Membrane Potential

Dr. R. Periasamy
Dept of Health science
Aksum University
 Basic Organization
sensory receptor (sensory input)  integration  (motor output)  effector

• Sensory Input triggered by

stimuli.
– conduction of signals to
processing center.

• Integration
– interpretation of sensory signals
within processing centers.

• Motor output
– conduction of signals to effector
cells (i.e. muscles, gland cells)
Human cell
 Distribution of ions
• In ICF, the concentration of
K+ is high.
– It is balanced by a high
concentration of negatively
charged proteins and other
anions (phosophates).
• In ECF, the concentration
of Na+ is high.
– It is balanced by a high
concentration of Cl- ions.
 Resting membrane potential
• Resting membrane potential (RMP) exists due to small buildup of negative
ions in cytosol and an equal buildup of positive ions in ECF on outside
surface of membrane.

• Such a separation of positive and negative electrical charges is a form of

potential energy,
• which is measured in volts or millivolts (mV).

– The greater the difference in charge across the membrane, the larger the membrane
potential.
• In neurons, the RMP ranges from - 40 to - 90 mV.
• A typical value is - 70 mV.
• In body cells, RMP varies from - 5 mV to - 100 mV in different types of cells.
 Resting membrane potential
• 1. Unequal distribution
of ions in ECF and
Indifferent electrode
cytosol.

• 2. Inability of most
anions to leave the
cell.

• 3. Electrogenic nature
of the Na+/K+ ATPase.
 Unequal Distribution of Ions
• ECF rich in Na+ ions and chloride ions (Cl-).
• In cytosol, the main cation is K+ and two dominant anions are
phosphates attached to ATP and amino acids in proteins.

– Plasma membrane has more K+ leakage channels than Na+ leakage

channels.
– The number of K+ that diffuse down their concentration gradient out of
cell into ECF is greater than number of Na+ that diffuse down their
concentration gradient from the ECF into the cell.

• As more and more positive K+ exit, inside of the membrane

becomes increasingly negative and outside of the membrane
becomes increasingly positive.
Resting Membrane Potential
Concentration gradient of ions
 Role of protein in RMP
• Due to concentration gradient and more leaky channels.
– Diffusion of K+ to outside the cell is more than diffusion of Na+
to inside the cell.

• Cells are impermeable to negatively charged proteins and

other large anions (phosphates bind with ATP) found
inside, due to large size.
– The concentration gradient acts as a chemical force that
pushes K+ out of the cell.
 Electrogenic nature of Na+/K+ ATPases
– Membrane permeability to Na+ is very low because there are only a few Na+ leakage
channels.
– But cell has more potassium leak channels.

• The Na/K ATPase,

– which pump 3Na+ to outside and 2K+ to inside the cell.
– This pump remove more positive charges to outside the cell and creates negative charge
inside the cell.
• They are electrogenic. They contribute to negativity of RMP.

• Their total contribution is very small, only -3 mV of the total -70 mV RMP in a
typical neuron.
 Role of K and Cl ions in RMP
+ -

• Two forces act on K+.

– Together these forces are called Electrochemical Gradient.
• 1. The Concentration Gradient or Chemical Force
– Causes K+ to diffuse out of the cell.
• 2. The Electrical potential or Electrical force
– Pulls K+ into the cell

• Since the chemical and electrical forces on K+ are equal and opposite,
there will be no net movement of K+ across the membrane.
• Moreover diffusion of Cl- inside the cell creates more negative charge
inside cell.
 Graded Potentials
• A stimulus is any change in environment that is strong
enough to initiate an action potential.

• Graded potential (GP) is a small deviation from the MP that

makes the membrane either more polarized or less polarized.

– Membrane more polarized (inside more negative) it is termed a

hyperpolarizing graded potential.
– Membrane less polarized (inside less negative), it is termed a
depolarizing graded potential.
Graded Potential
 Graded potential (GP)
• A graded potential occurs when a stimulus causes
mechanically gated or ligand-gated ion channels to
open in an excitable cell’s plasma membrane.

– GP occur mainly in dendrites and cell body of neuron.

– Electrical signals are graded based on amplitude (size),
depending on the strength of stimulus.
– GP are useful for short-distance communication only.
• They called as decremental conduction.
Structure of Neuron
1. Dendrites

2. A cell body

3. An axon
Graded potential to open the gates
 Summation of Graded Potential
• Individual GP may be decremented
conduction.
• GP become stronger and last longer
by summating with other GP.
• If two depolarizing GP are added,
the net result is a larger
depolarizing GP.
• GP that occur in sensory receptors
and sensory neurons are called
generator potentials.
• GP occurs in dendrites or cell body
of a neuron in response to a
neurotransmitter, called
postsynaptic potential.
 Action Potential (AP)
• Rapid changes in Membrane potential (MP).
• Sudden change from normal resting negative membrane
potential to a positive potential and back to negative potential.

