MEMBRANE POTENTIAL AND ACTION

POTENTIAL

Prof. Dr. Pınar MEGA TİBER

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• Most cells have an electrical potential difference across their plasma
membrane.
• Cytoplasm is negative with respect to extracellular medium.
• The membrane potential results from the unequal distribution of ions in the
intracellular and extracellular fluids.

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• When the intracellular and extracellular concentrations of Na+, K+ and Cl-
ions are examined:
• It is seen that the intracellular K+ concentration is very high compared to the
others.
• On the other hand, Na+ and Cl- ions are more abundant outside the cell.

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• Flow of ions across the membrane is responsible for generating the membrane
potential (rest potential)
These ions flow through “leak channels” down their concentration gradient.

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• A membrane potential is the magnitude of an electrical charge across a
plasma membrane, expressed as the potential inside the cell relative to the
extracellular solution.
• It is measured in millivolts (mV).

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MEMBRANE POTENTIAL

The electrical potential difference

across the resting plasma
membrane is called the resting
potential.
A resting (non-signaling) neuron
has a voltage across its membrane
called the resting membrane
potential, or simply the resting
potential.

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RESTING POTENTIAL

• The resting potential of a cell is defined as the difference in electrical

potential across the plasma membrane when the cell is not stimulated or when
the cell is in a state of relaxation.
• The resting potential is the amount of power that is available to a cell to
maintain its homeostatic state

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IN A CELL, MEMBRANE POTENTIAL IS GENERATED:

• There are large anions inside the cell

• Membrane does not have the same permeability property for Na+ and K+
ions. K+ ions can pass much more easily than Na+ ions.
• There exists a pump on the membrane that transports 3Na+ outward and 2 K+
inward.

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• The resting potential is determined by concentration gradients of ions across
the membrane and by membrane permeability to each type of ion.

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• Creating a membrane potential, requires both ionic concentration gradients
and selective permeability to particular ions.
• An ion’s equilibrium potential is the membrane potential when the membrane
is selectively permeable to that ion only; it can be calculated using the Nernst
equation.
• The membrane potential can be altered by opening and closing different ion
channels.

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• All cells have a membrane potential.
• The resting membrane potential and ability to change the
membrane potential (excitability) varies between different cell
types.
• Membrane potentials provide the basis of cell signaling in all cells.

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ACTION POTENTIAL

• All living systems can create special changes in some characteristic

parameters in response to external stimulus
• Transient changes in the membrane potential of its resting level produce
electrical signals.
• Such changes are the most important way that nerve cells process and transmit
information.

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• These signals occur in two forms:
• graded potentials
• action potentials
• Graded potentials are important in short distances.
• Action potentials are the long-distance signals of nerve and muscle
membranes.

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• Nerve and muscle cells as well as some endocrine, immune, and reproductive
cells have plasma membranes capable of producing action potentials.
• These membranes are called excitable membranes.
• Their ability to generate action potentials is known as excitability.
• All cells are capable of conducting graded potentials, but excitable
membranes can conduct action potentials.

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 CHANGES IN MEMBRANE POTENTIAL
 depolarize
The terms  repolarize are used to describe
 hyperpolarize

the direction of changes in the membrane potential relative

to the resting potential.
Membrane potential (mV)

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Time
The resting membrane potential (at -70 mV) is polarized.
“Polarized” means that the outside and inside of a cell have
a different net charge.
• The membrane is said to be depolarized when its potential
is less negative than the resting level.
• The membrane is repolarized when the potential returns
toward the resting value.
• The membrane is hyperpolarized when the potential is more
negative than the resting level.

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CHANGES IN MEMBRANE POTENTIAL

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 GRADED POTENTIALS
• Short-lived, local changes in membrane potential
• Decrease in intensity with distance
• Their magnitude varies directly with the strength of the stimulus
• Sufficiently strong graded potentials can initiate action potentials

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GRADED POTENTIALS

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GRADED POTENTIALS
• Can only travel short distances
• Voltage changes in graded potentials are gradual
• Current quickly spreads and disappears due to the leaky plasma membrane

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TERMS DESCRIBING THE MEMBRANE POTENTIAL

Potential = potential The voltage difference between two

difference points.
Membrane potential The voltage difference between the
=transmembrane potential inside and outside of a cell.

