持续性心房颤动患者心房肌细胞小电导钙激活钾通道电流的增强

Increased small conductance calcium-activated potassium channel （ SK2 channel） current in atrial myocytes of patients with persistent atrial fibrillation

目的 比较风湿性心脏病窦性心律（SR）患者和持续性心房颤动（AF）患者心房肌细胞小电导钙激活钾通道（SK2）的电流变化和通道蛋白在细胞上的分布。方法 将临床行心脏体外循环手术的患者分为SR组（15例）和AF组（7例，AF持续时间〉16个月），应用常规膜片钳全细胞记录技术记录SK2通道电流的变化，应用免疫荧光染色检测SK2在心房肌细胞上的分布。结果 在SR组和AF组心房肌细胞上均记录到内向整流钾通道混合电流，AF组电流密度明显大于SR组。在－130mV，sR组的电流密度为（－6．59±2．24）pA／pF，AF组为（－16．42±5．32）pA／pF，P〈0．01；在此基础上加入SK2特异性阻断剂apamin100nmoL／L后，使内向电流和外向电流均有所减小，内向电流减小较为明显，两者相减的为SK2电流。AF组的SK2电流明显高于SR组；在－130mV测试电压下，其电流密度分别为（－9.81±2．54）pA／pF与（－3．67±0．37）pA／pF，P〈0．01。免疫荧光染色试验证明SR组与AF组中均存在SK2通道蛋白。结论 两组心房肌细胞卜均有SK2通道蛋白的存在，AF时SK2通道电流明显增加，这表明心肌细胞上的一种新型通道SK2也参与和介导了AF的心房电重构过程。

Objective To compare the amplitude of the SK2 current （small conductance calcium- activated potassium channel ） in human atrial myicytes with or without persistent atrial fibrillation （AF）. Methods Right atrial appendage was obtained from 15 patients with sinus rate （SR） and 7 patients with AF underwent surgical valve replacement. Single myocyte was isolated by enzymatic dissociation method and the SK2 channel current density was recorded using whole-cell patch clamp techniques to detect the changes. Immunofluorescence was used to observe SK2 channel protein distribution on right atrial appendage. Results Using the whole cell patch-clamp recording techniques, an inward rectifier K^＋ mix currents could be obtained from both SR （n = 15） and AF （n =7） samples, IKl mix currents density in single myocyte of AF group was significantly increased than in SR group [ （ - 16. 42 ±5.32） pA/pF vs （ -6. 59 ±2. 24） pA/pF, P 〈0. 01 ], which could be partially inhibited by apamin （100 nmol/L）. The apamin-sensitive current was obtained by subtraction of the currents before and after treatment with apamin. SK2 current density was significantly increased in AF group than that of SR group [ （ -9.81±2. 54） pA/pF vs （ -3.67 ± O. 37） pA/pF,P 〈 0. 01 ]. SK2 channel protein was evidenced with immunofluorescence method in right atrial appendage from AF group and SR group. Conclusion SK2 channel protein and current were present in atrial myocytes. The SK2 current density was significantly increased in AF group than in SR group suggesting that the increase of SK2 current might contribute to the electrical remodeling in AF patients.