Potreau D, Gomez J P, Fares N
Laboratory of General Physiology, URA CNRS 1869, University of Poitiers, France.
Cardiovasc Res. 1995 Sep;30(3):440-8.
The aim of this study was to investigate transient outward potassium current (Ito) changes as a basis for the prolongation of the action potential associated with cardiac hypertrophy.
Right ventricular hypertrophy was induced by chronic pulmonary artery constriction in adult male ferrets. After 4-6 weeks, hearts were excised and single myocytes were isolated from the right ventricles of banded and sham-operated (control) animals by enzymatic dissociation. Ito was recorded by means of the whole cell patch clamp technique.
Heart weight:body weight ratio and cell membrane capacitance, as indications of hypertrophy, were increased by 17% (P < 0.05) and 32% (P < 0.01) respectively in the banded group. Analysis of Ito showed that in hypertrophied myocytes compared to normal controls: (1) the density of current was significantly reduced; (2) both the time to peak and the time constant of inactivation were increased; (3) the voltage-dependent steady-state availability was not changed, with similar potentials for half activation (30.4 +/- 6.8 mV in control and 33.9 +/- 8.5 mV in hypertrophied cells) and half inactivation (-12.3 +/- 3.3 mV in control and -11.4 +/- 2.7 mV in hypertrophied cells); (4) the time constant for recovery from inactivation was significantly increased regardless of the holding potentials (-50 mV, -70 mV or -90 mV).
Alterations of the transient outward potassium current with respect to its density, kinetics and recovery from inactivation can explain the prolongation of the action potential in myocytes isolated from pressure-overload hypertrophied heart and may thus be an important step in such cardiac adaptation.
本研究旨在探究瞬时外向钾电流（Ito）的变化，以此作为与心肌肥厚相关的动作电位延长的基础。
通过成年雄性雪貂的慢性肺动脉缩窄诱导右心室肥厚。4至6周后，切除心脏，并通过酶解从结扎和假手术（对照）动物的右心室中分离出单个心肌细胞。采用全细胞膜片钳技术记录Ito。
与对照组相比，结扎组的心脏重量与体重之比以及作为肥厚指标的细胞膜电容分别增加了17%（P < 0.05）和32%（P < 0.01）。Ito分析显示，与正常对照组相比，肥厚心肌细胞中：（1）电流密度显著降低；（2）峰值时间和失活时间常数均增加；（3）电压依赖性稳态可用性未改变，半激活电位（对照组为30.4±6.8 mV，肥厚细胞为33.9±8.5 mV）和半失活电位（对照组为-12.3±3.3 mV，肥厚细胞为-11.4±2.7 mV）相似；（4）无论钳制电位（-50 mV、-70 mV或-90 mV）如何，失活恢复的时间常数均显著增加。
瞬时外向钾电流在密度、动力学和失活恢复方面的改变可以解释压力超负荷肥厚心脏分离出的心肌细胞中动作电位的延长，因此可能是这种心脏适应过程中的重要一步。
