Cloning and functional expression of a rat heart KATP channel

POTASSIUM channels that are ATP-sensitive (K ATP ) couple membrane potential to the metabolic status of the cell. K ATP channels are inhibited by intracellular ATP and are stimulated by intracellular nucleotide diphosphates 1 . K ATP channels are important regulators of secretory processes and muscle contraction, and are targets for therapeutic treatment of type II diabetes by the inhibitory sulphonylureas 2 and for hypertension by activators such as pinacidil 3 . In cardiac tissue, K ATP channels are central regulators of post-ischaemic cardioprotection 4,5 . Electrophysiological and pharmacological characteristics vary among K ATP channels recorded from diverse tissues suggesting extensive molecular heterogeneity 1 . A complementary DNA encoding a K ATP channel was isolated from rat heart using the polymerase chain reaction. We report here that the expressed channels possess all of the essential features of native cardiac K ATP channels, including sensitivity to intracellular nucleotides. In addition the cloned channels are activated by the potassium channel opener, pinacidil, but are not inhibited by the sulphonylurea, glibenclamide.