Do K-ATP channels open as a prominent and early feature during ischaemia in the Langendorff-perfused rat heart?

The objective was to investigate whether myocardial adenosine triphosphate- sensitive K+ (K-ATP) channels open during the first 10 min of regional isch aemia in Langendorff-perfused rat hearts. Changes in monophasic action pote ntials and arrhythmias were studied during myocardial ischaemia in both the presence and absence of pharmacological K-ATP modulation. Ligation of the left main coronary artery for 10 min did not shorten the action potential d uration (APD). The APD(50) and APD(80) (15.5 +/- 1.0 and 38.1 +/- 2.3 ms, r espectively [mean +/- S.E., n = 15 hearts], immediately prior to ligation) increased transiently during the first 4 min of ligation (by 160 and 79% re spectively, P < 0.05), before returning to pre-ligation values, but without a significant below-baseline-shortening. The cardiac electrogram showed no accompanying ventricular tachyarrhythmia (VT). These results raised the po ssibility that the myocardial K-ATP channels had not opened during the liga tion. The K-ATP opener Ro 31-6930 (0.5 and 5 mu M) shortened the APD(50) an d APD(80) during coronary ligation, to significantly below both their contr ol and pre-occlusion values (P < 0.05), and caused a concentration-dependen t increase in both the incidence and duration of VT during the ligation. Ro 31-6930 at 5 mu M also shortened APD(50) and APD(80) even before ligation (by 50 and 62% respectively, P < 0.05), and abolished the normal APD-length ening seen during ischaemia. The K-ATP blacker glibenclamide (1 mu M) aboli shed both the APD-shortening and pro-arrhythmic effects of the K-ATP opener , both before and during coronary ligation, yet when delivered on its own, at the same concentration which abolished the effects of K-ATP activation, it had no significant effect on the APD changes seen during the coronary li gation alone. These results suggest that, in Langendorff-perfused rat heart s in the absence of drugs, K-ATP channels do not open during early myocardi al ischaemia.