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

Abstract

The objective was to investigate whether myocardial adenosine triphosphate-sensitive K⁺ (K_ATP) channels open during the first 10 min of regional ischaemia in Langendorff-perfused rat hearts. Changes in monophasic action potentials 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 duration (APD). The APD₅₀ and APD₈₀ (15.5 ± 1.0 and 38.1 ± 2.3 ms, respectively [mean ± S.E., n = 15 hearts], immediately prior to ligation) increased transiently during the first 4 min of ligation (by 160 and 79% respectively, 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 possibility that the myocardial K_ATP channels had not opened during the ligation. The K_ATP opener Ro 31-6930 (0.5 and 5 μM) shortened the APD₅₀ and APD₈₀ during coronary ligation, to significantly below both their control and pre-occlusion values (P < 0.05), and caused a concentration-dependent increase in both the incidence and duration of VT during the ligation. Ro 31-6930 at 5 μM also shortened APD₅₀ and APD₈₀ even before ligation (by 50 and 62% respectively, P < 0.05), and abolished the normal APD-lengthening seen during ischaemia. The K_ATP blocker glibenclamide (1 μM) abolished 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 ligation alone. These results suggest that, in Langendorff-perfused rat hearts in the absence of drugs, K_ATP channels do not open during early myocardial ischaemia.