ATP-dependent potassium channel in rat cardiomyocytes is blocked by lidocaine - Possible impact on the antiarrhythmic action of lidocaine
ATP-dependent potassium channel in rat cardiomyocytes is blocked by lidocaine - Possible impact on the antiarrhythmic action of lidocaine
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DOI：
10.1161/01.cir.93.4.656
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发表时间：
1996-02-15
期刊：
影响因子：
37.8
通讯作者：
Vogel, W
中科院分区：
文献类型：
--
作者：
Olschewski, A;Brau, ME;Vogel, W
背景利多卡因在心肌缺血时具有良好的抗心律失常作用。恶性心律失常是由于缺血区和非缺血区细胞外钾离子浓度和动作电位时程的异质性所致。这些作用归因于ATP依赖性钾（K-ATP）通道的激活。在这项研究中，我们研究了利多卡因对K-ATP通道的作用，以测试利多卡因的抗心律失常特性和其对K-ATP通道的作用之间可能存在的联系。方法和结果膜片钳技术employed酶分离的成年大鼠心肌细胞。通过多管灌注系统将利多卡因应用于切除的膜补片的外侧。利多卡因以浓度依赖性方式可逆地阻断K-ATP通道的平均电流（TC 50 =43+/-4.7 μ mol/L，E=0 mV，n=6），而单通道电流的幅度保持不变。半最大阻断浓度对应于治疗范围的抗心律失常应用的利多卡因bolus在humans.Conclusions的开放概率，但不是电导的K-ATP通道在大鼠心肌细胞膜被利多卡因阻断。这种作用可以部分解释利多卡因在急性心肌缺血时的有利抗心律失常特性。
Background During myocardial ischemia, lidocaine has favorable antiarrhythmic properties. Malignant arrhythmias result from heterogeneity between ischemic and nonischemic regions in extracellular potassium concentration and action potential duration. These effects have been attributed to the activation of ATP-dependent potassium (K-ATP) channels. In this study, we investigated the action of lidocaine on the K-ATP channels to test the possible link between the antiarrhythmic properties of lidocaine and its action on the K-ATP channel.Methods and Results The patch-clamp technique was em ployed on enzymatic dissociated cardiomyocytes of adult rats. Lidocaine was applied to the outer side of excised membrane patches by means of a multibarrel perfusion system. Lidocaine reversibly blocked the mean current of the K-ATP channels in a concentration-dependent manner (TC50=43+/-4.7 mu mol/L, E=0 mV, n=6), while the amplitude of the single-channel current remained unchanged. The half-maximum blocking concentration corresponds to the therapeutic range for the antiarrhythmic application of a lidocaine bolus in humans.Conclusions The open probability but not the conductance of the K-ATP channel in the membrane of rat cardiomyocytes is blocked by lidocaine. This action may explain, in part, the favor able antiarrhythmic properties of lidocaine during acute myocardial ischemia.