Generation of action potentials
Changes in the resting membrane potential determine whether action potentials are generated ( Ka.nd.e.l.et.,al 1991). Motor neurons have a resting membrane potential of -70 mV (intracellular negative), with a relatively high intracellular concentration of K + and a low intracellular concentration of Na+. This is maintained by Na+,
K+-ATPase, which pumps Na+ ions out of, and K+ ions into, the axon cytoplasm (CD Fig.ure..6). Depolarization, or a change to a less negative membrane potential, is excitatory. If a threshold level of depolarization is reached, an action potential is generated. Repolarization restores the membrane potential to its normal value after depolarization. Hyperpolarization generates a more negative membrane potential and decreases the likelihood of generating an action potential.
CD Figure 6. (a) The myelinated axon and the various regions of the axon surface in relation to the myelin (internode, paranode, or node of Ranvier) containing voltage-gated sodium channels (VGNaC), voltage-gated potassium channels (VGKC), or the Na +, K+ -ATPase pump. (b) A close-up of the axolemma and myelin depicting the localization of the two channels and pump.
The motor neuron has an extensive dendritic tree (Fig 3) which receives synaptic inputs from several sources, including the central processes of sensory axons, interneurons (largely inhibitory), and the descending pyramidal (corticospinal) motor pathway. These 'synaptic receptor potentials', produced by the interaction of neurotransmitters with receptors (chemically gated ion channels) on the motor neuron cell surface, produce local changes in the membrane potential ( Kandel et a.L
1991). Excitatory inputs, from Ia afferents mediating stretch reflexes and from descending corticospinal fibers, are probably mediated by the interaction of glutamate with receptors on dendritic spines, resulting in Na + influx and depolarization. Inhibitory inputs are mediated by the interaction of either glycine or GABA with receptors on the dendritic base or on the motor neuron cell body. This results in an influx of Cl causing hyperpolarization. Reflecting the spatial and temporal summation of these excitatory and inhibitory inputs, an integrative potential is generated at the axon hillock, the most proximal part of the peripheral process.
The action potential must somehow reach the nerve terminal. If the integrative potential produces sufficient depolarization to reach threshold, voltage-gated Na + channels in the axolemma open, and a depolarizing influx of Na+ produces an all-or-none action potential and the opening of still more Na + channels. Simultaneously, depolarization induces the opening of voltage-gated K + channels. The resultant efflux of K+ produces hyperpolarization. Although these two processes are initiated simultaneously, a delay in the opening of K+ channels permits an initial depolarization before the repolarizing K + efflux restores the membrane potential. Eventually, the concentrations of intracellular Na + and K+ are restored by the actions of Na+, K+-ATPase (CD Figure.. . . 6). Conduction velocity down the axon is increased in axons of larger diameter and in those insulated by myelin.
In the peripheral nervous system, Schwann cell processes form myelin. Voltage-gated Na + channels are concentrated at the nodes of Ranvier, which are gaps between Schwann cell processes (Fig, 3) (CD Figure. . .6). Voltage-gated K+ channels are located more diffusely in the axolemma under the myelin sheath of the paranode and internode. Additional ion channels in the axolemma modulate the balance between depolarization and repolarization ( Wa.x..m..a.Q 1993). These include distinct Na+, K+, and Ca2+ channels with specific localizations at the nodal, paranodal, or internodal axolemma under the myelin sheath, depending on their function.
Myelin increases the resistance to current loss through the surface of the axon, making conductance down the axon the path of least resistance and increasing conduction velocity. Larger axons have less resistance, also increasing the conduction velocity. Nevertheless, the amplitude of the action potential generated at the bare membrane of the axon hillock decays as it travels down the axon. However, if sufficient depolarization reaches the voltage-gated Na + channels concentrated at the node of Ranvier, an influx of Na+ further depolarizes the axon and regenerates the action potential ( KandeleLal 1991). Repeating this process at nodes every 1
to 2 mm further down the axon produces 'saltatory conduction' in myelinated fibers. Demyelination of peripheral nerves, as occurs in the Guillain-Barre syndrome, slows conduction and may result in conduction block, manifest clinically as weakness. In time, remyelination, or even redistribution of voltage-gated Na + channels over the full surface of the axolemma, may restore conduction. In some immune-mediated neuropathies, antibodies against myelin gangliosides may react with the extracellular portion of voltage-gated Na + channels, interfering with their function and impairing conduction.
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