• An electrical signal that propagates along the surface of the

membrane of a neuron.

– AP moves along nerve fiber until it comes to axon’s end.

– Successive changes in MP over a time in milliseconds (msec).
– At rest neurons are more permeable to K+ than Na+ .
 Threshold potential
• An AP occurs in membrane of a neuron when
depolarization reaches threshold potential.
• For particular neuron threshold potential is
constant.
– An AP will not occur in response to a sub-threshold
stimulus.
– This characteristic of an AP is known as the all-or-none
principle.
 Action potential
• Resting stage
– Membrane is said to be “polarized” –70 mV negative MP inside the cell.
• Depolarization phase.
– The negative MP becomes less negative, reaches zero and then becomes
positive +30 mV.
– The rapid depolarization duet to inward Na+ current.
• Repolarization phase.
– The MP is restored to resting state of – 70 mV.
– Is caused by an outward K+ current.
• Hyperpolarizing phase
– MP temporarily becomes more negative than the resting level (– 90mV).
 Voltage gated ion channels
• Voltage gated Na+ channels
– Allow Na+ ions to enter into the nerve fiber .
– Activation gate. (closed during resting state)
– Inactivation gate .
• (Closed during Action potential and Excess K+ in ECF).
– Tetrodotoxin and lidocine block these voltage gated Na+ channels and
abolish AP.
• Voltage gated K+ channels
– Allow K+ ions to move out of nerve fiber.
• Voltage gated Ca2+ channels (end of the axon)
– Allow Ca2+ ions to enter inside the nerve fiber.
Action Potential
Overview of Neural Impulse
Channel during action potential
Millions of Na+

20,000 Na

-70 mV -70 to +30 mV +30 to -70 mV

-70 mV +30 to -70 mV

 Refractory Period
• Absolute Refractory Period.
• The time after an AP begins in nerve fiber cannot generate
another AP in response to threshold stimulus.
– Inactivated Na+ channels are closed.

• Relative refractory period

• Period of time during which a second AP can be initiated, but
only by a larger than normal stimulus.
– Voltage-gated K+ channels are still open after inactivated Na
channels have returned to their resting state.
 Propagation of Action Potentials
• AP in a neuron must travel from trigger zone of axon
to the axon terminals.
– Transmission of AP along nerve fiber called propogation.
• AP regenerates over and over at adjacent regions of
membrane from trigger zone to axon terminals.
• There are two types of propagation:
– 1. Continuous conduction.
– 2. Saltatory conduction.
Propagation of action potential
 Continues Conduction
• Step by- step depolarization
and repolarization of each
adjacent segment of the
plasma membrane.

• The AP propagates only a

relatively short distance in a
few milliseconds.

• Continuous conduction
occurs in unmyelinated
axons and in muscle fibers.
 Saltatory conduction
• AP in myelinated axons.
• Myelin sheath act as an insulator around axons and
increase conduction velocity.
• Nerve impulse stimulate Na+ and K+ channels only at
nodes of ranvier. Where myelin sheath absent.
– AP at the first node generates the depolarization
potential which opens second node.
Saltatory conduction
Propagation of action potential
 Factors That Affect the Speed
of Propagation
• 1. Amount of myelination.
– AP propagate more rapidly along myelinated axons than
unmyelinated axons.
• 2. Axon diameter.
– AP Propagate faster in Larger-diameter axons than
smaller ones, due to their larger surface areas.
• 3. Temperature.
– Axons propagate AP at lower speeds when cooled.
 Comparison of neurons

