Potassium accumulation in the globally ischemic mammalian heart. A role for the ATP-sensitive potassium channel.
We investigated the contribution of opening of the ATP-sensitive K+ channel to extracellular accumulation of K+ during ischemia with the use of glibenclamide, a specific blocker of this K+ channel. To characterize the electrophysiological effects of glibenclamide during metabolic inhibition (by either application of dinitrophenol or hypoxia) we performed patch-clamp studies in isolated membrane patches of guinea pig myocytes and in intact guinea pig myocytes and studied action potential parameters in isolated superfused guinea pig papillary muscle. We studied the effect of glibenclamide on extracellular accumulation of K+ and H+ in isolated retrogradely perfused globally ischemic hearts of rat, guinea pig, and rabbit. Experimental evidence is presented that supports the conclusions that glibenclamide 1) effectively blocks open K+ATP channels, 2) reverses the dinitrophenol-induced increase of the outward current and prevents the hypoxia-induced shortening of the action potential, 3) decreases the rate of K+ accumulation during the first minutes of ischemia in stimulated hearts, an effect which was entirely absent in quiescent hearts, and 4) does not influence the rate and extent of ischemia-induced extracellular acidification.
Wilde
A A
AA
Department of Cardiology and Experimental Cardiology, University of Amsterdam, The Netherlands.
Escande
D
D
Schumacher
C A
CA
Thuringer
D
D
Mestre
M
M
Fiolet
J W
JW
Janse
M J
MJ
D000200:Action Potentials / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D003327:Coronary Disease / Q000503:physiopathology*; D004140:Dinitrophenols / Q000494:pharmacology; D004553:Electric Conductivity; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D005905:Glyburide / Q000494:pharmacology*; D006168:Guinea Pigs; D000860:Hypoxia / Q000503:physiopathology; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010210:Papillary Muscles / Q000503:physiopathology; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains
D004140:Dinitrophenols; D015221:Potassium Channels; D000255:Adenosine Triphosphate; D011188:Potassium; D005905:Glyburide