Nerve conduction corresponds to the generation of action potential propagation.

1. Mechanism of action potential formation:

An action potential is associated with a massive and abrupt influx of sodium ions through channels

Fast Nav channels (INat current, t for transient).

• Massive influx of sodium ions = depolarization of the membrane potential.
• Positive values for the nerve fiber
• Depolarization followed by an outflow of K+ ions through the opening of potassium channels, known as delayed rectification.
• Repolarization is dependent for most nerve fibers.
• Also, other mechanisms involved in repolarization.

2.Stages of the action potential:

1: Depolarization =

Following an initial depolarization that exceeds the activation threshold for opening fast Nav channels:

• There is opening of these channels, massive passage of sodium ions, according to their concentration gradient
• This current is called INat.

2: Repolarization =

Inactivation of fast sodium channels

• 3 possible configurations: closed, open, and inactive
• After their opening, these Nav channels enter an inactivated state,
• Sodium can no longer pass through the channel.
• This corresponds to a refractory period lasting approximately 3ms in humans.

Leak currents through the myelin sheath = bb currents (Barrette and Barrette)

• charges the myelin sheath like a battery
• just after the action potential is emitted, they can re-excite the node of Ranvier = this is the post-potential depolarization (DAB)
• phase of excitability of the nerve fiber = supernormal period
• 7 ms after the emission of the action potential
• no generation of a second action potential

3.Return to resting potential:

Paranodal potassium channels: supernormal period =

• Limits the phenomenon of re-excitation
• Located between the myelin sheath and the node of Ranvier (between the internodal and nodal regions)
• Rapid kinetics, responsible for a IKf current (f for fast)
• Outflow of potassium = hence a tendency for hyperpolarization
• Will counteract this period of great excitability linked to post-potential depolarization
• Balance between the phenomenon of post-potential depolarization and potassium leakage through paranodal potassium channels

Slow potassium channels responsible for an IKs current =

• post-potential hyperpolarization = late subnormal period.

Return to resting potential =

• After 150 ms.

4.Emission of action potential:

All-or-nothing law =

• The emission of the action potential in a nerve fiber follows the all-or-nothing law.
• Either the resting membrane potential reaches the action potential threshold, and an action potential will be emitted.
• Either this threshold is not reached, and there is no emission of action potential.

Fixed amplitude =

• The action potentials on a given nerve fiber have a fixed amplitude.
• The coding of the nerve impulse will not be based on variations in action potential amplitude.
• It is done through variations in frequency or the discharge pattern of these action potentials.
• Thus, it is this frequency and discharge pattern that will convey the information that will be transmitted in the nervous system.

5.Path of the action potential:

Myelinated fibers =

From node of Ranvier to node of Ranvier:

• Sodium channels are only expressed at the node of Ranvier
• no fast sodium channels under the myelin sheath

Orthodromic direction:

• conduction of the nerve impulse only occurs in one direction
• from the cell body of the axon to the axon terminal.

Unmyelinated fibers =

Electronic conduction

• In contrast, for an unmyelinated fiber, sodium and potassium channels are expressed along the entire axon,
• there are no BB currents nor post-potential depolarization phenomena,
• Conduction speed is much lower than for a myelinated fiber

6.Regulation of action potential:

Na+/K+-ATPase pump =

Mechanism:

• exchanges 3 sodium ions for 2 potassium ions
• process that consumes ATP

Pathologies:

• If the pump cannot function fully, sodium cannot exit after entering during the action potential.
• Accumulation of sodium in the axon cannot be sustained.

The Na+/Ca+ antiport =

• In the absence of energy resources, the axon will engage a Na+/Ca+ antiport that translocates Na+ against Ca+ without requiring energy.
• Through this exchanger, Na+ will be able to exit but Ca+ will enter.
• Ca+ inside a cell can have beneficial effects but also harmful effects in a pathological situation = cell death
• This is a state of excitotoxicity that occurs in many metabolic, ischemic, inflammatory, or metabolic situations.

The ratio of nerve conduction speed therefore of action potential propagation is around

1/100.

7.Conduction speed of fibers:

• Unmyelinated = One or a few m/s
• Myelinated = Several tens up to a hundred m/s
• These conduction speeds are also influenced by various factors such as temperature, activity, and environmental factors like pH.

Diameter:

• The larger and longer the myelin segments, the faster this saltatory conduction will be.

Nerve fibers, depending on their diameter, do not transmit the same type of information:

• Information related to balance and deep nerve sensitivity is conveyed by very large nerve fibers up to 100/s.
• Sensitivity to heat and cold is conveyed by small nerve fibers, including unmyelinated ones, at 1 to a few m/s.

8.Therapeutic Goals:

• Highlighting alterations in terms of fiber loss or myelin alterations in neuropathic pathological situations.