替米沙坦对电压依赖性的Kv1.3和Kv1.5通道电流阻断作用的实验研究

目的 通过观察替米沙坦对电压依赖性的Kv1.3和Kv1.5的阻断作用,探讨替米沙坦对此类通道的阻断可能具有的临床作用.方法 使用双电极电压钳技术记录表达于非洲爪蟾卵母细胞的Kv1.3和Kv1.5钾通道电流,不同浓度灌流观察其对电流影响.结果 (1)替米沙坦浓度依赖性的阻断Kv1.3通道,其阻断的IC50是2.05 μmol/L.替米沙坦对Kv1.3电流的阻断具有电压依赖性.(2)替米沙坦浓度依赖件的阻断Kv1.5通道,其阻断的IC50是2.37 μmol/L.替米沙坦对Kv1.5电流的阻断具有更显著的电压依赖性.结论 替米沙坦阻断开放状态的Kv1.3可能是其发挥免疫调节和抗动脉粥样硬化作用的机制之一.替米沙坦对开放状态的Kv1.5钾通道的阻断可能是其减少心房颤动发生率的作用机制之一.

Effects of telmisartan on voltage-gated Kv1.3 and Kv1.5 potassium channels expressed in Xenopus oocytes

Objective To observe the effects of telmisartan on Kv1.3 and Kv1.5 potassium channels expressed in Xenopus oocytes. Methods Kv1.3 and Kv1.5 potassium channel currents expressed in Xenopus oocytes were recorded and observed in the absence and presence of telmisartan using standard two-microelectrode voltage clamp techniques. Results Telmisartan resulted in a concentration- and voltage-dependent inhibition effect on Kv1.3 channel current (IC50 2.05 μmol/L) and on Kv1. 5 channel current (IC50 2.37 μmol/L). Conclusions Telmisartan blocks open-state Kv1.3 channel which could be one of the mechanisms related to its immunomodulatory and anti-atherosclerosis effect. Telmisartan also blocks open-state Kv1.5 channel which might partly account for its effect on reducing the incidence of atrial fibrillation.