We have isolated a cDNA encoding an inwardly rectifying K+ channel (HH-IRK1) from human heart. The cDNA codes for a 427-amino acid protein, with two putative transmembrane domains and an H5 region. The primary structure of HH-IRK1 is homologous to that of the IRK1 channel cloned from a mouse macrophage-like cell line. Functional expression in Xenopus oocytes showed that HH-IRK1 is a K+ channel with strong inward rectification, blocked by extracellular Ba2+ and Cs+, and with a single-channel conductance of 30 pS. Northern analysis showed HH-IRK1 transcripts in human heart, brain, skeletal muscle, placenta, lung and kidney. HH-IRK1 was mapped to human chromosome 17.

We have identified several cDNAs for the human Kir5.1 subunit of inwardly rectifying K(+) channels. Alternative splicing of exon 3 and the usage of two alternative polyadenylation sites contribute to cDNA diversity. The hKir5.1 gene KCNJ16 is assigned to chromosomal region 17q23.1-24.2, and is separated by only 34 kb from the hKir2.1 gene (KCNJ2). In the brain, Kir5.1 mRNA is restricted to the evolutionary older parts of the hindbrain, midbrain and diencephalon and overlaps with Kir2.1 in the superior/inferior colliculus and the pontine region. In the kidney Kir5.1 and Kir2.1 are colocalized in the proximal tubule. When expressed in Xenopus oocytes, Kir5.1 is efficiently targeted to the cell surface and forms electrically silent channels together with Kir2.1, thus negatively controlling Kir2.1 channel activity in native cells.