Do KATP channels open as a prominent and early feature during ischaemia in the Langendorff-perfused rat heart? (original) (raw)

Abstract

The objective was to investigate whether myocardial adenosine triphosphate-sensitive K+ (KATP) 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 KATP 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 KATP channels had not opened during the ligation. The KATP 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 KATP blocker glibenclamide (1 μM) abolished both the APD-shortening and pro-arrhythmic effects of the KATP opener, both before and during coronary ligation, yet when delivered on its own, at the same concentration which abolished the effects of KATP 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, KATP channels do not open during early myocardial ischaemia.

Access this article

Log in via an institution

Subscribe and save

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Author information

Authors and Affiliations

  1. University Department of Medical Cardiology, Glasgow Royal Infirmary, 10 Alexandra Parade, Glasgow G31 2ER, UK, E-mail: A.J.Workman@clinmed.gla.ac.uk, , , , , , GB
    Antony J. Workman
  2. Covance Laboratories Ltd, Otley Road, Harrogate, North Yorks HG3 1PY, UK, , , , , , GB
    Ian MacKenzie
  3. Department of Pharmacology, School of Applied Sciences, De Montfort University, The Gateway, Leicester LE1 9BH, UK, , , , , , GB
    Basil J. Northover

Authors

  1. Antony J. Workman
  2. Ian MacKenzie
  3. Basil J. Northover

Additional information

Received: 24 September 1999, Returned for revision: 2 November 1999, Revision received: 21 December 1999, Accepted: 26 January 2000

Rights and permissions

About this article

Cite this article

Workman, A., MacKenzie, I. & Northover, B. Do KATP channels open as a prominent and early feature during ischaemia in the Langendorff-perfused rat heart?.Basic Res Cardiol 95, 250–260 (2000). https://doi.org/10.1007/s003950050188

Download citation