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Effects of ATP-sensitive K+ channel blockers on the action potential shortening in hypoxic and ischaemic myocardium.

Abstract：

:1. In order to determine whether activation of adenosine triphosphate (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 microM glibenclamide to almost the same extent, whereas it was increased by 100 microM pinacidil. 3. In guinea-pig papillary muscles a marked shortening of the action potential produced by 100 microM pinacidil was completely antagonized by 2 mM tolbutamide or 20 microM glibenclamide. 4. In guinea-pig papillary muscles exposed to hypoxic, glucose-free solution or dinitrophenol (10 microM)-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 microM 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.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Nakaya H,Takeda Y,Tohse N,Kanno M

doi

10.1111/j.1476-5381.1991.tb12294.x

subject

Has Abstract

pub_date

1991-05-01 00:00:00

pages

1019-26

issue

1

eissn

0007-1188

issn

1476-5381

journal_volume

103

pub_type

杂志文章

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