NERVE PHYSIOLOGY

MEMBRANE
POTENTIAL
Transduction of signals at the cellular level
Resting Membrane Potential
Action Potential
Why do we need to know about
RMP and AP?
 Transduction of signals at the
cellular level

Initial
segment AP

Neurotransmitter

Neurotransmitter
releasing
 Nerve Impulse Transmission Within A
Neuron
 For the nervous system to function, neurons must be able to
send and receive signals.
 These signals are possible because each neuron has a
charged cellular membrane (a voltage difference between the
inside and the outside).
 The charge of this membrane can change in response to
neurotransmitter molecules released from other neurons and
environmental stimuli.
 Any voltage is a difference in electric potential between
two points; for example, the separation of positive and
negative electric charges on opposite sides of a resistive
barrier.
 To understand how neurons communicate, one must first
understand the basis of charged membranes and the
baseline or ‘resting' membrane charge.
 Preliminary knowledge

What is necessary to know beforehand

 Cell membrane
Phospholipid bilayer

Proteins peripheral
integral non penetrating
penetrating (transmembrane)
Cell Membrane

Copyright © Allyn & Bacon 2004

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!
That’s 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
 This separation of charges generates an electric
field or potential difference across the
membrane, given by V = Q/C or
charge/capacitance.
 Typical membrane has a capacitance of 1
μF/cm2, about 70% of which is due to the lipid
bilayer and the rest because of embedded
proteins.
 The lipid bilayer membrane that surrounds a neuron is
impermeable to charged molecules or ions.
 To enter or exit the neuron, ions must pass through special
proteins called ion channels that span the membrane.
 Ion channels have different configurations: open, closed,
and inactive .
 Some ion channels need to be activated in order to open
and allow ions to pass into or out of the cell.
 These ion channels are sensitive to the environment and
can change their shape accordingly.
 Ion channels that change their structure in
response to voltage changes are called voltage-
gated ion channels.
 Voltage-gated ion channels regulate the relative
concentrations of different ions inside and outside
the cell.
 The difference in total charge between the inside
and outside of the cell is called the membrane
potential
http://sites.sinauer.com/neuroscience5e/animations02.01.html
Ion channels in the cell membrane
 Resting channels - normally open

 Gated channels - closed when the membrane is at rest opening is

regulated by
» 1. Membrane potential (voltage gated)

» 2. (chemicaly gated)

» 3. Membrane potential plus ligand binding (Voltage and

chemicaly gated)
» 4. Membrane stretch (mechanicaly gated)
ION CHANNEL CONFIGURATIONS
 Voltage-gated ion channels are closed at the resting
potential
 Open in response to changes in membrane voltage.
 After activation, they become inactivated for a brief
period and will no longer open in response to a
signal.
http://sites.sinauer.com/neuroscience5e/animations02.01.html
 Membrane Potential
 Membrane potential also called as transmembrane
potential or membrane voltage
 Differences in the concentrations of ions on opposite
sides of a cellular membrane lead to a voltage called
the membrane potential. 
 Cells usually have a negative membrane potential and
that there is an unequal distribution of ions across the
membrane.
 With respect to the exterior of the cell, typical values of
membrane potential range from –40 mV to –80 mV.
 K+ outside the cell < K+ inside the cell
 Diffusion is trying to drive potassium out of the cell (from
high to low).
 Potassium does not usually undergo any net movement as
the electrical force (negative on the inside and remember
that negative charges attract positive ones such as
potassium ions) is trying to drag the potassium inward
(toward the negative).
 As long as these two forces push potassium in opposite
directions and push with equal force, there will be no net
movement of potassium even though it is freely
permeable.
 Under these conditions, potassium is said to be
in equilibrium.
Resting Membrane Potential
 For inactive cells, the relatively-static membrane potential is
known as the resting membrane potential.
 The resting potential would be maintained if there were
no action potentials, synaptic potentials, or other active
changes in the membrane potential.
 It is dominated by the potassium ions in the system that has
the greatest conductance across the membrane.
 A neuron at rest is negatively charged inside of a cell and it
is approximately −70 mV
 This number varies by neuron type and by species.
 This voltage -70mV is called the resting membrane
potential and is caused by differences in the
concentrations of ions inside and outside the cell.
 If the membrane were equally permeable to all ions, each
type of ion would flow across the membrane and the
system would reach equilibrium.
 ions cannot simply cross the membrane and the
concentrations of several ions are different inside and
outside the cell.
 The difference in the number of positively-charged
potassium ions (K+) inside and outside the cell dominates
the resting membrane potential.
 When the membrane is at rest, K+ ions accumulate inside
the cell
 The negative charge within the cell is created by the cell
membrane being more permeable to K+ movement than
Na+ movement.

