Japanese journal of pharmacology
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A variety of different isoforms of voltage-sensitive Na+ channels have now been identified. The recent three-dimensional analysis of Na+ channels has unveiled a unique and unexpected structure of the Na+ channel protein. Na+ channels can be classified into two categories on the basis of their amino acid sequence, Nav1 isoforms currently comprising nine highly homologous clones and Nax that possesses structure diverging from Nav1, especially in several critical functional motifs. ⋯ The demonstration of its dependence on Nav1.9 provides evidence for a specialized role of Nav1.9, together with Nav1.8, in pain sensation. Although Nax has not been successfully expressed in an exogenous system, recent investigations using relevant native tissues combined with gene-targeting have disclosed their unique "concentration"-sensitive but not voltage-sensitive roles. In this context, these emerging views of novel functions mediated by different types of Na+ channels are reviewed, to give a perspective for future research on the expanding family of Na+ channel clones.