Gene structures and expression profiles of three human KCND (Kv4) potassium channels mediating A-type currents I-TO and I-SA

The four known members of the KCND/Kv4 channel family encode voltage-gated potassium channels. Recent studies provide evidence that members of the Kv4 channel family are responsible for native, rapidly inactivating (A-type) c urrents described in heart (I-TO) and neurons (I-SA), In this study, we clo ned the human KCND1 cDNA, localized the KCND1 gene to chromosome Xp11.23-p1 1.3, and determined the genomic structure and tissue-specific expression of the KCND1, KCND2, and KCND3 genes, respectively. The open reading frame of Kv4.1 is 1941 nucleotides long, predicting a protein of 647 amino acids. T he deduced protein sequence of Kv4.1 shows an overall identity of 60% with Kv4.2 and Kv4.3L and corresponds to the common structure of voltage-gated p otassium channels, KCND1-specific transcripts were detectable in human brai n, heart, liver, kidney, thyroid gland, and pancreas, as revealed by Northe rn blot and RT-PCR experiments. The comparison of the expression patterns o f the known Kv4 family members shows subtype specificity with significant o verlaps, The KCND gene structures exhibit an evolutionarily conserved exon pattern with a large first exon containing the intracellular N-terminus and the putative membrane-spanning regions S1 to S5, as well as part of the po re region. The KCND3 gene contains an additional exon of 57 bp, which is no t present in the other two KCND genes and gives rise to the C-terminal spli ce KCND3L variant with an insertion of 19 amino acids. (C) 2000 Academic Pr ess.