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比较从兔心脏房室结和心室分离的心肌细胞中延迟整流钾电流的特征。

Characteristics of the delayed rectifier K current compared in myocytes isolated from the atrioventricular node and ventricle of the rabbit heart.

作者信息

Howarth F C, Levi A J, Hancox J C

机构信息

Department of Physiology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK.

出版信息

Pflugers Arch. 1996 Mar;431(5):713-22. doi: 10.1007/BF02253834.

Abstract

The delayed rectifier potassium current (IK) is known to be important in action potential repolarisation and may contribute to the diastolic pacemaker depolarisation in pacemaker cells from the heart. In this study, using whole-cell patch clamp, we investigated the characteristics of IK in morphologically normal cells from the atrioventricular node (AVN) and ventricle of the rabbit heart. Cells were held at -40 mV and 5 microM external nifedipine was used to block L-type calcium current (ICa,L). Significant IK was observed with pulses to potentials more positive than -30 mV. The steady-state activation curve in both cell types showed maximal activation at between + 10 and + 20 mV. Half-maximal activation of IK occurred at -4.9 and -4.1 mV with slope factors of 8.3 and 12.4 mV in ventricular and AVN cells, respectively. Using pulses of increasing duration, significant IK tails after repolarisation from + 40 mV were observed with pulses of 20 ms and increased with pulses up to 100-120 ms in both cell types. Pulses of longer duration did not activate further IK and this suggested that only the rapid component of IK, called IKr, was present in either cell type. Moreover, IK tails after pulses to all potentials were blocked completely by E-4031, a selective blocker of IKr. The reversal potential of IK varied with the concentration of external K. Superfusion of AVN cells with medium containing 4, 15 and 40 mM [K+]o resulted in reversal potentials of -81, -56 and -32 mV, respectively, which are close to values predicted if the IK channel were highly selective for K. The time constants for deactivation of IK in ventricle and AVN on return to -40 mV after a 500-ms activating pulse to + 60 mV were 480 ms and 230 ms, respectively. The faster deactivation of IK in AVN cells was a distinguishing feature and suggests that there may be differences in the IKr channel protein between ventricular and AVN cells.

摘要

延迟整流钾电流(IK)在动作电位复极化过程中起着重要作用,可能参与心脏起搏细胞的舒张期起搏去极化过程。在本研究中,我们采用全细胞膜片钳技术,研究了兔心脏房室结(AVN)和心室中形态正常细胞的IK特性。细胞钳制在-40 mV,使用5 μM的硝苯地平阻断L型钙电流(ICa,L)。当去极化脉冲电位超过-30 mV时,可观察到明显的IK电流。两种细胞类型的稳态激活曲线均显示在+10至+20 mV之间达到最大激活。心室细胞和AVN细胞IK的半最大激活电位分别为-4.9 mV和-4.1 mV,斜率因子分别为8.3 mV和12.4 mV。使用持续时间逐渐增加的脉冲,在两种细胞类型中,从+40 mV复极化后,20 ms的脉冲可观察到明显的IK尾电流,且在100 - 120 ms的脉冲时IK尾电流增加。更长持续时间的脉冲不会进一步激活IK,这表明两种细胞类型中均仅存在IK的快速成分,即IKr。此外,E-4031(一种IKr的选择性阻滞剂)可完全阻断所有电位脉冲后的IK尾电流。IK的反转电位随细胞外K+浓度而变化。用含4 mM、15 mM和40 mM [K+]o的培养基灌流AVN细胞,分别导致反转电位为-81 mV、-56 mV和-32 mV,这些值接近如果IK通道对K+具有高度选择性时预测的值。在给予+60 mV的500 ms激活脉冲后,心室细胞和AVN细胞回到-40 mV时IK失活的时间常数分别为480 ms和230 ms。AVN细胞中IK更快的失活是一个显著特征,提示心室细胞和AVN细胞的IKr通道蛋白可能存在差异。

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