Cloning and functional expression of a rat heart K_ATP 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 diphosphates¹. 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 sulphonylureas² and for hypertension by activators such as pinacidil³. 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 heterogeneity¹. 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.