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

Workman, A.J., MacKenzie, I. and Northover, B.J. (2000) Do K_ATP channels open as a prominent and early feature during ischaemia in the Langendorff-perfused rat heart? Basic Research in Cardiology, 95(3), pp. 250-260. (doi: 10.1007/s003950050188)

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 microM) 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 microM 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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Workman, Dr Antony
• Authors: Workman, A.J., MacKenzie, I., and Northover, B.J.
• Subjects: R Medicine > RC Internal medicine; Q Science > QP Physiology
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences
• Journal Name: Basic Research in Cardiology
• Publisher: Springer
• ISSN: 0300-8428
• Copyright Holders: Copyright © 2000 Springer