Na⁺ Channel Reorganization in Demyelinated Axons

It is noted that the normal myelinated axons, ion channels are localized with a high level of precision in specific regions. Voltage-dependent Na+ channels are sequestered at high density at initial segments and within the nodal gap. Myelin damage has consequences beyond the resulting deficits in passive cable properties, and reorganization of ion channels is important in both acute and chronic phases. Na+ channel clusters have a high degree of stability, no doubt resulting from their link to the underlying cytoskeleton by ankyrinG, and perhaps the specialized form of spectrin present at these sites. Nonetheless, these channels ultimately disperse or are internalized, and must be restored. The low density internodal pool of Na+ channels appears to serve this purpose on short time scales. The reorganization of ion channels that follows demyelination is of prime importance in determining the neurological deficits that result, and perhaps even the survival of the axon itself. Knowledge of the precise mechanism of these events can provide new targets for therapies aimed at restricting and perhaps reversing the functional loss that is a consequence of demyelinating disease.