Isolation and chromosomal localization of a human ATP-regulated potassium channel

Abstract

K_ATP channels are K⁺ channels whose activity is inhibited by the presence of and enhanced by the absence of cytosolic ATP. This property allows K_ATP channels to sense cellular intermediary metabolism and directly couple this information to the modulation of membrane excitability. Indeed, recent studies from our laboratory and others have suggested that activation of K_ATP channels during anoxia is important in the response and adaptation of central neurons to hypoxia. In order to identify K_ATP channels from human brain, we performed a polymerase chain reaction (PCR) using human cerebral cortex mRNA and primers derived from the ROMK1 sequence, a cDNA clone encoding an ATP-regulated potassium channel, recently isolated from rat kidney. We thus identified a novel 308-bp PCR product, pKCNJ1, whose expression was found to be restricted to a 3.0-kb band in the kidney by probing a human multiple tissue northern blot. pKCNJ1 was then used to isolate genomic clones and, using fluorescence in situ hybridization (FISH) to human metaphase chromosomes, was mapped to chromosome 11q.