Property A fiber B fiber C fiber

Axon diameter µm 5–20 2–3 0.5–1.5
Brief absolute Longer absolute Longest absolute
Refractory period
refractory period refractory period refractory periods
Nerve impulse 12 to 130 m/sec 15 m/sec 0.5 to 2 m/sec
propagation
 TRANSMISSION OF NERVE IMPULSE
AT SYNAPSES
• The neuron sending the signal is presynaptic neuron.
• The neuron receiving the message is postsynaptic neuron.
• Most synapses are either
– axodendritic (from axon to dendrite),
– axosomatic (from axon to cell body),
– axoaxonic (from axon to axon).
• The two types of synapses— electrical and
chemical —differ both structurally and functionally.
 Electrical synapses
• AP impulses conduct directly between adjacent cells
through structures called gap junctions.
– Each gap junction contains a hundred of tubular
connexons, which act like tunnels to connect cytosol of
the two cells directly.
• As ions flow from one cell to next through
connexons, the AP spreads from cell to cell.
– Gap junctions are common in visceral smooth muscle
and cardiac muscle.
Cell junctions
 Advantage of Electrical synapses
• Faster communication.
– AP conduct directly through gap junctions.
– AP passes directly from presynaptic cell to postsynaptic cell.
• Synchronization.
– Coordinate the activity of group of neurons or muscle fibers.
– Large number of neurons or muscle fibers can produce
action potentials if they are connected by gap junctions.
– Coordinated contraction of these fibers to produce a
heartbeat or move food through the gastrointestinal tract.
 Chemical Synapses
• Presynaptic and postsynaptic neurons are separated by
synaptic cleft, a space of 20–50 nm that is filled with
interstitial fluid.
• Presynaptic neuron releases a neurotransmitter that
diffuses through the synaptic cleft and binds to
receptors in plasma membrane of postsynaptic neuron.
• Postsynaptic neuron receives chemical signal and in
turn produces a postsynaptic potential.
• Time required for chemical synapse, about 0.5 msec.
Synaptic transmission
 Synaptic transmission

One-way information transfer

Choline acetyltransferase

Nicotinic receptors Acetyl choline esterase

Acetyl choline
 Signal transmission at a
chemical synapse
• A nerve impulse reach end of a presynaptic axon.
– The depolarizing phase of nerve impulse opens voltage
gated Ca2+ channels.
– An increase concentration of Ca2+ move inside the
presynaptic neuron and triggers exocytosis of the
synaptic vesicles.
• The acetylcholine molecules in synaptic vesicles
diffuse across synaptic cleft and bind to receptors in
postsynaptic neuron’s.
 SYNAPTIC TRANSMISSION
• Acetylcholine bind to ligand-gated channels, which open
channels and allows Na+ ions to come inside the neuron.
• As ions flow through the opened channels, voltage across
the membrane changes.
– This change in membrane voltage cause postsynaptic
potential.

– Na+, which causes depolarization.

– Cl- or K+ channels causes hyperpolarization.
 Chemical Synapses
• Only one-way information transfer can occur —
from a presynaptic neuron to a postsynaptic neuron
or muscle fiber or a gland cell.

• Synaptic transmission at a neuromuscular junction

(NMJ) proceeds from a somatic motor neuron to a
skeletal muscle fiber.
 Excitatory and Inhibitory
Postsynaptic Potentials
• A neurotransmitter causes either an excitatory or an
inhibitory graded potential.

• A depolarizing postsynaptic potential is called an excitatory

postsynaptic potential. EPSP
– Acetylcholine, Epinephrine, Dopamine and Serotonin.

• A hyperpolarizing postsynaptic potential is termed an

inhibitory postsynaptic potential. IPSP
– γ amino butyric acid and Glycine.
 Removal of Neurotransmitter
• 1. Diffusion
– Diffuse away from the synaptic cleft
• 2. Enzymatic degradation
– Acetylcholinesterase breaks down acetylcholine
• 3. Uptake by cells.
– The membrane proteins that accomplish such uptake are
called neurotransmitter transporters.
 Agents which affect Neurotransmitter
S.No Name of Mode of action Mode of effect
substance
1 Botulinus toxin Block release of acetylcholine Total block of nerve impulse.
from presynaptic neurons

2 Curare Competes with acetylcholine Paralysis of respiratory muscle and

receptor on motor end plate death .

3 Neostigmine Inhibits acetylcholinesterase Prolong the action

4 Hemicholinium Block uptake of chloline into Depletes acetylcholine stores in

presynaptic terrminal presynaptic terrminal

In Myasthenia gravis – Ab are produced against acetyl choline receptor

cause skeletal muscle weakness and frangibility.
Curare used as a drug for Myasthenia gravis.
 Spatial and Temporal summation
• Spatial summation
– Buildup of neurotransmitter released simultaneously by
several presynaptic end bulbs.

• Temporal summation.
– Buildup of neurotransmitter released by a single
presynaptic end bulb two or more times in rapid
succession.
Spatial and Temporal Summation
Summation of signals
• A single postsynaptic
neuron receives input
from many presynaptic
neurons, some of
which release
excitatory
neurotransmitters and
some of which release
inhibitory
neurotransmitters.
 Integration of synapses
• Excitatory Post Synaptic Potential. (EPSP)
– If total excitatory effects are greater than inhibitory effects but less
than threshold level.
– Subsequent stimuli can generate a nerve impulse through summation
because partially depolarized.
• Nerve impulse.
– IF total excitatory effects are greater than the total inhibitory effects
and threshold is reached.
• Inhibitory Post Synaptic Potential (IPSP)
– total inhibitory effects are greater than the excitatory effects, the
membrane hyperpolarizes