MEMBRANE POTENTIAL, GRADED POTENTIAL,

ACTION POTENTIAL AND DISORDERS OF MEMBRANE

POTENTIAL GENERATION AND PROPAGATION

Dr. Hafsa BashirMphil Physiology

OBJECTIVES

Mechanism of Resting Membrane potential Graded potential Action potential Phases of Action potential Propagation of the Action Potential

Membrane potential generation and propagation disorders

MEMBRANE POTENTIAL Membrane potential ( Transmembrane

potential Or Membrane voltage) It is the difference in electric potential

between the interior and the exterior of a biological cell.

With respect to the exterior of the cell, values of membrane potential range from –40 mV to –80 mV.

Interior of the cell is negatively charged in relation to the exterior

RESTING MEMBRANE POTENTIAL It is the potential difference existing across

the cell membrane at rest

RMP is maintained by:1. Natural concentration gradient2. Selective permeability of cell membrane3. Impermeable anions4. Sodium-potassium ATPase pump

MECHANISM: Neurons have a selectively permeable membrane

During resting conditions membrane is: permeable to potassium (K+) (channels are open) impermeable to sodium (Na+) (channels are closed)

Diffusion force pushes K+ out (concentration gradient) This creates a positively charged extra-cellular space. Electrostatic force pushes K+ in Thus, there is a ‘dynamic equilibrium’ with zero net

movement of ions.

The Resting Membrane Potential is Negative

ENVIRONMENTAL STIMULI CAUSE CHANGES IN THE MEMBRANE POTENTIAL BY OPENING GATED ION CHANNELS

Ligand-gated ion channels Voltage-gated ion channels Other-gated ion channels

(respond to mechanical, temperature, or other stimulus)

If membrane potential becomes more negative, it has hyperpolarized

e.g. -100mV is hyperpolarized

If membrane potential becomes less negative, it has depolarizede.g. -60mV is depolarized

GRADED POTENTIAL Graded Potentials or local potentials are

localized changes in the membrane potential (usually occurs at dendrites)

Graded = the magnitude of response is proportional to stimulus

Graded potentials summate (add together)

if summation of graded potentials reaches a threshold potential, they will generate an action potential.

If the neuron depolarizes to threshold potential (-55 mV), it results in an action potential

graded potentials may summate by:

1. Spatial Summation : If multiple dendrites of a neuron are stimulated

the depolarization of the dendrites are added together.

2.Temporal Summation : If a dendrite is stimulated at a high frequency it

results in a greater depolarization.

Graded Potentials are summated together at the Axon Hillock “Trigger Zone”

They arise from the summation of the individual actions of ligand-gated ion channel proteins,

They do not involve  voltage-gated sodium and potassium channels.  These impulses may be excitatory or inhibitory. They occur at the postsynaptic dendrite as a

result of presynaptic neuron firing and release of neurotransmitter.

Occur in skeletal, smooth, or cardiac muscle in

response to nerve input.

(a)Sub threshold depolarization will not result in an action potential.

(b)Summation of graded potentials may reach threshold stimulus, initiating an action potential at the trigger zone. The action potential begins when voltage-gated Na+ channels open at the trigger zone.

ACTION POTENTIAL  An action potential is a short-lasting event in

which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory.

Action potentials occur in neurons, muscle cells, and endocrine cells, in some plant cells.

In neurons, they play a central role in cell-to-cell communication.

In other types of cells, their main function is to activate intracellular processes.

In muscle cells, an action potential is the first step in the chain of events leading to contraction.

 Action potentials in neurons are also known as "nerve impulses" or "spikes"

THERE ARE 3 PHASES OF AN ACTION POTENTIAL

1. Depolarization Phase• Voltage-gated Na+ channels

open at -55mV (threshold stimulus)

• Na+ diffuses into cell

2. Repolarization Phase• Voltage-gated K+ channels open

at +30mV• K+ rushes out of the cell

repolarizing the membrane• Na+ channels close

3. Hyperpolarization Phase• The slower voltage-gated K+

channels remain open briefly, resulting in a slight hyperpolarization (-90mV).

(a) At rest, the membrane is polarized (RMP 70mV). Sodium is mostly outside the cell and potassium is within the cell.