•The (a) resting membrane potential is a result of different

concentrations of Na+ and K+ ions inside and outside the
cell.
 In neurons, potassium ions (K+) are maintained at high
concentrations within the cell, while sodium ions (Na+)
are maintained at high concentrations outside of the cell.
 The cell possesses potassium and sodium leakage
channels that allow the two cations to diffuse down their
concentration gradient.
 However, the neurons have far more potassium leakage
channels than sodium leakage channels.
 Therefore, potassium diffuses out of the cell at a much
faster rate than sodium leaks in.
 More cations leaving the cell than entering it causes the
interior of the cell to be negatively charged relative to
the outside of the cell.
 The actions of the sodium-potassium pump help to
maintain the resting potential, once it is established.
 Sodium-potassium pumps bring two K+ ions into the cell
while removing three Na+ ions per ATP consumed.
 As more cations are expelled from the cell than are taken
in, the inside of the cell remains negatively charged
relative to the extracellular fluid.
Na+- K+ pump
Na+- K+ pump
Extrude 3 Na+ ions
Bring in 2 K+ ions

Unequal distribution of ions

Na+ extracelullary
K+ intracelullary
 INTRACELLULAR RECORDINGS FROM
NEURONS
 The potential difference across a nerve cell membrane can
be measured with a microelectrode whose tip is so small
that it can penetrate the cell without producing any
damage.
 When the electrode is in the bath (extracellular medium)
there is no potential recorded because the bath is
isopotential.
 If the microelectrode is carefully inserted into the cell,
there is a sharp change in potential.
 The reading of the voltmeter instantaneously changes
from 0 mV, to reading a potential difference of -60 mV
inside the cell with respect to the outside.
 The potential that is recorded when a living cell is
impaled with a microelectrode is called the resting
potential, and varies from cell to cell.
 Here it is shown to be -60 mV, but can range between
-80 mV and -40 mV, depending on the particular type of
nerve cell.
 In the absence of any stimulation, the resting potential is
generally constant.
 Resting membrane potential
 the unequal distribution of ions on the both sides of the
cell membrane;
 the voltage difference of quiescent cells;
 the membrane potential that would be maintained if there
weren’t any stimuli or conducting impulses across it;
 determined by the concentrations of ions on both sides of
the membrane;
 a negative value, which means that there is an excess of
negative charge inside of the cell, compared to the
outside.
 much depended on intracellular potassium level as the
membrane permeability to potassium is about 100 times
higher than that to sodium.
The Nernst Equation
 a mathematical equation applied in physiology, to
calculate equilibrium potentials for certain ions.


R = Gas Constant

T = Absolute temperature (K)

E = The potential difference across the membrane

F = Faradays Constant (96,500 coulombs/mole)

z = Valency of ion
The Goldman-Hodgkin-Katz Equation
 Is a mathematical equation applied in Physiology, to
determine the potential across a cell's membrane, taking
in account all the ions that are permeable through it.

 E = The potential difference across the membrane

 P = Permeability of the membrane to sodium or
potassium
 [ ] = Concentration of sodium or potassium inside or
outside
Resting membrane potential
 MEMBRANE POTENTIALS

Excitatory Action threshold

Resting Inhibitory
Post-synaptic Potential
Potential Post-synapt
potential
potential
Resting membrane potential varies according to types
of cells
For example:
Smooth muscle cells: −50 mV
Astrocytes: −80/−90 mV
Neurons: −70 mV
voltage gated
sodium channel
Resting and Action Potentials
 ACTION POTENTIALS
 Electrodes were placed on the
surface of an optic nerve
 Then 1-sec duration flashes of light
of varied intensities were presented
to the eye;
 First dim light, then brighter lights.
 Dim lights - no changes in the
activity,
 Brighter lights produced small
repetitive spike-like events called
action potentials, nerve impulses, or
sometimes simply spikes.

Action potentials are the basic events the nerve cells use to transmit
information from one place to another.
 ACTION POTENTIALS
 Only neurons and muscles have action potentials (not all
neurons).
 Due to voltage-gated Na+ channels.
 Most in axons, at initial segment (axon hillock) and
nodes of Ranvier. A few in big dendrites where
depolarizations need a boost.
 Channel ionic currents are studied by voltage clamps
and patch clamps.
 ACTION POTENTIAL
 When the cell membranes are
stimulated, there is a change in
the permeability of the
membrane to sodium ions (Na+).
 The membrane becomes more
permeable to Na+ and K+,
therefore

 Na+ ions diffuse into the cell down a concentration

gradient.
 The entry of Na+ disturbs the resting potential and causes
the inside of the cell to become more +ve than outside.
 DEPOLARISATION
In order for the neuron to  As the inside of the cell has
generate an action potential become more positive than
the membrane potential must the inside of the cell, the
reach the threshold of membrane is now
excitation. DEPOLARISED.
 When enough sodium ions
enter the cell to depolarise the
membrane to a critical level
(threshold level) an action
potential arises which
generates an impulse.
 ALL-OR-NONE PRINCIPLE
 Throughout depolarisation, the Na+ continues to rush
inside until the action potential reaches its peak and the
sodium gates close.
 If the depolarisation is not great enough to reach threshold,
then an action potential and hence an impulse are not
produced.
 Ie. The action potential fails to occur if the stimulus is
subthreshold in magnitude
 This is called the All-or-None Principle.
 FEATURES OF ACTION POTENTIAL
 3 important features
 1st - The nerve action potential has a short duration (about
1 msec). 
 2nd - Nerve action potentials are elicited in an all-or-
nothing fashion. 
 3rd - Nerve cells code the intensity of information by the
frequency of action potentials.
 When the intensity of the stimulus is increased, the size of
the action potential does not become larger. Rather, the
frequency or the number of action potentials increases.
 In general, the greater the intensity of a stimulus, the
greater the number of action potentials elicited.
 Similarly, for the motor system, the greater the number of
action potentials in a motor neuron, the greater the intensity
of the contraction of a muscle that is innervated by that
motor neuron. 
 Action potentials are of great importance to the functioning
of the brain since they propagate information in the nervous
system to the central nervous system and propagate
commands initiated in the central nervous system to the
periphery.
 Na+ channels open in APabsolute refractory period.