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TERMS DESCRIBING THE MEMBRANE POTENTIAL
Resting membrane potential The steady transmembrane potential
= resting potential of a cell that is not producing an
electric signal.
Action potential A brief all-or-none depolarization of
the membrane, reversing polarity in
neurons; it has a threshold and
refractory period and is conducted
without decrement.
Threshold potential The membrane potential at which an
action potential is initiated.

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 CHANGING THE MEMBRANE POTENTIAL
• The membrane potential can be changed by altering the membrane’s permeability
to different ions – i.e. opening and closing ion channels.
• If the membrane becomes more permeable to an ion, it will cause the membrane
potential to shift towards the equilibrium potential for that ion.
• The value of the membrane potential can change in two directions:
• Depolarisation – The membrane potential becomes less negative
• Hyperpolarisation – The membrane potential becomes more negative
• Opening Na+ or Ca2+ channels will result in depolarisation, whereas opening K+ or
Cl- channels will result in hyperpolarisation.
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 • Depending upon the initiating event, graded potentials can occur
in either a depolarizing or a hyperpolarizing direction.
Membrane potential (mV)

Such experiments show that graded potentials

(a) can be depolarizing or hyperpolarizing,
(b) can vary in size.
* The resting membrane potential is -70 mV.
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• Charge is lost across the membrane because the
membrane is permeable to ions through open
membrane channels.
• As a result, the membrane potential changes decreases
by the distance from the initial site.

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• Because the electrical signal decreases with distance, graded
potentials can function as signals only over very short
distances.
• If additional stimuli occur before the graded potential has
died away, these can be added to the depolarization from
the first stimulus. This process is termed summation.
• Graded potentials are the only means of communication
used by some neurons.
• They play very important roles in the initiation and
integration of long-distance signals by neurons and some
other cells. 28
• The mechanisms by which a neuron sorts out its various graded
potentials and decides whether to generate an action potential
is called integration.
• many factors affect integration, including signal strength, time
course, type of transmission, spike frequency adaptation,
accommodation, and threshold.

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ACTION POTENTIAL
• Neurons communicate over long distances by generating and
sending an electrical signal called a nerve impulse, or action
potential.

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outside

ATP

inside

• When a stimulus applied to the membrane in

a resting potential, what happens???

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DISTURBED BY THE
STIMULUS

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ACTION POTENTIALS (APS)

• A brief reversal of membrane potential with a total amplitude of 100 mV

• Action potentials are only generated by muscle cells and neurons
• They do not decrease in strength over distance
• They are the principal means of neuronal conduction
• An action potential in the axon of a neuron is a nerve impulse

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• is very rapid
• All-or-None Law: In any single nerve
or muscle fiber the response to a
stimulus above threshold level is
maximal and independent of the
intensity of the stimulus.

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• some cells have plasma membranes capable of producing
action potentials.
• Voltage-dependent ion channels in the membrane are the
basis for APs.
• The propagation of action potentials is the mechanism used
by the nervous system to communicate over long distances.

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 RESTING STATE
• Na+ and K+ channels are
closed
• Leakage accounts for small
movements of Na+ and K+
• Each Na+ channel has two
voltage-regulated gates
• Activation gates –
closed in the resting
state
• Inactivation gates –
open in the resting
state

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 DEPOLARIZATION PHASE
• Na+ permeability increases; membrane potential
reverses
• Voltage gated Na+ channels are opened, but K+ are
closed
• Threshold – a critical level of depolarization
(-55 to -50 mV)
• At threshold,
depolarization
becomes
self-generating
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 REPOLARIZATION PHASE
• Sodium inactivation gates close
• Membrane permeability to Na+ declines to resting levels
• As sodium gates close, voltage-sensitive K+ gates open
• K+ exits the cell and
internal negativity
of the resting neuron
is restored

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 HYPERPOLARIZATION
• Potassium gates remain open, causing an excessive efflux of K+
• This efflux causes hyperpolarization of the membrane (undershoot)
• The neuron is
insensitive to
stimulus and
depolarization
during this time

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ACTION POTENTIAL:
ROLE OF THE NA-K PUMP
• Repolarization
• Restores the resting electrical conditions of the neuron
• Does not restore the resting ionic conditions
• Ionic redistribution back to resting conditions is restored by the
sodium-potassium pump

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 THE ACTION POTENTIAL: AN OVERVIEW

• The action potential is a large change in membrane potential from

a resting value of about -70 mV to a peak of about +30 mV, and
back to -70 mV again.
• The action potential results from a rapid change in the
permeability of the neuronal membrane to Na+ and K +. The
permeability changes as voltage-gated ion channels open and
close.

