IV. Membrane Potential and Action Potential

Membrane Potential

Other term form Transmembrane Potential
: electrical potentials across the membrane

Nerve and Muscle Cells are ____________________,

Excitable
: are capable of generating rapidly changing electrochemical impulses at their membrane.

Impulses transmit signal along

nerve or muscle membrane

Propagated electrical disturbance

Action Potential
: Sudden change in the normal resting membrane potential

The membrane potential existing during their resting period is called

Resting Membrane Potential (RMP)
: cell is not disturbed

Distribution of Solutes in Body Depends on

[1] Selective Permeability of Cell Membrane
[2] Available Transport Mechanism [Ion Channel]
[3] Water is in Osmotic Equilibrium
[4] Ions and Solutes are in Chemical Disequilibrium [Na-K Pump]
[5] Electrical Disequilibrium in ICF and ECF [+ICF; -ECF]

Diffusion Potential

Potential difference across a membrane because of a concentration difference of an ion.
: the driving force potential for Na to diffuse inside the cell
: allows for concentration gradient to occur

Example: Na diffusion potential

Equilibrium Potential

The diffusion potential that exactly balances (opposes) the tendency for diffusion caused by a concentration difference.

At electrochemical equilibrium, the chemical and electrical driving forces acting on an ion is

: equal and opposite and there is no more net movement.

Nernst Equation

Proposed by Walther Nernst
: Used to calculate the equilibrium potential for a concentration difference of a permeant ion across a cell membrane.

Ex: KCl in a solution of water

Resting Membrane Potential

: Measured potential differences across the cell membrane in mV.

· Intracellular potential relative to the extracellular potential.

· A resting membrane potential of -70 mV means 70 mV, cell negative (RMP of nerve)

Normal Resting Membrane Potential in Neuron

-70mV

Normal Resting Membrane Potential in Smooth Muscle

-60mV

Normal Resting Membrane Potential in Cardiac Muscle

-90mV

Resting Membrane Potential is Established by:

[1] Diffusion potential resulting from concentration difference of permeant ions

[2] Each permeant ion attempts to drive the membrane potential towards its equilibrium potential

[3] The Na-K pump contributes indirectly to the resting membrane potential by maintaining across the cell membrane the Na and K concentration gradients that then produce diffusion potentials.

Major Contributors of Resting Membrane Potential

[1] Diffusion of K ions and Na ions

[2] Leakage of K and Na ions through the nerve membrane via the K-Na leak channels

[3] K is more permeable than Na in leak channels

[4] Diffusion potentials alone caused by K and Na diffusion would give a membrane potential -86 mV (more K than Na)

K efflux primarily generates the electrical potential

varies between -50mV and -90mV in different types of cells

contribution of the Na-K pump to this potential is estimated at

about 5 to 20% of the total voltage.

K ions are more permeable than Na/ Ca ions because

the K concentration inside the cell is much higher than the outside concentration

Other Term for Na-K Pump

electrogenic pump

Na-K Pump

active at resting membrane potential and acts as a second force to generate negativity at the inner membrane surface

The Resting Membrane Potential is the sum of negative electrical potential differences generated by both

K ions and the Na, K pump

Na-K pump generates a

Generates a -1 charge;
: ICF is negative than ECF

Changes in Membrane Potential

1. Firing Threshold
2. Depolarization
3. Repolarization
4. Hyperpolarization

Firing Threshold

· the level of membrane potential at which sufficient depolarization has occurred to initiate an action potential

Depolarization

· the cell membrane potential becomes less polarized (+) (moves toward 0 mV from a negative potential level)

Repolarization

· the cell membrane potential becomes polarized again (-)(moves away from 0 mV to a more negative membrane potential)

Hyperpolarization

· the cell membrane becomes more polarized (negative) than the original resting membrane potential level.

Action Potential

· A property of excitable cells (nerve, muscle) consisting of a rapid depolarization [Na Influx in ICF] followed by repolarization [K Influx in ECF] of the membrane potential

: Have stereotypical size and shape, are propagating, and are all or none

Phases of Action Potential

1. Depolarization Phase
2. Overshoot
3. Repolarization
4. Hyperpolarization
5. Depolarization After Potential

Depolarization Phase

: upstroke or rising phase

· Membrane suddenly becomes very permeable to Na ions (influx of positive charge into the interior)

Action
: Once the Firing threshold is reached, this open for more Voltage Gated Ion Channel, thus, Na influx occur which causes Depolarization.

Upstroke of Action Potential

Inward Na current which causes depolarization

Inward current depolarizes the membrane potential to

threshold

Depolarization causes rapid opening of the activation gates of the

Na channel
: Na conductance of the membrane promptly increases

During Depolarization, what happens to the conductance of Na

The Na conductance becomes higher than K conductance and so the MP is driven toward the Na equilibrium potential of +65mV.

Generation of Action Potential in Nerve occurs where

o Initial segment of the axon

Reason why Action Potential is produced in Initial Segment

[1] Soma [Dendrites] has relatively few Voltage-Gated Na Channels in its membrane

[2] Initial Segment has numerous Voltage Gated Na channels

What Function that the Voltage Gated Na Channel play in the production of Action Potential

More Voltage Gated Na Channels allows more entry point for Na - which causes depolarization and the production of action potential within the cell.

