Department of Life SciencesUniversity of CalicutKerala, India 673 635

Electrical potential exist cross the membranes of all cellsSome cells are excitableK+ concentration is greater inside the cell than outsideK+ moves out of the cell Negative ions remain inside which prevent further movement of K+ to the outsidePotential difference in large mammalian neurons is 94mv -negative inside

Na + ions are more outside than inside Membrane is highly permeable to Na+ Na + moves to the inside- inside become more positiveNa + movement makes outside negative and inside positiveNow the potential difference is 61 mv with positive inside

Membrane PotentialsResting membrane potential

in a mammalian nerve cell is -90mv

Sodium –potassium pump – Na+ to outside and K+ to inside

Electronegative pump- more positive charge pumped to outside than to inside

3Na+ to outside for 2 K+ to inside

Large concentration gradient of K+ and Na+ inside and outside

Electrochemical gradient

Na+ (outside cell) – 142mEq/LNa+ (inside cell) –14mEq/L

K+ (outside cell) – 4mEq/LK+ (inside cell) –140mEq/L

Channel proteins in restK+ and Na+ ions leak through channel proteinsPotassium-sodium leak channelsMore K+ leak – 100 times than Na+

Channels and pumps

Action potentialNerve signals are transmitted by action potentialsAP is a rapid change in the membrane potentialAP spreads rapidly along the nerve membraneSudden change from negative potential to positive

potential

Resting stage

Membrane remain polarised

Postential at this stage is -70mV

Depolarisation:Membrane is very permeable to Na+ ions- large number of

Na+ moves into the cellCharge inside become neutralPotential rise in Positive direction – this is called

depolaristion

Some fibers, the potential overshoots and reach positive value

RepolarisationThe Na+ channel begin to

closeK+ channels open more

than normalRapid diffusion of K+ to the

exteriorReestablish the normal

negative potential

Voltage gated channelsVoltage gated Na+ channels play a major role in

depolarisation and repolarisation during action potential Voltage gated K+ channels also play major role in speeding

up the repolarisationThese are in addition to the Na+-K+ pump and the Na+-K+

leak channels

Voltage gated Na+ channels

Voltage gated Na+ channel –activation-inactivation

AS voltage reach between -70 and -50- sudden conformational change in activation gate

Gate opensThis is activated state of the gateNa+ flow into the cell Na+ permeability increase 500-5000 foldAfter a few 10,000ths of a second the inactivation gate closesNa+ can not move into the cellRepolarisation starts channels can open only after reaching resting potential

stage

Voltage gated K+ channelsDuring resting state the K+ channel remain closedK+ can not pass out of the cell through the membraneAs membrane potential goes up from -90 – gate opens

slowlyK+ diffuse outAs opening of K+ is slow by the Time they are open Na+ channels Begin to closeThis cause repolarisation

Action PotentialsAn action potential occurs when there is a reversal of

the normal resting potential, going from negative to positive. Also called depolarization.

Depolarization occurs when a stimulus causes the voltage-gated Na+ channels to open, allowing Na+ to rapidly influx down its concentration gradient.

The sudden in-rush of positive sodium ions reverses the membrane potential for a few milliseconds.

Then the voltage-gated K+ channels open, allowing K+ to rapidly efflux due to its concentration gradient. This brings the membrane back to negative inside and is called repolarization.

Action PotentialsEven though the voltage has returned to

negative, the membrane is not at resting potential because it now has too much Na+ inside and not enough K+ ions.

The presence of high Na+ inside causes the Na+/K+ pumps to increase by a power of 3. The faster pump rate quickly restores the membrane back to its steady-state resting condition.

Sodium channels have 2 gates, a normal voltage (activation) gate (which is closed at rest) and an inactivation gate (which is open at rest). The rapid opening of the voltage gate lets Na+ rush in and depolarizes the cell. This is immediately followed by closing of the inactivation gate which stops the Na+ influx. At the same time the K+ gate opens letting K+ efflux (repolarization).

Widmaier, et al., 2006