Phylogenetic analysis of alpha chains of voltage-gated ion channels revealed that extensive gene duplication has occurred among both Ca(2+) and Na(+)-channels since the origin of vertebrates. Rather than showing a pattern of gene duplication consistent with the hypothesis of polyploidization early in vertebrate history, both Ca(2+) and Na(+) channels showed patterns of sequential gene duplication associated with specialization of the gene products. In the case of Na(+) channels, the phylogeny supported the hypothesis that the ancestral vertebrate gene had an expression pattern including both central and peripheral nervous system cells and that duplication of vertebrate Na(+) channel genes has repeatedly been followed by specialization for the central nervous system, the peripheral nervous system, or muscle cells. Thus, cephalization in vertebrate evolution has been accompanied by specialization of this important family of neuromuscular proteins along the central-peripheral axis.