Evolution of voltage-gated Na+ channels

Voltage-gated Na(+) channels play important functional roles in the generation of electrical excitability in most vertebrate and invertebrate species. These channels are members of a superfamily that includes voltage-gated K(+), voltage-gated Ca(2+) and cyclic-nucleotide-gated channels. There are nine genes encoding voltage-gated Na(+) channels in mammals, with a tenth homologous gene that has not been shown to encode a functional channel. Other vertebrate and invertebrate species have a smaller number of Na(+) channel genes. The mammalian genes can be classified into five branches in a phylogenetic tree, and they are localized on four chromosomes. Four of the branches representing the four chromosomal locations probably resulted from the chromosomal duplications that led to the four Hox gene clusters. These duplications occurred close to the emergence of the first vertebrates. The fifth branch probably evolved from a separate ancestral Na(+) channel gene. There are two branches in the invertebrate tree, although members of only one of those branches have been demonstrated to encode functional voltage-gated Na(+) channels. It is possible that the other branch may have diverged, so that its members do not represent true voltage-gated Na(+) channels. Vertebrate and invertebrate Na(+) channels appear to be derived from a single primordial channel that subsequently evolved independently in the two lineages.