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 Action potentials are rapid,
large alterations in the
membrane potential during
which time the membrane
potential may change 100
mV, from -70 to 30 mV, and
then repolarize to its resting
membrane potential .

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WHAT IS RESPONSIBLE FOR THE CHANGE IN MEMBRANE
PERMEABILITY DURING THE ACTION POTENTIAL?
• Although called “action”potential, it is NOT an active
(energy-consuming) event for the cell.
• It is purely a passive event. It is due to diffusion of ions!
• It is dependent on
• ionic electrochemical gradients (Na+, K+) and
• the membrane’s permeability.
Excitable cells have “fickle(unstable)” cell membranes…they
keep changing their permeabilities.
What determines the membrane’s permeability at any
moment?
Answer: GATED ion channels—These allow SIMPLE
DIFFUSION of ions down their electrochemical gradients
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 IONIC BASIS OF THE ACTION POTENTIAL

• The action potential is initiated by a transient change in

membrane ion permeability, which allows Na+ and K + ions to
move down their concentration gradients.

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Ionic Basis of the Action Potential

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 Ionic Basis of the Action Potential

When a stimulus applied in the membrane of the cell

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 Ionic Basis of the Action Potential
Voltage gated Na + channels are open immediately,
and K + channels open slowly

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 Ionic Basis of the Action Potential
Voltage gated Na+ channels close

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Ionic Basis of the Action Potential

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CHANNELS OF APS

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 1. PHASE: In the resting state,
• The leak channels in the plasma membrane
are predominantly those that are
permeable to K+ions.
• Very few Na+ ion
channels are open.
• The resting potential is
close to the K+
equilibrium potential.

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• The action potential begins with
depolarization of the membrane in
response to a stimulus.
• This initial depolarization opens
sodium channels, which increases the
membrane permeability to sodium
ions

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  Phase 2

• More sodium ions move into the cell.

• The cell becomes more and more
depolarized until a threshold (2) is
reached to trigger the action
potential. This is called the threshold
potential.

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 THRESHOLD & ACTION POTENTIALS &
REFRACTORY PERIOD
• Threshold – membrane is depolarized by 15 to 20 mV
• Established by the total amount of current flowing through the membrane
• Weak (subthreshold) stimuli are not relayed into action potentials
• Strong (threshold) stimuli are relayed into action potentials
• All-or-none phenomenon – action potentials either happen completely, or not at all
• Refractory period is a period of time is the amount of time it takes for an
excitable membrane to be ready for a second stimulus once it returns to its
resting state following an excitation.
• It most commonly refers to electrically excitable muscle cells or neurons.
Absolute refractory period corresponds to depolarization and repolarization,
whereas relative refractory period corresponds to hyperpolarization.
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  Phase 3

• After the threshold potential is

reached, voltage-gated sodium
channels open (3).
• The membrane potential overshoots,
becoming positive on the inside and
negative on the outside of the
membrane.
• In this phase, the membrane
potential approaches but does not
quite reach the sodium equilibrium
potential (ENa=60 mV). 58
  Phase 4

• At the peak of the action

potential (4), Na+ permeability
abruptly decreases and voltage-
gated potassium channels open.

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  Phase 5

• The membrane potential begins

to rapidly repolarize (5) to its
resting level.

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  Phase 6

•After the sodium channels

have closed, some of the
voltage-gated potassium
channels are still open, and in
nerve cells there is generally
a small hyperpolarization (6)
of the membrane potential
beyond the resting level
called the after
hyperpolarization.
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  Phase 7
• Once the voltage-gated
potassium channels close, the
resting membrane potential is
restored (7).
•Na+/ K+ pump restore
potential to -70mV in 1-2 msec.

