Mitochondrial ATP‐sensitive K + channels, protectors of the heart

ATP-sensitive K+ (KATP) channels were first identified in the sarcolemma of cardiac myocytes as inwardly rectifying K+ channels that were inhibited by intracellular ATP (Noma, 1983). It was proposed that KATP channels would have a cardioprotective effect during ischaemia by shortening action potential duration and thereby decreasing Ca2+ influx into myocytes. Then it was found that K+ channel opener compounds (KCOs), that are known to activate sarcolemmal KATP channels, exert cardioprotective effects under ischaemia–reperfusion (Grover et al. 1989; Grover & Garlid, 2000). However, several groups of investigators found that KCOs exerted cardioprotection at concentrations below those causing action potential shortening (Yao & Gross, 1994; Grover et al. 1995a,b; Garlid et al. 1997), indicating that KCOs may have targets other than sarcolemmal KATP channels. Alternative targets for KCOs include mitochondrial KATP (mitoKATP) channels (Grover & Garlid, 2000).