ATP-SENSITIVE POTASSIUM CHANNEL MODULATION OF THE GUINEA-PIG VENTRICULAR ACTION-POTENTIAL AND CONTRACTION
ATP-SENSITIVE POTASSIUM CHANNEL MODULATION OF THE GUINEA-PIG VENTRICULAR ACTION-POTENTIAL AND CONTRACTION
复制标题
DOI：
10.1161/01.res.68.1.280
复制
发表时间：
1991-01-01
影响因子：
20.1
通讯作者：
LEDERER, WJ
中科院分区：
文献类型：
--
作者：
NICHOLS, CG;RIPOLL, C;LEDERER, WJ
本文研究了ATP敏感性钾（K（ATP））通道对豚鼠心室肌细胞动作电位和收缩的调节作用。 在电压钳下，通过将细胞暴露于完全代谢阻断（在10 mM 2-脱氧葡萄糖存在下的2 mM氰化物）来估计最大全细胞K（ATP）通道电导（195 +/- 10 nS，n = 6）。 在分离的由内而外的膜贴片中，测量了在相关条件下K（ATP）通道活性的ATP依赖性（在114 μ M下的半数最大抑制）。 在电流钳（细胞内ATP浓度= 5 mM）下，通过注入模拟K（ATP）电导的电流（与电压成比例）来估计分级K（ATP）通道激活对动作电位和颤搐的影响。 正如预期的那样，随着这种“电导”的增加，动作电位缩短，收缩幅度下降。 从这些实验的结果，定量依赖于细胞内ATP浓度的动作电位持续时间估计，而不依赖于细胞膜的数学模型。 结果意味着，如果ATP浓度低于正常水平（约5 mM），则可能会发生K（ATP）依赖性动作电位缩短，正如心肌缺血期间可能发生的局部或整体情况一样。
The role of ATP-sensitive potassium (K(ATP)) channels in modulating the action potential and contraction of guinea pig ventricular myocytes was investigated. Under voltage clamp, the maximum whole-cell K(ATP) channel conductance was estimated (195 +/- 10 nS, n = 6) by exposing the cells to complete metabolic blockade (2 mM cyanide in the presence of 10 mM 2-deoxy-glucose). In isolated inside-out membrane patches, the ATP dependence of K(ATP) channel activity under relevant conditions was measured (half-maximal inhibition at 114 mu-M). Under current clamp (with intracellular ATP concentration = 5 mM), the effect of graded K(ATP) channel activation on the action potential and the twitch was estimated by injection of a current (proportional to voltage) that simulated the K(ATP) conductance. As this "conductance" was increased, the action potential was shortened, and contractile amplitude declined, as expected. From the results of these experiments, the quantitative dependence of the action potential duration on intracellular ATP concentration was estimated, without relying on a mathematical model of the cell membrane. The results imply that K(ATP)-dependent action potential shortening is likely to occur if ATP concentration falls below normal levels (approximately 5 mM), as may happen regionally, or globally, during myocardial ischemia.