Protection of cardiomyocytes by pinacidil during metabolic inhibition and hyperkalemia.
The objective of this study is to understand the mechanism underlying the cardioprotective effects of pinacidil, an ATP-sensitive K+ channel (K(ATP)) opener. We examined the effects of 10 microM pinacidil in cultured chicken cardiomyocytes. Pinacidil caused a concentration-dependent delay in metabolic inhibition-induced increase in intracellular calcium concentration ([Ca2+]i) and creatine phosphokinase release, and this action was antagonized by glyburide, a K(ATP) blocker. Neither verapamil, an L-type Ca2+ channel blocker, nor bepridil, a Na+-Ca2+ exchange inhibitor, affected the time course of increase in [Ca2+]i induced by metabolic inhibition. Pinacidil did not have an effect on the amplitude of K+-induced increase in [Ca2+]i, but accelerated the rate of decline following peak stimulation. In contrast, glyburide reduced the amplitude of K+-induced increase in [Ca2+]i and prolonged the rate of decline. These results provide direct evidence that pinacidil protects cardiomyocytes from metabolic inhibition-induced injury by cyanide (CN) through a delay in the onset of increase in [Ca2+]i, rather than by inhibition of the L-type Ca2+-channels or by alteration of Na+-Ca2+ exchange.
Tang
T
T
Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine at Peoria, 61656, USA.
Dong
C
C
Duffield
R
R
Ho
A K
AK
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D015764:Bepridil / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D002642:Chick Embryo; D003402:Creatine Kinase / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology; D006706:Homeostasis; D006947:Hyperkalemia / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D020110:Pinacidil / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D011189:Potassium Chloride / Q000494:pharmacology; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015221:Potassium Channels; D019831:Sodium-Calcium Exchanger; D011189:Potassium Chloride; D015764:Bepridil; D020110:Pinacidil; D000255:Adenosine Triphosphate; D014700:Verapamil; D003402:Creatine Kinase; D005905:Glyburide; D002118:Calcium