• Chloride permeability does not

change during the action
potential.
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• 0: Between -70 to -40 mV Na+
channels open & Na + ions flood
inside.
• 1: At -40mV, Voltage-gated Na+
50mV
channels open & Na + ions flood
inside.
• 2: At +50mV, Na + channels 0

close & K + channels open so that

K + ions flood outside. -50mV

• 3: Voltage decreases to -90 mV

& K + channels close -100mV

• 4: Na + /K + pump restores
potential to -70mV in 1-2msec. 63
Resting membrane Potential
Na+ concentrated on outside.
K+ concentrated on inside
Depolarization Begins
Na+ gates open and Na+ begins to flow rapidly into the axon

Depolarization Continues
Na+ continues to flow rapidly into the axon
K+ gates open and K+ begins to flow slowly out of the axon

Depolarization Peaks
Na+ channels close and Na+ stops flowing into the axon
K+ has only just started to leave the axon
Na+ and K+ are now both briefly concentrated on the inside of the
axon resulting in the inside being positive relative the outside of the
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axon
Hyperpolarization Begins
The Na+ channels close, the Na+ pump forces the Na+ out of the
axon, back to where it started.
K+ channels start to close. Because positive ions are both
concentrated on the outside of the axon, the outside is now more
positive than when the axon is at rest. In other words, the inside is
more negative than resting.
Axon Returns to The Resting State
Na+ has been pumped back outside
K+ has been pump back inside

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• Many cells that have graded potentials cannot form action
potentials because they have no voltage-gated sodium channels.

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WHAT IS ACHIEVED BY LETTING NA + MOVE INTO
THE NEURON AND THEN PUMPING IT BACK OUT?

• Na+ movement down its electrochemical gradient into

the cell generates the electrical signal necessary for
communication between the parts of the cell.
• Pumping Na+ back out maintains the concentration
gradient so that, in response to a new stimulus, Na+ will
again enter the cell and create another signal.
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CHARACTERISTICS OF ACTION POTENTIAL

• 1- It propagates along the axon with the same size

(amount of depolarization) and shape (change of
potential with time)
• 2- It is an all or none response. It starts only if a
threshold point is passed. The ion channels are either
open or closed; there is no half-way position. And this
means that the action potential always reaches +40mV
as it moves along an axon, and it is never reduced by
long axons.
• 3- Size and shape differ from one type of cell to
another.
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Different types of action potential

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ABSOLUTE REFRACTORY PERIOD

• Time from the opening of the Na+ activation gates until the closing of
inactivation gates
• The absolute refractory period:
• Prevents the neuron from generating an action potential
• Ensures that each action potential is separate
• Enforces one-way transmission of nerve impulses

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PROPAGATION OF AN ACTION POTENTIAL (TIME =
0MS)

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PROPAGATION OF AN ACTION POTENTIAL (TIME =
1MS)
• Ions of the extracellular fluid move toward the area of greatest negative
charge
• A current is created that depolarizes the adjacent membrane in a forward
direction
• The impulse propagates away from its point of origin

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PROPAGATION OF AN ACTION POTENTIAL (TIME =
1MS)

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PROPAGATION OF AN ACTION POTENTIAL (TIME =
2MS)
• The action potential moves away from the stimulus
• Where sodium gates are closing, potassium gates are open and create a
current flow

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PROPAGATION OF AN ACTION POTENTIAL (TIME =
2MS)

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CODING FOR STIMULUS INTENSITY

• All action potentials are alike and are independent of stimulus intensity
• Strong stimuli can generate an action potential more often than weaker stimuli
• The central nervous system determines stimulus intensity by the frequency of
impulse transmission

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CODİNG FOR STİMULUS INTENSİTY

• Upward arrows – stimulus applied

• Downward arrows – stimulus stopped

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CODİNG FOR STİMULUS INTENSİTY

• Length of arrows – strength of stimulus

• Action potentials – vertical lines

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 CONDUCTION VELOCITIES OF AXONS
• Conduction velocities vary widely among neurons
• Rate of impulse propagation is determined by:
• Axon diameter – the larger the diameter, the faster the impulse
• Presence of a myelin sheath – myelination dramatically increases impulse
speed

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SALTATORY CONDUCTION

• Current passes through a myelinated axon only at the nodes of Ranvier

• Voltage-gated Na+ channels are concentrated at these nodes
• Action potentials are triggered only at the nodes and jump from one node to
the next
• Much faster than conduction along unmyelinated axons

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SALTATORY CONDUCTION

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References
• Biyofizik, Ferit Pehlivan
• Physics for the Health Sciences C.Nave and B. Nave
• Physics for the Life Sciences A.H.Cromer
• Physics, Health and the Human Body Gustafson
• Human Physiology Schmidt and Thews
• The Ciba Collection Atlas Nettler