Membrane potentials
Xia Qiang, PhD
Department of Physiology
Rm C518, Block C, Research Building, ZJU School of Medicine
Tel: 88208252
Email: xiaqiang@zju.edu.cn
OUTLINE
Resting potential
Graded potential
Action potential
Refractory period
Electrocardiogram
ECG
Electroencephalogram
EEG
Electromyogram
EMG
Extracellular Recording
Intracellular Recording
Opposite charges attract each other and
will move toward each other if not separated
by some barrier.
Only a very thin shell of charge difference
is needed to establish a membrane potential.
Resting membrane potential
A potential difference across
the membranes of inactive
cells, with the inside of the cell
negative relative to the outside
of the cell
Ranging from –10 to –100 mV
Overshoot refers to
the development of
a charge reversal.
A cell is
“polarized”
because
its interior
is more
negative
than its
exterior.
Repolarization is
movement back
toward the
resting potential.
Depolarization
occurs
when ion
movement
reduces the
charge
imbalance.
Hyperpolarization is
the development of
even more negative
charge inside the cell.
•unequal ion distribution
(chemical gradient) across
the membrane
•selective membrane
permeability (cell
membrane is more
permeable to K+)
•Na+-K+ pump
chemical
driving force
----------------++++++++++++++++
electrochemical
balance
electrical
driving force
The Nernst Equation:
RT
[ Ion]o
E
log
ZF
[ Ion]i
R=Gas constant
T=Temperature
Z=Valence
F=Faraday’s constant
K+ equilibrium potential (EK) (37oC)

[ K ]o
Ek  60 log  (mV )
[ K ]i
Begin:
K+ in Compartment 2,
Na+ in Compartment 1;
BUT only K+ can move.
Ion movement:
K+ crosses into
Compartment 1;
Na+ stays in
Compartment 1.
At the potassium
equilibrium potential:
buildup of positive charge
in Compartment 1 produces an electrical potential that
exactly offsets the K+ chemical concentration gradient.
Begin:
K+ in Compartment 2,
Na+ in Compartment 1;
BUT only Na+ can move.
Ion movement:
Na+ crosses into
Compartment 2;
but K+ stays in
Compartment 2.
At the sodium
equilibrium potential:
buildup of positive charge in Compartment 2
produces an electrical potential that exactly
offsets the Na+ chemical concentration gradient.
Difference between EK and directly measured
resting potential
Ek
Observed RP
Mammalian skeletal muscle cell
-95 mV
-90 mV
Frog skeletal muscle cell
-105 mV
-90 mV
Squid giant axon
-96 mV
-70 mV
Goldman-Hodgkin-Katz equation
[ Na  ]o  PNa  [ K  ]o  PK  [Cl  ]i  PCl
Em  60
(mV )



