摘要
许多研究证实三磷酸腺苷敏感性钾电流 (KATP)在心肌保护的机制中起重要作用 ,但尚未有缺血预适应 (IPC)期间KATP电流变化的直接报道。本实验用全细胞膜片钳技术在豚鼠心室肌细胞上观察了多次模拟缺血 (低氧、去能量 )和再灌注期间KATP电流的变化情况。结果 :对照组 (n =9)和IPC组 (n =12 )的KATP电流分别由实验开始时的- 97± 14和 - 94± 16pA开放至第 3次短暂缺血结束时的 - 5 7± 10和 - 16± 2 0pA(P <0 .0 5 ) ,以及持续缺血 5min时的 35± 2 3和 472± 310pA(P均 <0 .0 1) ;然而在持续缺血晚期和再灌注过程中KATP通道的开放程度在两组之间无显著差异。以上这些效应可被优降糖阻断。结论 :本文首次直接观察到IPC可导致KATP通道在预适应末及随后长时间缺血早期的适度激活 ,但不影响长时间缺血晚期和再灌注过程中的开放程度 。
Adenosine triphosphate sensitive K + channels (K ATP ) have been shown by numerous investigators to play an essential role in the mechanisms of cardioprotection.Thus far,however,the direct recordings of K ATP current during ischemic preconditioning (IPC) have never been reported.The whole cell patch clamp recording technique was used to directly investigate the K ATP current alterations during simulated ischemia (hypoxia,glucose free) and reperfusion in isolated guinea pig ventricular myocytes.Three groups were divided into:1) Baseline (BL):18 min normal solution perfusion; 2) IPC:3 cycles of IPC (3 min ischemia+3 min reperfusion);3) Glb:exposure to glibenclamide (1 μM/L) during 3 cycles of IPC.Then 15 min sustained ischemia and 5 min reperfusion were conducted in all three groups.The K ATP currents of IPC group were significantly increased after cycle 3 of IPC compared with BL group ( P <0.05).The increased K ATP currents also occurred 3～7 min after subsequent sustained ischemia,among which the most significant K ATP difference between two groups occurred at 5 min after sustained ischemia ( P <0.01).However,the opening extent of K ATP channel during late stage of subsequent sustained ischemia and reperfusion were similar between BL and IPC groups.These effects could be blocked by Glb.Conclusion:These results first directly demonstrated that K ATP is activated in IPC procedure,mainly through its opening during IPC period and early stage of subsequent sustained ischemia,but not during the late stage of sustained ischemia period and reperfusion.The mechanisms need to be further explored.
出处
《中国心脏起搏与心电生理杂志》
2001年第4期269-272,共4页
Chinese Journal of Cardiac Pacing and Electrophysiology
基金
北京市科技新星计划资助 (合同号 95 5 810 10 0 0 )
关键词
心肌缺血
预适应
三磷酸腺苷敏感性钾通道电流
全细胞膜片钳技术
Ischemic preconditioning ATP Sensitive potassium current Whole cell patch clamp technique Ventricular myocytes Glibenclamide Guinea pig
