摘要
目的 研究普罗帕酮对钾通道亚型Kv4 2和Kv4 3电流的影响。方法 采用全细胞膜片钳技术记录稳定表达Kv4 2和Kv4 3电流的人胚胎肾细胞株 (HEK2 93细胞 )电流的变化。结果 ①普罗帕酮明显抑制Kv4 2和Kv4 3电流 ,呈浓度依赖性 ,IC50 分别为 1 0 3 μmol·L- 1 和 71 μmol·L- 1 ;②普罗帕酮明显加速Kv4 2和Kv4 3电流失活 ,1 0μmol·L- 1 的普罗帕酮可使Kv4 2电流衰减时间常数τ由(38 9± 2 1 )ms变为 (9 9± 1 8)ms ,半数最大失活膜电位V1 /2 由 (- 66 6± 0 8)mV左移至 (- 70 9± 1 1 )mV ;1 0 0μmol·L- 1 的普罗帕酮可使Kv4 3电流衰减时间常数τ(1 4 4 8± 2 0 8)ms变为 (1 8 5± 2 8)ms,半数最大失活膜电位V1 /2 由 (- 4 5 6± 1 9)mV左移至 (- 52 3± 2 1 )mV ;③普罗帕酮明显左移Kv4 2和Kv4 3电流的激活曲线 ,1 0μmol·L- 1 的普罗帕酮可使Kv4 2电流半数最大激活膜电位V1 /2 由 (- 4 1± 0 5)mV左移至 (- 1 6 1± 2 4)mV ;1 0 0μmol·L- 1 的普罗帕酮可使Kv4 3半数最大激活膜电位V1 /2由 (- 6 0± 1 1 )mV左移至 (- 1 6 5± 3 0 )mV。结论 普罗帕酮明显抑制Kv4 2 ,Kv4 3电流 ,该作用可能是其治疗心律失常的机制之一。
AIM To study the effects of propafenone on Kv 4 2 and Kv4 3 potassium current. METHODS Whole cell patch clamp technique was used to record changes of Kv4 2 and Kv4 3 potassium currents. RESULTS ① Propafenone redu ced the amplitude of Kv4 2 and Kv4 3 currents, in a concentration-dependent, IC 50 was 10 3 and 71 μmol·L -1 respectively. ② Propafenone inhibi ted Kv4 2 and Kv4 3 current inactivation, 10 μmol·L -1 propafenone acce lerates Kv4 2 current inactivation constant from (38 9±2 1) ms to (9 9±1 8) ms; and shifted the steady state inactivation curves of Kv4 2 current to negative potentials. 100 μmol·L -1 Propaf enone accelerates Kv4 3 current inactivation constant from (144 8±20 8) ms t o (18 5±2 8) ms; and shifted the steady state inactivation curves of Kv4 2 c urrent to negative potentials. ③ propafenone inhibited Kv4 2 and Kv4 3 curren t activation, 10 μmol·L -1 propafenone shifted the steady state activati on curves of Kv4 2 current to negative potentials. 100 μmol·L -1 propafe none shifted the steady state activation curves of Kv4 2 current to negative po tentials. CONCLUSION Propafenone, maybe, also exerts its effects via blocking Kv4 2 and Kv4 3 current to antiarrhythmia.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2003年第8期867-871,共5页
Chinese Pharmacological Bulletin
基金
国家"8 6 3"重大基础项目研究计划资助课题 (No 2 0 0 1AA2 34 0 2 1)
国家"973"重大基础项目研究计划资助课题 (NoG19980 5110 6 )
