 0

And this? Generalizations (although

absolute values differ across species
and among cells from the same
organism)
[K+]I (inside) > [K+]o (outside)
[Na+]I < [Na+]o
[Cl-]I < [Cl-]o
[Organic-]I > [Organic-]o

Building a Model of Membrane Function that

Explains Empirical Measures of Vm and Ionic
Concentration Differences

Exercise #1 = draw equilibrium for a

membrane freely permeable to all
cations, i.e. the laws of simple
diffusion explain the observations.
(See following slide.)
Hint = Vm is 0 mV at time0 and timeeq

Time0
Vm = 0
mV

Na+

K+

Na+

chemical force
magnitude and
direction of net
diffusion
Hypothetical
membrane
freely
permeable
to all cations

insid
e

outside

Timeeq
Vm = 0
mV

K+

K+

Explain:
1) Equal sizes
of ions
2) Doubleheaded
arrows

Na+

Na+

chemical force
magnitude and
direction of net
diffusion
Hypothetical
membrane
freely
permeable
to all cations

3) No Vm

insid
e

outside

Answers:
1) Diffusion continues until both cations are
equally distributed across the membrane (law
of diffusion).
2) The membrane is freely permeable to both
cations so they continue to move across the
membrane once equilibrium is achieved, but
there is no NET exchange of the ions across
the membrane.
3) The original cation concentration gradients
were the same approximate magnitude, so
when ionic concentrations equilibrate across
the membrane the same number of positive
charges have left the cell as have moved into
the cell. Therefore no charge separation, i.e.
Vm, has been created.

What do we do with this model of

membrane function?
Reject it because it does not agree
with empirical measures of Vm and
ionic concentration gradients

Building a Model of Membrane Function that

Explains Empirical Measures of Vm and Ionic
Concentration Differences

Exercise #2 = draw Time0+3xK+ exit for a

membrane permeable only to K+. (See
following slide.)
Hint = Vm is 0 mV at time0

Time0
Vm = 0
mV

Membrane
is
impermeabl
e to ion

K+

Na+

Na+

Cl-

Cl

Organic
insid
e

chemical force
magnitude and
direction of net
diffusion

Organic-

outside

Hypothetical
membrane
freely
permeable
to only K+

Time0+3xK+ exit
Vm =
developing +
K
electrical
force
(and
direction of
movement)
developing

=
K+
+

insid
e

Na+
Cl

Cl-

Organic

chemical force
magnitude and
direction of net
diffusion

Na

Membrane
is
impermeabl
e to ion

Organic-

outside

Hypothetical
membrane
freely
permeable
to only K+

Answers:
1) Diffusion of K+ out of the cell begins at
Time0 and at Time0+3xK+ exit 3 + charges (in the
form of potassium) have left the cell, leaving
net negativity behind inside the cell.
2) The + charges outside the cell repel other +
charges (or the charges inside the cell
attract + charges) causing some K+ to move
back into the cell. This charge separation is
nothing more than a Vm developing across the
plasma membrane.
3) At this point, the chemical force is still
greater than the electrical force and there is
net movement of K+ out of the cell.

Building a Model of Membrane Function that

Explains Empirical Measures of Vm and Ionic
Concentration Differences

Exercise #2 = draw Timeeq for a

membrane permeable only to K+.
Hint = at Timeeq there is no NET
exchange of K+ across the membrane
and
[K+]I > [K+]o

Timeeq

Vm = -75 mV

K+
---

electrical
force =
chemical
force

Membrane
is
impermeabl
e to ion

----Na+

insid
e

+++

Na+

+++

Cl

Cl-

Organic

chemical force
magnitude and
direction of net
diffusion

+++

Organic-

outside

Hypothetical
membrane
freely
permeable
to only K+

Answers:
1) So much K+ has left the cell in response to
its concentration gradient that an electrical
force that is equal in magnitude but opposite
in direction to the chemical force has
developed across the plasma membrane.
2) For every K+ that leaves the cell in response
to the concentration gradient another K+
enters the cell in response to the electrical
force and there is no NET exchange of K+
across the cell.
3) The electrical force is nothing more than
the Vm that develops across the membrane to
balance the concentration gradient.

What do we do with this model of

membrane function?
Accept it because it agrees with
empirical measures of Vm and ionic
concentration gradients.
Thus, the unique permeability
characteristics of the plasma
membrane coupled with the original
K+ concentration gradient leads to
the establishment and
maintenance of the Vm without
expenditure of energy.