Cloning of a novel four repeat protein related to voltage-gated sodium and calcium channels

Cloning has led to the discovery of more ion channels than predicted by functional studies, yet there remain channels that have not been cloned. We report the cloning of a novel protein that contains the four domain structure found in voltage-gated Ca2+ and Na+ channels, Phylogenetic relationships suggested that the protein might have diverged from an ancestral four repeat channel before the divergence of Ca2+ and Na+ channels. Northern blot analysis showed that mRNA transcripts encoding the protein are expressed predominantly in the brain, moderately in the heart, and weakly in the pancreas. Despite extensive expression attempts, currents from the putative channel were not detected, Based on its sequence, we propose that the novel protein might be a voltage-activated cation channel with unique gating properties. (C) 1999 Federation of European Biochemical Societies.