Molecular studies of two voltage-dependent sodium channels expressed in the nervous system

The action potential in most excitable cells is generated in response to the rapid opening and closing of the voltage-sensitive sodium channel. In vertebrate skeletal muscle and brain this channel consists of a large, glycosylated alpha subunit (approximately 260 kDa) and one or two smaller beta subunits (approximately 35-40 kDa). The alpha subunit is encoded by a large multi-gene family, the members of which are expressed in a tissue-specific manner. Two of the genes, encoding the type I and II sodium channels, are expressed at high levels within the central nervous system. We have performed experiments showing that genetic components responsible for neural specificity of these sodium channel genes is located upstream of the promoters. In particular, negatively-acting elements have been identified which repress sodium channel gene expression in non-neural cell lines. Identification of the proteins which mediate neural-specific expression should prove useful for genetic manipulation of sodium channel expression in vivo, and for providing a molecular framework for understanding neural-specific expression in general.