肥厚左心室肌中层细胞Na+/Ca2+交换体电流及钾电流重构特征

目的 探讨肥厚左心室肌中层细胞Na⁺/Ca²⁺交换体电流(Na⁺/Ca²⁺ exchanger current,I_Na⁺/Ca²⁺)及钾电流重构特征,揭示心肌肥厚时心律失常发生的离子基础。方法 新西兰兔分为正常对照组及手术组各10只,手术组通过肾上腹主动脉次全缩窄诱发左室肥厚。采用全细胞膜片钳技术分别记录对照组及手术组左心室肌中层细胞的动作电位、I_Na⁺/Ca²⁺、慢激活的延迟整流钾电流(slowly activating delayed rectifier potassium current,I_Ks)、快激活的延迟整流钾电流(rapidly activating delayed rectifier potassium current,I_kr)等。结果 在基础刺激周长为2 s时,对照组和手术组的90%动作电位时程(90% action potential duration,APD90)分别为522.0±19.5 ms(n=6)、664.7±32.7 ms(n=7);在测试电位为+40 mV时,外向I_Na⁺/Ca²⁺密度在对照组及手术组分别为0.94±0.11 pA/pF(n=9)、1.30±0.11 pA/pF(n=8);在测试电位为-100 mV时,内向I_Na⁺/Ca²⁺密度在对照组及手术组分别为0.40±0.05 pA/pF(n=9)、0.56±0.02 pA/pF(n=8);在测试电位为+50 mV时,对照组及手术组的I_Ks尾电流密度分别为0.26±0.03 pA/pF(n=8),0.17±0.01 pA/pF(n=9);在测试电压为+50 mV时,对照组及手术组的I_kr尾电流密度分别为0.34±0.02 pA/pF(n=8),0.23±0.02 pA/pF(n=9),以上二者相比均有统计学意义。结论肥厚左心室肌中层细胞的电生理特性发生改变,表现为动作电位时间延长、I_Na⁺/Ca²⁺上调、I_Ks及I_kr下调。

Na+/Ca2+ exchanger current and K+ current remodeling in midmyocardial cells of hypertrophic left ventricle

Objective To investigate the characteristics of Na⁺/Ca²⁺ exchanger current (I_Na⁺/Ca²⁺) and K⁺ current remodeling in midmyocardial cells of hypertrophic left ventricle for understanding the ionic basis of arrhythmia of the hypertrophic heart. Methods Twenty New Zealand rabbits were divided equally into normal control group and operation group, and in the latter, left ventricular hypertrophy was induced in the rabbits by partial ligation of the abdominal aorta. Action potentials, I_Na⁺/Ca²⁺, slowly activating delayed rectifier K⁺ current (I_Ks) and rapidly activating delayed rectifier K⁺ current (I_Kr) were recorded in the two groups by using whole-cell patch-clamp technique. Results At the basic cycle length of 2 s, 90% action potential duration (APD₉₀) in control and operation groups was 522.0±19.5 ms (n=6) and 664.7±32.7 ms (n=7) respectively; at the testing potential of +40 mV, outward I_Na⁺/Ca²⁺ density in the two groups was 0.94±0.11 pA/pF (n=9) and 1.30±0.11 pA/pF (n=8) respectively; the testing potential of -100 mV elicited inward I_Na⁺/Ca²⁺ density of 0.40±0.05 pA/pF (n=9) and 0.56±0.02 pA/pF (n=8) respectively. The testing potential of +50 mV induced I_Ks tail current density of 0.26±0.03 pA/pF (n=8) and 0.17±0.01 pA/pF (n=9), and I_Kr tail current density of 0.34±0.02 pA/pF (n=8) and 0.23±0.02 pA/pF (n=9) respectively. Statistically significant differences were identified between the control and operation groups in all the above indices measured. Conclusion The characteristics of electrical remodeling changes in midmyocardial cells of hypertrophic left ventricle, exhibited by prolonged action potential, up-regulated I_Na⁺/Ca²⁺ and down-regulated I_Ks and I_Kr.