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 beta-cells is a complex of Kir6.2, a member of the inwardly rectifying potassium channel superfamily, and the sulfonylurea receptor. We have isolated cDNA clones encoding rat Kir6.2. Co-expression of rat Kir6.2 and sulfonylurea receptor in human embryonic kidney cells generated a potassium current with the properties of the beta-cell ATP-sensitive potassium 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 rats, whereas there was no significant change in sulfonylurea receptor mRNA levels. Thus, decreased expression of Kir6.2 could contribute to the beta-cell dysfunction which characterizes diabetes mellitus in this animal model.