7 - Altered Distributions and Functions of Multiple Sodium Channel Subtypes in Multiple Sclerosis and its Models

Abstract

This chapter reviews recent progresses made in the molecular analysis of sodium channels, both in experimental models of multiple sclerosis (MS) and in MS. Voltage-gated sodium (Na) channels plays an important roles in multiple sclerosis (MS). It is noted that under some circumstances, sodium channels can also play maladaptive roles in MS. Axonal degeneration is a major contributor to disability in MS and recent studies indicate that some sodium channels can support sustained ion fluxes, which can injure axons. Moreover, evidence suggests that switches in sodium channel expression i.e., deployment of the wrong subtype of sodium channel within a particular class of neurons can distort firing patterns and thus interfere with neuronal signaling in MS. Molecular analysis has shown that there are at least nine different genes encoding distinct voltage-gated sodium channels. Moreover, molecular identification and characterization of the sodium channel subtypes, or isoforms, that are expressed by neurons in the demyelinating diseases is critical to an understanding of the pathophysiology of MS and to the development of therapeutic strategies.