The Action Potential Revision of the Resting Membrane Potential

The Action Potential Revision of the Resting membrane potential

1. Intracellular concentration of K+ is neurones is high and Na+ is low relative to the extracellular space 2. The reversal potential is the potential towards which the membrane would move if it was freely permeable to this particular ion, and no other ions. At this potential chemical driving force is exactly equal electrical driving force and the net ion flux in nill. 3. The reversal potential for K+ ions in neurones is very negative (~ -95 mV) while for Na+ ions positive (~ +60 mV). 4. Resting membrane potential is generated mainly by a steady flux of K+ ions through ion channels embedded into the membrane of the neurone. Dr Sergey Kasparov School of Medical Sciences, Room E9

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Real action potentials What is the action potential?

AP is a brief “all-or-none” depolarisation of the neuronal Amplifier membrane which, once initiated propagates without decrement. 0 mV

Movie - Nervous communication -60 mV One second

Action potentials are very fast changes in membrane potential from negative inside the cell to positive and back.

Features of the AP – 1: Features of the AP – 2: Propagation along the cell’s membrane and along the “All-on-none” nature axon

Amplifier Amplifier 1 Amplifier 2 Amplifier 3

Amp 1

One second Amp 2

Amp 3 In contrast to the “small, sub-threshold” potentials, action potentials have very similar amplitude and shape. Once the threshold has been reached, their amplitude will not increase even if a stronger stimulus is Time applied. In terms of information transfer they are like logic “ones”, as compared to “zeros”.

1 Glossary of the terms Ionic basis of AP: Na ions are responsible for depolarisation, K ions are responsible for re-polarisation. Fluxes of both ions are coordinated by voltage-gated ion channels.

Overshoot

RRepolarisationepolarisation

Hyperpolarisation

Depolarisation

Resting membrane potential

+ Na channels are controlled by the potential of the membrane. “Positive feedback” is responsible for the very fast dynamics of AP

Na+ Na+ Voltage sensor and Na+ activation mechanism Na+ Na+ Outside of the cell

1. Depolarisation 2. Opening of voltage-gated Aqueous pore Na+ channels Extracellular domain

Lipid membrane 3. Sodium currents Intracellular depolarise membrane narrow selectivity filter domain further “Inactivation gate”

Inside the cell (negative)

Something has to happen for this process to terminate!

At positive potentials voltage-gated Na+ channels become “inactivated”

Voltage sensor and Na+ Outside of the cell activation mechanism Na+ Na+

Aqueous pore

Extracellular domain

Lipid membrane

Intracellular domain narrow selectivity filter Na+ current is responsible for the “Inactivation gate” upstroke of the action potential

Na+ Na+ Na+

2 Ion channel activation during an action potential

mV 50

REMEMBER: 0 Na+ fluxes depolarise the membrane (EP ~+60), K+ fluxes hyperpolarise the --5050 membrane (EP ~-90)

--100100 time

K+ channels opening

Na+ channels opening

Na+ channels inactivate

Molecular nature of the voltage-gated Na+ and K+ channels Two factors responsible for AP termination:

1. Inactivation of Na+ channels

2. Delayed activation of K+ channels (delayed rectifiers)

A voltage-gated Na channel is formed by association of 4 main (α) subunits

Refractory periods A) Absolute refractor period (second AP cannot occur under any circumstance) B) Relative refractory period (a stronger-than-normal stimulus may evoke an AP) Absolute Relative mV 50

0

--5050

--100100 time K+ channels opening

Na+ channels opening

Na+ channels inactivate

3 Saltatory conduction of AP, Schwann cells and oligodendroglia Saltatory conduction of AP, Schwann cells and oligodendrocytes

Schwann cells are responsible for myelinisation in peripheral nerves

In the CNS myelin is provided by oligodendrocytes

1. Axons of many types of neurones are “insulated” with multiple layers of myelin. 2. Bare “gaps” between the insulated parts are known as nods of Ranvier. 3. This is known as saltatory conduction. AP “jump” from one node to the next one as electrical field, rather than a wave of Na+ channel openings. 4. This greatly accelerates AP propagation and saves much energy.

What happens at “the end” – action potentials lead to release Speed of conductance depends on the degree of myelinisation. of transmitter from pre-synaptic terminals. “Thick” vs “thin” axons.

1. Axons of different types of central and peripheral neurones have different degree of myelinisation.

2. Axons with thick myelin insulation are generally faster and can conduct at Movie AP1 many tens of meters/second. Un-myelinated (or almost un-myelinated) axons can be as slow as 1 m/sec. Movie Fancy neurones 3. Loss of myelin occurs in many diseases, for example multiple sclerosis. This may be fatal. Movie - Chemical synapse

Summary

1. Features of AP 2. Ionic basis of AP 3. Basic mechanism of AP propagation 3. Saltatory conduction and the role of myelin

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