持续性心房颤动患者心房肌细胞L型钙通道电流变化的研究

Research of L-type Ca^(2+) channel current in atrial myocytes of patients with chronic atrial fibrillation

目的比较窦性心律(窦律)患者和持续性心房颤动(房颤)患者心房肌细胞L-型钙通道电流密度及通道电压依赖的激活和失活特性变化。方法应用两步酶解法获得单个人体心房肌细胞,采用常规全细胞膜片钳技术记录L-型钙通道电流,观察18例窦律患者和12例持续房颤患者右心房肌L-型钙通道电流密度及动力学特性变化。结果(1)持续房颤组与窦律组相比,L-型钙通道电流密度降低,测试脉冲从-40~0mV时的L-型钙通道电流密度分别为(-4.58±0.39)pA/pF(n=21)和(-1.32±0.19)pA/pF(n=12),两组比较P<0.01。(2)动力学特性:窦律组与持续房颤组比较,通道激活曲线参数半数最大激活电压(V1/2)、斜率因子(K)以及失活曲线参数半数最大失活电压(V1/2)、斜率因子(K)差异均无统计学意义。结论持续房颤患者心房肌细胞L-型钙通道电流密度明显降低,其通道动力学特性变化差异无统计学意义。L-型钙通道电流密度的变化是房颤时“心房电生理重构”离子机制之一。

Objective To investigate the changes of L-type Ca^2＋ channel current （ICa-L） and its voltage-dependent activation and inactivation in atrial myocytes of patients with atrial fibrillation （AF）. Methods The specimens of right atrial appendage were obtained from 18 patients with normal sinus rhythm （NSR） and 12 patients with chronic atrial fibrillation （CAF）. Single myocytes were isolated by enzymatic dissociation with two-step method and the ionic currents were recorded using whole-cell patch clamp techniques to detect the changes of ICa-L density and kinetic properties. Results （ 1 ） ICa-L density was （ -1.32 ±0.19） pA/pF in CAF group （n =12） and （ -4.58 ±0.39 ）pA/pF in NSR group （n =21） at the test potential from -40 mV to 0 mV. ICa-L density of CAF group was significantly reduced （P 〈0. 01 ）, compared with the NSR group. （2） No significant differences were noted between the two groups in the voltage-dependent activation parameters （ V1/2, K） and inactivation parameters （ V1/2, K）. Conclusions ICa-L density of CAF group was significantly decreased whereas it＇s vohage-dependent kinetic properties had no change. This phenomenon may be one of the mechanisms of atrial electrophysiological remodeling in chronic atrial fibrillation.