(b) When the membrane depolarizes to threshold (-55mV), voltage-gated Na+ channels open. Sodium rapidly diffuses into the cell, depolarizing the membrane up to +30mV.

(c) As the membrane depolarizes to +30mV, voltage-gated K+ channels open and quickly repolarize the membrane. Sodium channels also close at this point.

Following an action potential, Na+/K+ pumps work to actively reestablish the Na+ and K+ concentration gradients.

Once initiated an action potential is propagated along the entire axon at full strength. It does not weaken.

PROPAGATION OF THE ACTION POTENTIAL An action potential in one region,

depolarizes the adjacent region to threshold stimulus (-55mV).

Once the adjacent region reaches threshold potential, it triggers another action potential.

The second action potential causes depolarization in its adjacent region, triggering yet another action potential.

This sequence continues all the way to the end of the axon at full strength.

All-Or-None Response

A stimulus stronger than threshold does not produce a stronger impulse (although a greater stimulation does produce more impulses per second)

If the axon hillock depolarizes to threshold potential it will initiate an action potential fully and completely.

e.g The action potential occurs fully and completely or not at all.

A stimulus below threshold is sub threshold and does not generate an action potential.

Refractory PeriodRefractory Period: For a brief period following an action potential, a threshold stimulus will not trigger another action potential.Absolute Refractory Period• no new action potentials can be produced• Occurs while the membrane is changing in sodium permeability• Occurs between the depolarization and repolarization phasesRelative Refractory Period• Action potential can be generated with a high intensity stimulus• Occurs while membrane is reestablishing its resting membrane potential• Lasts from the hyper polarization phase, until RMP is reestablished

MEMBRANE POTENTIAL GENERATION AND PROPAGATION

DISORDERS Hereditary spherocytosis (HS)

Tetrodotoxin (TTX)

Tetraethylammonium

Primary hyperkalemic paralysis

Tetany

MEMBRANE POTENTIAL GENERATION AND PROPAGATION

DISORDERSHereditary spherocytosis (HS) Plasma membrane of red cells three times

more permeable to Na+ The level of Na+,K+-ATPase elevated. When HS red blood cells have sufficient

glucose to maintain normal ATP levels, they extrude Na+ as rapidly as it diffuses into the cell cytosol. Hence the red blood cell volume is maintained.

When HS erythrocytes are delayed in the venous sinuses of the spleen, where glucose and ATP are present at low levels, the intracellular ATP concentration falls.

Therefore, Na+ cannot be pumped out by the Na+,K+-ATPase as rapidly as it enters.

The red blood cells swell - osmotic effect of elevated intracellular Na+ concentration.

Spleen targets these swollen erythrocytes for destruction - anemia.

Tetrodotoxin (TTX) Potent poison inhibits the firing of action

potentials in nerves by binding to the voltage gated sodium channels in nerve cell membranes and blocking the passage of sodium ions (responsible for the rising phase of an action potential) into the nerve cell.

Tetraethylammonium (TEA+), another poison, blocks the K+ channel when it is applied to the interior of the nerve fiber.

The ovaries of certain species of puffer fish, also known as blowfish, contain TTX. Raw puffer fish - Japan.

PRIMARY HYPERKALEMIC PARALYSIS In an inherited disorder, patients have episodes of

painful spontaneous muscle contractions, followed by periods of paralysis of the affected muscles.

Elevated levels of K+ in the plasma and extracellular fluid.

Some patients with this disorder have mutations of voltage-gated Na+ channels that result in a decreased rate of voltage inactivation.

This results in longer-lasting action potentials in skeletal muscle cells and increased K+ efflux during each action potential. This can raise the extracellular levels of K+.

The elevation of extracellular K+ causes depolarization of skeletal muscle cell.

As depolarization of the cells becomes more marked, the cells accommodate because of the voltage-inactivated Na+ channels.

Consequently, the cells become unable to fire action potentials and are unable to contract in response to action potentials in their motor axons.

TETANY

Hypocalcemia – sodium channels activated by very little increase of membrane potential from resting state

REFERENCES Guyton and Hall Textbook of Medical Physiology

12th edition

Ganong's Review of Medical Physiology 23rd edition

Berne & Levy Physiology 6th edition

Basics of Medical physiology by Dr.Venkatesh.D 3rd edition

Textbook Of Medical Physiology  by Indu Khurana 1st edition