Brooksby P, Levi A J, Jones J V
Department of Physiology, School of Medical Sciences, University of Bristol, UK.
J Hypertens. 1993 Jun;11(6):611-22. doi: 10.1097/00004872-199306000-00005.
Previous studies on multicellular preparations have shown that hypertrophied cardiac muscle from the spontaneously hypertensive rat (SHR) has a prolonged action potential. The first aim of the present study was to determine whether the action potential of isolated left ventricular myocytes was similarly prolonged and to study the underlying membrane currents that might be responsible. The second aim was to evaluate the L-type calcium current amplitude of SHR myocytes, as we have recently shown that they have an increased contraction and an increase in the calcium trigger entering via the L-type calcium channel might be one possible mechanism for this.
The electrophysiological characteristics of left ventricular myocytes isolated from the SHR were compared with those from normotensive control rats. Action potentials were recorded with microelectrodes. Cells were voltage-clamped and the membrane currents elicited by steps to different potentials were analysed. Blockers of potassium and calcium currents were used to reveal the contribution made by these currents to net membrane currents.
SHR myocytes had prolonged action potentials. The action potential duration of SHR myocytes at 90% repolarization was found to be longer, although at 20% and 50% repolarization no difference was found. There was no difference in the resting membrane potential between SHR and control myocytes. Using a voltage clamp we studied the L-type calcium current and potassium currents. The major change in SHR myocytes was a decrease in the magnitude (normalized to the membrane capacitance) of the inward rectifier potassium current elicited by negative potentials. There was no detectable difference in either the transient outward or delayed rectifier potassium currents. We also found no difference in the magnitude, time course or voltage dependence of L-type calcium current in hypertrophied SHR myocytes.
First, the action potential of SHR myocytes was prolonged compared with control myocytes. Secondly, the main change in SHR myocytes was that pulses to negative potentials elicited a lower inward rectifier potassium current. A reduction in the density of inward rectifier channels might play a role in prolonging the SHR action potential, since a lower outward repolarizing current will flow through inward rectifier potassium channels during the SHR action potential repolarization. Thirdly, there was no difference in L-type calcium current density or time course between SHR and control myocytes. Thus, a change in L-type calcium current probably plays no role in causing the prolonged SHR action potential or the increased contraction of hypertrophied SHR ventricular myocytes. Finally, the prolonged action potential in SHR myocytes may itself be one factor responsible for the increased contraction of these cells.
先前关于多细胞制剂的研究表明，自发性高血压大鼠（SHR）的肥厚心肌动作电位延长。本研究的首要目的是确定分离的左心室肌细胞的动作电位是否同样延长，并研究可能与之相关的潜在膜电流。第二个目的是评估SHR肌细胞的L型钙电流幅度，因为我们最近发现它们的收缩增强，而通过L型钙通道进入的钙触发信号增加可能是其一种可能机制。
将从SHR分离的左心室肌细胞的电生理特性与正常血压对照大鼠的进行比较。用微电极记录动作电位。对细胞进行电压钳制，并分析不同电位阶跃引发的膜电流。使用钾电流和钙电流阻滞剂来揭示这些电流对净膜电流的贡献。
SHR肌细胞的动作电位延长。发现SHR肌细胞在复极化90%时的动作电位持续时间更长，尽管在复极化20%和50%时未发现差异。SHR和对照肌细胞的静息膜电位没有差异。使用电压钳我们研究了L型钙电流和钾电流。SHR肌细胞的主要变化是负电位引发的内向整流钾电流幅度（相对于膜电容进行归一化）降低。瞬时外向钾电流或延迟整流钾电流均未检测到差异。我们还发现肥厚的SHR肌细胞中L型钙电流的幅度、时间进程或电压依赖性没有差异。
第一，与对照肌细胞相比，SHR肌细胞的动作电位延长。第二，SHR肌细胞的主要变化是负电位脉冲引发的内向整流钾电流较低。内向整流通道密度降低可能在延长SHR动作电位中起作用，因为在SHR动作电位复极化期间，较低的外向复极化电流将通过内向整流钾通道流动。第三，SHR和对照肌细胞之间的L型钙电流密度或时间进程没有差异。因此，L型钙电流的变化可能在导致SHR动作电位延长或肥厚的SHR心室肌细胞收缩增强方面不起作用。最后，SHR肌细胞中延长的动作电位本身可能是这些细胞收缩增强的一个因素。