Overshoot

- Positive Portion; Part of Depolarization: Exceeds Zero

: · Positivity due to inflow of Na ions

: MP "overshoot" beyond the zero levels and becomes positive

Repolarization

: re-establishment of the normal negative RMP (rapid diffusion of k ions to the exterior)

· closure of Na channels and opening of the K channels

Action
: Outward current of K from the ICF to the ECF via K Voltage Gated Channel; causes Repolarization

What causes depolarization and repolarization during Action Potential?

the Voltage-Gated Na channels and Voltage gated K channels

The combined effect of closing the Na channels and greater opening of the K channels make the K conductance

higher than Na conductance, and the membrane potential is repolarized.

Hyperpolarization

· MP becomes more negative than the original RMP for a few milliseconds after AP is over

Action
: The membrane becomes more negative; Normal RMP: -70mv. Hyperpolarization can exceed up into -80 or -90mv

Reason for hyperpolarization

K channels remain open for several ms after repolarization of the membrane is completed

Depolarizing After Potential

The Apparent of Na-K Pump
: Mechanism by which it restores the original number of Resting Membrane Potential to -70mv; this is done by Na-K pump by pumping 3Na from the ICF to the ECF and 2K from ECF to the ICF.

: A negative 1 charge is produced during this process.

Action Potential in Cell Types

Motor Neuron: 2 msecs
Skeletal Muscle: 5msec
Cardiac Muscle: 200msec

Kinds of Stimulus

1. Subthreshold
2. Threshold
3. Suprathreshold

Normal Resting Potential: -70mv

Subthreshold

· stimulus that fails to elicit AP
: Example - -60mv

Threshold

· stimulus that produces a full-length AP
: Example -55mv [Firing Threshold]

Suprathreshold

Stimulates that produces more AP; thus, can elicit an action potential

Stimulus: exceeds -55mv

Overview of the Transfer of Action Potential/ Na Channel

[TRANSFER FROM NEURON TO NEURON]
Neuron A contains action potential (Na+), to be transferred to Neuron B - Na ions enter the VGNa Channels [Few are present] to the Neuron B. [site of transfer - soma or dendrites]

The Na+ influx changes the membrane charge from negative to positive due to Na+. The stimulus comes from Neuron A - where Na+ influx is enough to reach the Firing Threshold [-55mv].

[FIRING THRESHOLD]
Reaching the Threshold will stimulate the opening of the MORE Voltage Channel present in Initial Segment.

In the Initial Segment, has more VGNa Channels. This will allow the influx of Na+ into the ICF, representing depolarization.

[DEPOLARIZATION]
More VGNa Channels means more entry point for Na+ causing depolarization. That is why, Initial Segment, can produce actual action potential. - Impulse Transmission.

Once equilibrium potential reached [0 or +35], the Na+ channel will close. This will stimulate the Voltage K+ Channel which allows influx of K+ from ICF to ECF, representing the Repolarization.

[REPOLARIZATION AND HYPERPOLARIZATION]
K+ Influx reaches the Membrane Potential [-55mv], however due the characteristic of the VGK Channel that slowly opens and close, this allows the excess of +K in the ECF [can reach -80mv to -90mv], representing hyperpolarization. Once reached, VGK+ Channel will close, ending hyperpolarization,

[Action of Na-K PUMP ]
Apparent Action of Na+K+ Pump will occur to restore the normal state of the Membrane Potential by transferring 3Na to the ECF and 2K in the ICF. The Net effect of this process is Negative 1.

2k-3Na= -1

Voltage Gated Sodium Channel [Na+ Channel]

Causes both depolarization and repolarization of the nerve membrane during action potential

Has 2 Gates
1. Activation Gates
2. Inactivation Gates

Excitation

· process of eliciting the AP

Factors that open the Na Channels

[1] Mechanical Disturbances of the membrane [Action Potential]

[2] Chemical effects on the membrane [Ions (Na+) and Neurotransmitter]

Na channels (Ca channels or both) will only re-open after depolarization

when the membrane potential returns either to or almost to the original RMP

Voltage Gated Potassium Channel (K+ Channel)

· Important in increasing the rapidity of repolarization of the membrane

· Has one gate inside the membrane

· Opens and closes outside

· Gate is closed during the resting stage (prevents efflux of K ions)

· Activated when the MP rises (+35 to -90mv)

· Opens very slowly (opens when Na channels are closing)

· Decrease in Na ions entry and simultaneous increase in K ions efflux from the cell, speed up re-polarization leading to full recovery of the RMP

Why do voltage-gated Na channels are activated before voltage gated K channels in response to a depolarizing stimulus?

Na channels are voltage sensitive than K channel

Na channel:
reacts at -55mv (firing threshold - stimulate voltage gated ion channels)

K channels:
occurs after depolarization
Reacts depending on 0 to 35+ mvv

Re-Establishment of Na and K Ionic Gradient is achieved through?

