McIntosh M A, Cobbe S M, Kane K A, Rankin A C
Department of Medical Cardiology, Royal Infirmary, Glasgow University, UK.
J Mol Cell Cardiol. 1998 Jan;30(1):43-53. doi: 10.1006/jmcc.1997.0570.
We have studied the action potential characteristics and potassium currents in single left ventricular myocytes isolated from control and hypertrophied rabbit hearts. Left-ventricular hypertrophy (LVH) was induced following perinephritis-induced hypertension. Control animals underwent a sham operation. Animals were killed at 10 weeks post-operation. Left-ventricular myocytes were isolated by an enzyme dissociation technique. Action potential duration (APD) at 50 and 90% repolarisation was prolonged in myocytes obtained from hypertrophied compared to control hearts over the range of stimulation frequencies (0.1-1.5 Hz). This prolongation in APD was more pronounced in epicardial compared to endocardial myocytes. Steady-state ionic current, measured at the end of voltage clamp steps of 3-s duration, stepping at intervals of 10 mV, from a holding potential of -40 mV, was similar in control and hypertrophied myocytes. However, when normalised for capacitative cell surface area, steady-state current was significantly smaller in hypertrophied myocytes over the voltage range -40 to -60 mV and at potentials greater than +10 mV. Inward rectifier potassium current (IKl), identified as the barium chloride (0.1 mM)-sensitive current, contributed to the steady state current at negative potentials. Normalised IKl was significantly smaller in hypertrophied compared to control myocytes at potentials negative to -60 mV. Peak transient outward potassium current (Ito) density was reduced in hypertrophied compared to control myocytes at 0 and +10 mV, from a holding potential -80 mV (12.9 +/- 2.3 v 24.9 +/- 3.9 microA cm2, at +10 mV, P < 0.05). Steady-state inactivation of Ito was similar in control and hypertrophied myocytes. In conclusion, LVH induced by perinephritis hypertension in the rabbit is associated with a prolongation in APD. Reductions in IKl, sustained outward current and Ito may contribute to the prolongation in APD.
我们研究了从对照和肥厚兔心脏分离出的单个左心室肌细胞的动作电位特征和钾电流。通过肾周炎诱导的高血压诱导左心室肥厚(LVH)。对照动物接受假手术。术后10周处死动物。采用酶解离技术分离左心室肌细胞。在刺激频率范围(0.1 - 1.5 Hz)内,与对照心脏相比,从肥厚心脏获得的肌细胞在复极化50%和90%时的动作电位时程(APD)延长。与心内膜肌细胞相比,这种APD的延长在心外膜肌细胞中更明显。在持续3秒的电压钳制步骤结束时测量的稳态离子电流,从 - 40 mV的钳制电位开始,以10 mV的间隔步进,在对照和肥厚肌细胞中相似。然而,当以电容性细胞表面积进行归一化时,在 - 40至 - 60 mV的电压范围内以及电位大于 + 10 mV时,肥厚肌细胞中的稳态电流明显较小。内向整流钾电流(IKl),被鉴定为对氯化钡(0.1 mM)敏感的电流,在负电位时对稳态电流有贡献。在电位负于 - 60 mV时,与对照肌细胞相比,肥厚肌细胞中归一化的IKl明显较小。从 - 80 mV的钳制电位开始,在0和 + 10 mV时,与对照肌细胞相比,肥厚肌细胞中的峰值瞬时外向钾电流(Ito)密度降低(在 + 10 mV时为12.9 +/- 2.3对24.9 +/- 3.9 μA/cm²,P < 0.05)。对照和肥厚肌细胞中Ito的稳态失活相似。总之,兔肾周炎高血压诱导的LVH与APD延长有关。IKl、持续外向电流和Ito的降低可能导致APD延长。