缬沙坦对豚鼠心房肌细胞电生理的影响

Effects of valsartan on electrophysiology of guinea pig atrial myocytes

目的从心肌细胞电生理的角度探讨血管紧张素Ⅱ受体阻断药（ARB）类药物抗房颤的可能机制。方法采用全细胞膜片钳技术的电流钳方法记录单细胞动作电位，采用全细胞膜片钳技术的电压钳方法记录心房肌细胞的延迟整流钾电流（Ik）。观察ARB类药物缬沙坦对豚鼠心房肌细胞动作电位及离子通道电流的影响。结果缬沙坦100μM可延长心房肌细胞动作电位时程，尤其是蛾从（52．2±6．5）ms延长至（58．6±7．8ms，P〈0．01），APD90从（94．0±11．7）ms延长至（105．3±14．0ms，P〈0．01），而对RMP、APA无显著影响。缬沙坦100μM明显抑制心房肌细胞IK的峰值电流，从5．33±0．13（pA／pF）减小至4．49±0．48（pA／pF）（P〈0．05），并呈电压依赖性。结论高浓度缬沙坦延长心房肌细胞动作电位时程、APD50及APD50。缬沙坦抑制心房肌细胞延迟外向钾电流，可能是引起其动作电位时程延长的一个重要因素。缬沙坦延长心房肌动作电位时程，可能在房颤的转复及房颤转复后窦性心律的维持中有价值。

Objective To study the potential mechanism of angiotensin Ⅱ blocker（ARB）on atrial fibrillation from cellular electrophysiology of myocytes. Methods Whole - cell patch clamp technique was adopted. Current- clamp mode was used to record single cell action potential. The effect of ARB on action potential of guinea pig atrial myocytes were investigated. Patch - clamp mode was used to record delayed rectifier K^＋ currents （Ik）. Results V alsartan 100 μM lengthened atrial myocyte action potential duration, especially APD50 from （52.2 ±6.5） ms to （58.6±7.8） ms（ P 〈0.01）and APDgO from （94.0± 11.7） ms to （105.3 ± 14.0） ms（ P 〈 0.01） ,but had no effect on RMP and APA. Valsartan 100 μm reduced atrial myocytes peak Ik current from 5.33 ± 0.13（ pA/pF） to 4.49 ± 0.48（pA/pF） ,voltage dependently. Conclusions At high concentration, valsaxtan increases APD of atrial myocytes of guinea pig without changing APA and RMP. Inhibiting Ik by valsartan is an important factor contributing to the prolongation of APD. By prolonging APD, valsartan may have potential in converting AF to sinus rhythm or in maintaining sinus rhythm after successful convertion.