Effects of tolbutamide, glibenclamide and diazoxide upon action potentials recorded from rat ventricular muscle.
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.
Faivre
J F
JF
Laboratoire de Physiologie, Comparée CNRS UA 1121, Université de Paris XI, Orsay, France.
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D000200:Action Potentials / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D003981:Diazoxide / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D014044:Tolbutamide / Q000494:pharmacology*
D015221:Potassium Channels; D000255:Adenosine Triphosphate; D014044:Tolbutamide; D003981:Diazoxide; D005905:Glyburide