o voltage-gated K+ channels in mammalian unmyelinated axons)

Steps to Action
Potential
 Step 1: Threshold is Reached
 An impulse is triggered in the neuron’s dendrite
when stimulated by:

Pressure

Heat

Light

NT - chemical messenger from another neuron
(synaptic transmission)
 Minimal level of stimulation that causes the axon
to fire is called Stimulus Threshold
 Step 2: Action Potential Begins
 When neuron fires, its axon membrane is
selectively permeable.
 Gates in the axon called ion channels open allowing
positive sodium ions to enter the axon while
potassium ions leave causing a brief positive
electrical charge in the axon (depolarized).
 The brief positive charge is action potential.
 Depolarization Ahead of AP

 AP opens cell membrane to allow sodium (Na+) in

 Inside of cell rapidly becomes more positive than outside
 This depolarization travels down the axon
 Step 3: Refractory Period
• As the next gates open allowing positive sodium ions in,
the previous gates close and begin to pump the positively
charged sodium ions out of the axon
 This step is called the refractory period and the axon
cannot fire again until it returns to resting potential
(negative polarized state).
 Repolarization follows

 After depolarization potassium (K+) moves out restoring

the inside to a negative voltage
 This is called repolarization
 The rapid depolarization and repolarization produce a
pattern called a spike discharge
 Finally, Hyperpolarization

 Repolarization leads to a voltage below the resting potential,

called hyperpolarization
 Now neuron cannot produce a new action potential
 It must return a resting state
1. Threshold is reached
2. +Na ions enter beginning
of axon
3. This triggers the next Na
gates to open.
4. As they open & allow in
Na+,
5. Previous gates begin
pumping the Na+ out.
6. Before the action
potential has reached the
end, the beginning of the
axon is back at resting
potential & ready for
another firing.
 CHARACTERISTICS OF ACTION
POTENTIALS

Requires specific voltage- gated ion channels

AP are the result of rapid changes in ion conductance

AP occur only on regions of cell membranes that are electrically
excitable and is propagated down the axon membrane

AP generally are a standard size and shape for a specific cell type; It
has a fixed amplitude

All or none - when membrane reaches threshold an AP is generated
(Not-Graded)

Time - AP not only have a specific size and shape but also exists
within a specific time frame, ave. 1 to 5 msec
IMPORTANCE OF ACTION POTENTIALS

 Nerve traffic, muscle contraction, hormone release, G.I.

secretions, Cognitive thought, etc.
 Action Potentials are required for the senses - Sight,
hearing, and touch are all dependent on action potentials
for transmission of information to the brain
 Threshold stimuli (Graded Potential) cause the
generation of an action potential
 POTENTIAL


1. Threshold - Membrane potential at which voltage gated
channels will open

2. Rising phase - as Na+ channels open membrane
potential begins to shift toward the equilibrium potential
for Na+ (Nernst Potential for Na+)

3. Overshoot - The point at which the membrane potential
becomes positive. The greater the overshoot potential the
further the membrane will stay above threshold

4. Peak - At the peak of the action potential the sodium
conductance begins to fall (Closure of the slow gate)

5. Repolarization - Inactivation of sodium channels and
opening of the K+ channels (Opening of the K+ voltage
channel slow gate) causes repolarization

6. Threshold - As the membrane potential passes back
through threshold the voltage gated channels reset (both
the Na+ and K+ channels)
Action Potential Generation
 Action Potential Generation
Properties
 Refractory periods are
times when it is either
impossible or more
difficult than normal to
generate a second
action potential.
 Action Potential Generation
Properties
Absolute Refractory
 During this period the
voltage gated channels
responsible for the action
potential have not reset
and therefore, do not
respond to stimulation.
 Action Potential Generation
Properties

Relative Refractory
 This period corresponds
to the positive after
potential period and due
to the hyperpolarization
of the cell it is more
difficult to generate a
second action potential.
 Latent period
 After a stimulus is applied to a nerve, there is a
latent period before the start of the action
potential.
 This interval corresponds to the time it takes the
impulse to travel along the axon from the site of
stimulation to the recording electrodes.
 Its duration is proportionate to the distance
between the stimulating and recording electrodes
and inversely proportionate to the speed of
conduction.
 Smooth muscles

• Sensitive to stretch
• Slow wave potential
• Spike potential