MOLECULAR-CLONING OF AN ATYPICAL VOLTAGE-GATED SODIUM-CHANNEL EXPRESSED IN HUMAN HEART AND UTERUS - EVIDENCE FOR A DISTINCT GENE FAMILY

Previously cloned voltage-dependent sodium channels exhibit a high degree of homology to one another and appear to comprise a single multigene family. We have now isolated and characterized cDNAs from both human adult heart and fetal skeletal muscle that encode a sodium channel-alpha subunit that exhibits only moderate primary structure identity with other sodium channels and is prominently expressed in both heart and uterus. The almost-equal-to 7.2-kilobase cDNA sequence, designated hNa(v)2.1, predicts a 1682-amino acid protein that bears 52 %, 49 %, and 46 % overall identity with sodium channels cloned from rat brain, skeletal muscle, and heart, respectively. Positively charged S4 segments are present in hNa(v)2.1, but there are fewer basic residues in repeat domains 1, 3, and 4 than in other cloned sodium channels. The cloning of hNa(v)2.1 provides evidence for greater evolutionary divergence among voltage-dependent sodium channels and suggests that other sodium channel gene subfamilies may exist. The unique amino acid sequences in regions known to be involved in voltage-dependent activation and inactivation suggest that hNa(v)2.1 will have novel gating properties.