[ Na ]i  PNa  [ K ]i  PK  [Cl ]o  PCl
Role of Na+-K+ pump:
•Electrogenic
•Hyperpolarizing
Establishment of resting
membrane potential:
Na+/K+ pump establishes
concentration gradient
generating a small
negative potential; pump
uses up to 40% of the
ATP produced by that
cell!
Origin of the normal resting membrane
potential
K+ diffusion potential
Na+ diffusion
Na+-K+ pump
Electrotonic Potential
Graded potential
Graded potentials are changes in
membrane potential that are confined to a
relative small region of the plasma
membrane
The size of a
graded potential
(here, graded
depolarizations)
is proportionate
to the intensity
of the stimulus.
Graded potentials can be:
EXCITATORY
or
INHIBITORY
(action potential (action potential
is more likely)
is less likely)
The size of a graded potential is proportional to the size of the stimulus.
Graded potentials decay as they move over distance.
Graded potentials decay as they move over distance.
Graded potentials
(Local response, local
excitation, local potential)
• Not “all-or-none”
• Electrotonic propagation:
spreading with decrement
• Summation: spatial &
temporal
Threshold Potential: level of depolarization needed to trigger
an action potential (most neurons have a threshold at -50 mV)
Excitable cells: a cell in which the membrane
response to depolarisations is nonlinear, causing
amplification and propagation of the
depolarisation (an action potential).
Action potential
Some of the cells (excitable cells) are capable to rapidly reverse their
resting membrane potential from negative resting values to slightly
positive values. This transient and rapid change in membrane potential
is called an action potential
A typical neuron action potential
Negative afterpotential
Spike potential
After-potential
Positive
after-potential
Ionic basis of action potential
(1) Depolarization:
Activation of voltage-gated Na+ channel
Blocker:
Tetrodotoxin (TTX)
(2) Repolarization:
Inactivation of Na+ channel
Activation of K+ channel
Blocker:
Tetraethylammonium
(TEA)
The rapid opening of voltage-gated Na+ channels
explains the rapid-depolarization phase at the
beginning of the action potential.
The slower opening of voltage-gated K+ channels
explains the repolarization and after hyperpolarization
phases that complete the action potential.
An action potential
is an “all-or-none”
sequence of changes
in membrane potential.
Action potentials result
from an all-or-none
sequence of changes
in ion permeability
due to the operation
of voltage-gated
Na+ and K + channels.
The rapid opening of
voltage-gated Na+ channels
allows rapid entry of Na+,
moving membrane potential
closer to the sodium
equilibrium potential (+60 mv)
The slower opening of
voltage-gated K+ channels
allows K+ exit,
moving membrane potential
closer to the potassium
equilibrium potential (-90 mv)
Click here to play the
Voltage Gated Channels
and Action Potential
Flash Animation
Mechanism of the
initiation and
termination of AP
Re-establishing Na+ and K+
gradients after AP
Na+-K+ pump
“Recharging” process
Properties of action potential (AP)
•Depolarization must exceed threshold
value to trigger AP
•AP is all-or-none
•AP propagates without decrement
How to study ?
Voltage Clamp
Nobel Prize in Physiology or
Medicine 1963
"for their discoveries concerning the ionic
mechanisms involved in excitation and
inhibition in the peripheral and central
portions of the nerve cell membrane"
Eccles
Hodgkin
Huxley
Currents recorded under voltage
clamp condition
Patch Clamp
Nobel Prize in Physiology or
Medicine 1991
"for their discoveries concerning the
function of single ion channels in cells"
Erwin Neher
Bert Sakmann
Conduction of action potential
Continuous propagation
in the unmyelinated axon
Click here to play the
Action Potential Propagation
in an Unmyelinated Neuron
Flash Animation
Saltatory propagation in
the myelinated axon
http://www.brainviews.com/abFiles/AniSalt.htm
Saltatorial Conduction: Action potentials jump from one node to the
next as they propagate along a myelinated axon.
Click here to play the
Action Potential Propagation
in Myelinated Neurons
Flash Animation
Excitability: the ability to
generate action potentials
is known as EXCITABILITY
Excitation and Excitability
To initiate excitation (AP)

Excitable cells

Stimulation
 Intensity
 Duration
 dV/dt
Strength-duration Curve
Threshold intensity &
Threshold stimulus
Four action potentials,
each the result of a
stimulus strong enough to
cause depolarization, are
shown in the right half of
the figure.
A refractory period is a period of time
during which an organ or cell is incapable
of repeating a particular action potential
Refractory period following an AP:
1. Absolute Refractory Period: inactivation of Na+ channel
2. Relative Refractory Period: some Na+ channels open
Factors affecting excitability
Resting potential
Threshold
Channel status
The propagation of the action potential from the dendritic
to the axon-terminal end is typically one-way because the
absolute refractory period follows along in the “wake”
of the moving action potential.
SUMMARY
Resting potential:



K+ diffusion potential
Na+ diffusion
Na+ -K+ pump
Graded potential



Not “all-or-none”
Electrotonic propagation
Spatial and temporal summation
Action potential


Depolarization: Activation of voltage-gated
Na+ channel
Repolarization: Inactivation of Na+ channel,
and activation of K+ channel
Refractory period


Absolute refractory period
Relative refractory period
THANK YOU FOR YOUR
ATTENTION!