CLONING AND FUNCTIONAL EXPRESSION OF A RAT-HEART K-ATP CHANNEL

POTASSIUM channels that are ATP-sensitive (K-ATP) couple membrane pote ntial to the metabolic status of the cell. K-ATP channels are inhibite d by intracellular ATP and are stimulated by intracellular nucleotide diphosphates(1). K-ATP channel are important regulators of secretory p rocesses and muscle contraction, and are targets for therapeutic treat ment of type II diabetes by the inhibitory sulphonylureas(2) and for h ypertension by activators such as pinacidil(3). In cardiac tissue, K-A TP channels are central regulators of post-ischaemic cardioprotection( 4,5). Electrophysiological and pharmacological characteristics vary am ong K-ATP channels recorded from diverse tissues suggesting extensive molecular heterogeneity(1) A complementary DNA encoding a K-ATP channe l was isolated from rat heart using the polymerase chain reaction. We report here that the expressed channels possess all of the essential f eatures of native cardiac K-ATP channels, including sensitivity to int racellular nucleotides. In addition the cloned channels are activated by the potassium channel opener, pinacidil, but are not inhibited by t he sulphonylurea, glibenclamide.