The evolution of voltage-gated sodium channels as interpreted from a study of sodium currents and channels from the hydrozoan jellyfish, Polyorchis penicillatus

Voltage-gated sodium channels are responsible for the rapid depolarization of membranes that leads to propagated action potentials. Sodium channels are considered to be the most recently evolved member of the voltage-gated ion channel superfamily, probably derived from Ca2+ channels. Sodium channels likely evolved to mediate high frequency signaling and rapid propagation to coordinate the activities of multicellular organisms, and thus may have been coincident with the appearance of the Metazoa.; Cnidarians are the simplest eumetazoans with a discrete nervous system and rapid, transient Na+ currents. Cnidarians are considered to have split from the main lineage early in metazoan evolution and thus are uniquely suited for providing clues to the evolution of Na+ channels.; Sodium currents in the hydromedusa, Polyorchis penicillatus were shown to be unusually insensitive to classical Na+ channel drugs, like tetrodotoxin, but neither are they sensitive to Ca2+ channel drugs. Two electrophysiologically distinct Na+ currents were described in swimming motor neurons and "B neurons". Nonetheless, only one full-length Na+ channel cDNA could be found from P. penicillatus. The 5.8 kb cDNA has major structural features of typical Na+ channels, especially in areas responsible for ion selectivity, voltage-sensing, fast-inactivation and glycosylation. The 13.9 kb gene that spanned the full-length revealed that 85% of the introns were found to partition the coding region in the homologous position of mammalian Na+ channels. One of these introns is spliced by a rare U12-type spliceosome conserved in P. penicillatus and most Ca 2+ and Na+ channels. Intron positions found in mammalian genes but not the jellyfish gene correspond to highly variable regions which were rich in structural motifs for glycosylation, phosphorylation and binding to cytoplasmic proteins.; Similarity of features between jellyfish and mammalian Na+ channels extends from the exon-intron structure of the gene, the different splicing mechanisms, the structure of the cDNA to the electrophysiological properties of recorded currents. Overall, this Ph.D. research strongly suggests that the organization and fundamental composition of the genetic template for Na+ channels has undergone few changes since it was laid down in the common ancestors of diploblasts and triploblasts, ∼600 million to 1 billion years ago.