Over ten different mammalian genes related to the Drosophila Shaker gene (the Sh gene family) have been identified recently. These genes encode subunits of voltage-dependent K+ channels. The family consists of four subfamilies: ShI genes are homologues of Shaker; ShII, ShIII, and ShIV are homologues of three other Shaker-like genes in Drosophila, Shab, Shaw, and Shal, respectively. We report here the cloning of a human K+ channel ShIII cDNA (HKShIIIC) obtained from a brain stem cDNA library. HKShIIIC transcripts express an atypical voltage-dependent transient (A-type) K+ current in Xenopus oocytes. This current is activated by large membrane depolarizations and is extremely sensitive to the K+ channel blocker TEA unlike most A-type currents. The gene encoding HKShIIIC maps to chromosome 1p21.

Genomic and cDNA clones encoding a novel Shaw-related potassium channel gene have been isolated from mice and humans. The mouse-Kv3.3 gene encodes a protein of 679 amino acids. Unlike the vertebrate Shaker-related genes that have intronless coding regions, mouse Kv3.3 is encoded by at least two exons separated by 3 kb of intervening sequence. The amino-terminal 212 amino acids are encoded by a single exon, and the hydrophobic core of the protein beginning at the S1 transmembrane segment is contained in a separate exon. Multiple Kv3.3-hybridizing transcripts are visible in the mouse brain, liver, thymus, and heart. Using probes derived from a human genomic clone containing the 3' exon of human Kv3.3 (KCNC3), we have localized the gene to human chromosome 19. The related gene, human Kv3.4 (KCNC4), was localized to human chromosome 1.