蛋白激酶C对心房颤动患者心房肌小电导钙激活钾通道的影响

Protein kinase C regulates SK2 channels in human atrial fibrillation

目的:比较心房颤动(AF)时蛋白激酶C(PKC)对小电导钙激活钾通道(SK)电流的影响,探讨人AF时PKC途径对SK2通道的调节作用。方法:取行体外循环手术患者新鲜的右心耳组织,采用改良的酶分离法获得单个心房肌细胞,全细胞膜片钳模式且电极液中游离钙离子浓度为5×10-7 mol/L时记录SK2通道电流。比较正常的窦性心律组(SR组)和AF组患者心房肌细胞SK2通道电流密度,观察PKC特异性激活剂PMA对SK2通道电流的影响。结果:1AF组SK2通道电流密度明显大于SR组,且AF组SK2通道电流在混合内向电流中所占的比例明显增加;在-130mV膜电压下,SR组和AF组SK2通道电流密度分别(-5.10±0.32)pA/pF(nSR=5)和(-10.71±0.73)pA/pF(nAF=5),P<0.05;SR组和AF组SK2通道电流在混合内向电流中所占的比例分别为(23.20±1.09)%和(32.87±1.81)%(nSR=5,nAF=6),P<0.05。2PKC激活剂PMA降低SR组和AF组SK2通道电流密度及其在混合电流中所占的比例,AF组的抑制比大于SR组;在-130mV电压下,PMA对SK2通道电流的抑制比分别为(8.39±0.80)%和(20.9±0.70)%。结论:AF时SK2通道功能增强,激活PKC后可下调SK2通道电流,且对AF患者SK2的调节作用更显著,推测PKC相关途径对SK2通道的调控参与了心房电重构过程。

Objective：To investigate protein kinase C（PKC）regulates small-conductance Ca^2＋-activated K＋（SK）channels in human patients with atrial fibrillation（AF）.Method：The regulation of SK2 channels by PKC were detected in isolated human atrial cardiomyocytes with whole-cell patch clamp experiments between SR and AF group.The currents were recorded when the concentration of free[Ca^2＋]in the internal solution was 5×10^-7mol/L.Result：The SK2 channel current density（pA/pF）as well as the ratio in the integrated inward currents was significantly up-regulated in AF group.PMA reduced the inhibition ratio of SK2 channel in the integrated inward currents in both SR and AF group.Inhibition ratio with SR group was larger than that in AF group.Conclusion：SK2channel up-regulated in AF.Activation of PKC can down-regulate SK2 channel,which has more significant role in the AF patients.PKC-dependent regulation may be involved in atrial electrical remodeling process.