· Achieved by the action of the Na-K pump
: Na-K Pump will be stimulated if their excess Na+ inside the cell.

Refractory Period

Period of time after an AP during which another AP cannot be initiated.

: The continued inactivation of the voltage-gated Na channels after the firing of AP makes them unavailable for opening and provides the physiologic basis for the refractory period.

Function of Refractory Period

Protects the cell from over excitation by allowing a recovery period between AP in the same cell

Function of Refractory Period in Neural Cells

protects the cell from the hyper-repetitive firing of AP;

: result in pathologies such as seizures.

Function of Refractory Period in Cardiac Ventricular Cells

prevents repetitive AP;

: trigger a rapid heart rate (tachycardia) or disorganized cell-to-cell conduction patterns in cardiac arrhythmias and death

Two Types of Refractory Period

1. Absolute Refractory Period
2. Relative Refractory Period

Absolute Refractory Period

No chance of Action Potential to occur; Na channel is in inactivated state

: The inactivation gates of the Na channels are closed and will remain closed until repolarization occurs. No AP can occur until the inactivation gates open.

No matter how large the stimulus, a second action potential cannot be produced.

Absolute Refractory Period

Relative Refractory Period

Refers to the time period immediately after an AP, when a second AP can be triggered if a suprathreshold stimulus is applied

: · The K conductance is higher than at rest, the MP is closer to the K equilibrium potential and farther from the threshold; more current is required to bring the membrane to threshold.

A stronger-than-threshold stimulus can initiate another action potential

Relative Refractory Period

Reasons of Refractiveness

[1] Some of sodium channels have not been reversed from their inactivation state

[2] K channels are usually wide open causing greatly excess flow of K ions to the outside

Inhibition of Excitability

[1] Membrane Stabilizing Factor
: high ECF Ca ions decrease membrane permeability to sodium

[2] Local Anesthetic

Travels in all direction away from the stimulus until the entire membrane has become depolarized

Action Potential

Resting Membrane Potential (RMP) of Nerves

-70 mv [average size neuron]

Nerve signals are transmitted by

action potential, which are rapid changes in the membrane potential that spread rapidly along the nerve fiber membrane.

Special Aspects of Signal Transmission in Nerve Trunks

1. Myelinated Nerve Fiber (large fiber)/ MEDULLATED NERVE FIBER

2. Unmyelinated Nerve Fiber (small fiber)/ N0N-MEDULLATED NERVE FIBER

Myelinated Nerve Fiber

Myelin Sheath present; CNS: Oligodendrocytes; fast transmission due to myelin sheath; Node of Ranvier - conduct action potential

Unmyelinated Nerve Fiber

PNS: Schwann Cells; the action potential needs to travel each segment

Saltatory Conduction (Myelinated)

[1] Conduction of AP from node to node
[2] Nerve impulse jumps from node to node
[3] Increases the velocity of nerve transmission
[4] Conserve energy
[5] Accomplished almost through the sodium channels

The axons of some nerves are populated by cells called

[1] Oligodendrocytes (Brain and spinal cord) or
[2] Schwann cells (peripheral nerves).

Why do voltage-gated Na channels activate before voltage gated K channels in response to a depolarizing stimulus?

Na channels are more voltage-sensitive than K channels

Action Potential in Nerve Cells

must fire rapidly and repetitively to transmit electrical impulses throughout the nervous system.

: Their AP reflects this functional requirement, showing rapid changes in potential and a short duration

: Voltage-gated neuronal type of Ca channels is also activated during the AP, and the resulting Ca influx provides the signal for neurotransmitter release

Action Potential in Cardiac Muscle

: contract and relax the cardiac ventricles at a relatively slow rate of 60 to 90 times per minute.

: voltage gated Na and K channels contribute to the depolarization and repolarization phases of the cardiac AP, similar to their role in excitation of neuronal cells.

: The plasma membrane of the cardiac muscle cells expresses a different type of voltage gated Ca channel than found in neuronal cells.

: This Ca influx, coupled to the release of Ca from intracellular stores, provides the activator Ca required for the vigorous contraction and accounts for the long plateau phase of the AP.

Calcium channel

· responsible for plateau of the AP (slow, prolonged opening)

Rhythmicity

· Repetitive self-induced discharge occurring in some excitable tissues (smooth muscle, some neurons of the CNS

: Caused by the permeability of the membrane to sodium ions to allow automatic membrane depolarization

Causes of Rhythmicity

1. Rhythmical beat of the heart
2. Peristalsis of the intestine
3. Neuronal events (rhythmical control of breathing)

Action Potential in Smooth Muscle Cell

populates a heterogeneous group of tissues, including blood vessels, bladder, uterus and GIT.

: Their electrical properties vary greatly among different tissues.

: Setting of their resting potential at less negative potentials between -45 and -60 mV.

smooth muscle cells rely primarily on

voltage gated Ca channels for electrical excitation.

: responsible for the upstroke of AP in smooth muscle and provides Ca for muscle contraction. These AP maybe sustained or of spiking configuration.