Hypoxia-induced activation of katp-channels limits energy depletion in the guinea pig heart. Decking, U. K. M., T. Reffelmann, J. Schrader, and H. Kammermeier. Institut f[umlaut]ur Herz und Kreislaufphysiologie, Heinrich-Heine -Universit[umlaut]at D[umlaut]usseldorf, 40225 D[umlaut]usseldorfand Institut f[umlaut]ur Physiologie, RWTH Aachen, 52057 Aachen
APStracts 2:0084H, 1995.
The functional role of ATP-dependent potassium channels (KATP) in hypoxic cardiac failure was investigated in isolated guinea pig hearts using glibenclamide and rimalkalim as inhibitor and activator, respectively. Monophasic action potential duration at 90% of repolarization (MAP90%), left ventricular function and cardiac energy status (31P NMR spectroscopy) were measured during normoxic (95% O2) and hypoxic (20% O2) perfusion. In normoxic hearts, 1 [mu]M glibenclamide did not affect MAP90%, left ventricular pressure (LVP) and coronary flow (n=4). In contrast, rimalkalim rapidly shortened MAP90% and LVP in a dose-dependant fashion. This latter effect was reversed by 1 [mu]M glibenclamide (n=4). Hypoxic perfusion reduced LVP accompanied by a shortening of the action potential (MAP90%) (202+/-13 vs. 164+/-9 ms) and an increase in coronary flow. Glibenclamide (1 [mu]M) reversed the MAP90% shortening and the increase in coronary flow. In addition, glibenclamide increased LVP transiently (n=4). When coronary flow of hypoxic hearts was kept constant, however, glibenclamide elicited a sustained positive inotropic effect (n=7). LVP increased from 54+/-4 to 64+/-3 mmHg following glibenclamide accompanied by a reduction in the free energy change of ATP hydrolysis (GATP) from -54.5+/-1.9 to -52.9+/-0.2 kJ/mol and a further increase in the coronary venous adenosine from 269+/-48 to 1680+/-670 nmol/l. In contrast, rimalkalim (0.1 [mu]M) further shortened the action potential of hypoxic hearts and caused a major reduction of systolic force. This was accompanied by a partial restoration of GATP (-55.8+/-0.7 kJ/mol) and decrease in venous adenosine (157+/-27 nmol/l). Our results suggest that KATP-channels are activated during hypoxia when there are only small changes in cytosolic ATP. This channel activation contributes to the down -regulation of contractile force. It is proposed that hypoxia-induced activation of KATP-channels constitutes a protective mechanism which conserves the cardiac energy status under conditions of insufficient oxygen supply. 

Received 25 May 1994; accepted in final form 25 January 1995.
APS Manuscript Number H454-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 21 March 1995.