PMID: 2504288Aug 21, 1989Paper

Effects of tolbutamide, glibenclamide and diazoxide upon action potentials recorded from rat ventricular muscle

Biochimica Et Biophysica Acta
J F Faivre, I Findlay

Abstract

Drugs which influence the electrical activity of insulin-secreting B cells of mammalian islets of Langerhans by closing (tolbutamide and glibenclamide) or opening (diazoxide) ATP-sensitive potassium channels were applied to the ventricular muscle of the rat. Action potentials were recorded from ventricular epicardium of perfused intact rat hearts. Tolbutamide (0.5-2.0 mM), glibenclamide (0.01-0.1 mM) and diazoxide (0.5 mM) each evoked a dose-dependent increase (7-33%) in the duration of the ventricular action potential measured at 50% of repolarization. These drugs were without effect upon the resting membrane potential or the peak of the action potential. Single-channel recordings of ATP-sensitive K+ channels were obtained from excised membrane patches of enzymatically isolated rat ventricular myocytes. Tolbutamide and diazoxide inhibited openings of ATP-sensitive K+ channels. Diazoxide inhibited ATP-sensitive K+ channel openings in the presence of ATP. Diazoxide did not evoke opening of ATP-sensitive K+ channels. It is concluded that these drugs could act to increase the duration of the cardiac action potential by inhibiting openings of ATP-sensitive K+ channels.

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Citations

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Nov 1, 1992·Pflügers Archiv : European journal of physiology·B Allard, M Lazdunski
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