EFFECTS OF ATP-SENSITIVE K+ CHANNEL BLOCKERS ON THE ACTION-POTENTIAL SHORTENING IN HYPOXIC AND ISCHEMIC MYOCARDIUM

被引:89
作者
NAKAYA, H
TAKEDA, Y
TOHSE, N
KANNO, M
机构
[1] Department of Pharmacology, Hokkaido University School of Medicine, Sapporo
关键词
ATP-SENSITIVE K+ CHANNEL; GLIBENCLAMIDE; TOLBUTAMIDE; ACTION POTENTIAL SHORTENING; HYPOXIA; ISCHEMIA; CARDIAC MUSCLE;
D O I
10.1111/j.1476-5381.1991.tb12294.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 In order to determine whether activation of adenosine thriphosphate (ATP)-sensitive K+ channels exclusively explains the hypoxia- and ischaemia-induced action potential shortening, effects of tolbutamide and glibenclamide on changes in action potential duration (APD) during hypoxia, metabolic blockade or experimental ischaemia were examined in guinea-pig and canine isolated myocardium by standard microelectrode techniques. 2 With use of patch clamp techniques, activity of ATP-sensitive K+ channels was recorded from open cell-attached patches of guinea-pig isolated ventricular myocytes. The probability of opening of the K+ channels was decreased by 2 mM tolbutamide and 20-mu-M glibenclamide to almost the same extent, whereas it was increased by 100-mu-M pinacidil. 3 In guinea-pig papillary muscles a marked shortening of the action potential produced by 100-mu-M pinacidil was completely antagonized by 2 mM tolbutamide or 20-mu-M glibenclamide. 4 In guinea-pig papillary muscles exposed to hypoxic, glucose-free solution or dinitrophenol (10-mu-M)-containing, glucose-free solution, APD declined gradually and twitch tension decreased. Pretreatment with glibenclamide partially but significantly inhibited the action potential shortening, whereas tolbutamide failed to improve it during hypoxia or metabolic blockade. 5 When in canine isolated myocardium, experimental ischaemia was produced by the cessation of coronary perfusion, APD was gradually shortened. The action potential shortening was partially but not completely inhibited by pretreatment with 20-mu-M glibenclamide. 6 These results suggest that changes in membrane current(s) other than the outward current through ATP-sensitive K+ channels also contribute to the action potential shortening in hypoxic or ischaemic myocardium.
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页码:1019 / 1026
页数:8
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