ON THE MECHANISM OF INHIBITION OF KATP CHANNELS BY GLIBENCLAMIDE IN RAT VENTRICULAR MYOCYTES

被引：42

作者：

RIPOLL, C ^{[1
]}

LEDERER, WJ ^{[1
]}

NICHOLS, CG ^{[1
]}

机构：

[1] WASHINGTON UNIV,SCH MED,DEPT CELL BIOL & PHYSIOL,660 S EUCLID AVE,ST LOUIS,MO 63110

来源：

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY | 1993年 / 4卷 / 01期

关键词：

ATP; ADP; CHANNELS; POTASSIUM CHANNELS; GLIBENCLAMIDE; SULFONYLUREAS; HEART; CARDIAC ELECTROPHYSIOLOGY;

D O I：

10.1111/j.1540-8167.1993.tb01210.x

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Introduction: The mechanism by which glibenclamide inhibits K(ATP) channel activity has been examined in membrane patches from isolated rat ventricular cells. Methods and Results: Inside-out patches were exposed to zero, or low, [ATP] to activate K(ATP) channels. Glibenclamide did not affect single channel conductance, but reversibly reduced channel open probability from either side of the membrane. Internal (cytoplasmic) glibenclamide inhibited with half-maximal inhibitory [glibenclamide] = 6 muM, Hill coefficient = 0.35. Complete channel inhibition was not observed, even at 300 muM [glibenclamide]. The response to step increases of internal [glibenclamide] could be resolved into two phases of channel inhibition (t1/2, fast < 1 sec, t1/2, slow = 10.5 +/- 0.9 sec, n = 8). Step decrease of [glibenclamide] caused a single resolvable phase of reactivation (t1/2 = 20.4 +/- 0.7 sec, n = 16). Channel inhibition by internal glibenclamide could be relieved by ADP, but only in the presence of Mg2+. Conclusion: Glibenclamide can inhibit K(ATP) channels from either side of the membrane, with block from one side being competitive with block from the other. Internal MgADP antagonizes the blocking action of glibenclamide. Glibenclamide inhibition of cardiac K(ATP) channels differs quantitatively and qualitatively from the inhibition of pancreatic K(ATP) channels.

引用

页码：38 / 47

页数：10

共 37 条

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