RAT INWARDLY RECTIFYING POTASSIUM CHANNEL KIR6.2 - CLONING, ELECTROPHYSIOLOGICAL CHARACTERIZATION, AND DECREASED EXPRESSION IN PANCREATIC-ISLETS OF MALE ZUCKER DIABETIC FATTY RATS

The ATP-sensitive potassium channel of insulin-secreting pancreatic be ta-cells is a complex of Kir6.2, a member of the inwardly rectifying p otassium channel superfamily, and the sulfonylurea receptor. We have i solated cDNA clones encoding rat Kir6.2. Co-expression of rat Kir6.2 a nd sulfonylurea receptor in human embryonic kidney cells generated a p otassium current with the properties of the beta-cell ATP-sensitive po tassium channel. A quantitative reverse transcriptase-polymerase chain reaction assay indicated that Kir6.2 and sulfonylurea receptor mRNAs were abundantly expressed in rat islets and that expression of Kir6.2 mRNA was reduced by >70% in islets from Zucker diabetic fatty male rat s, whereas there was no significant change in sulfonylurea receptor mR NA levels. Thus, decreased expression of Kir6.2 could contribute to th e beta-cell dysfunction which characterizes diabetes mellitus in this animal model. (C) 1996 Academic Press, Inc.