磷酸肌酸对缺血大鼠心室中层心肌细胞瞬间外向钾电流的影响(英文)

Effect of phosphocreatine on transient outward potassium current in ischemic ventricular mid-myocardial cells of rats

目的:观察不同浓度外源性磷酸肌酸(phosphocreatine,PCr)对大鼠缺血心室中层心肌细胞(M细胞)瞬间外向钾通道(Ito)电流的影响,探讨其预防缺血性心律失常的电生理学机制。方法:单个M细胞经酶解从大鼠左心室中层获得,采用膜片钳全细胞模式记录Ito电流,通过灌注模拟缺血液并充以95%N2+5%CO2的混合气体建立缺血模型,将PCr加入模拟缺血液中分别配成终浓度5、10、20和30 mmol/L。将细胞分成6组,分别给予模拟缺血液,含有5、10、20和30 mmol/L PCr的模拟缺血液以及台氏液灌流,后者充以95%O2+5%CO2的混合气体。10 min后记录各组的峰电流及电流密度。结果:与台氏液组相比,单纯模拟缺血液组Ito峰电流密度降低(76.1±6.3)%(P<0.05),含有5、10、20和30 mmol/L PCr的模拟缺血液组Ito峰电流密度分别降低(57.1±9.6)%(P<0.05)、(40.3±10.3)%(P<0.05)、(34.3±9.6)%(P<0.05)和(32.1±10.6)%(P<0.05)。PCr为0、5、10 mmol/L时三者峰电流密度具有明显差异(P<0.05)。PCr为10、20、30 mmol/L对Ito峰电流密度的影响无显著差异(P>0.05)。结论:PCr能增加缺血时受抑制的M细胞Ito峰电流及电流密度,这可能是其预防缺血性心律失常的电生理学机制。低浓度(0～10 mmol/L)PCr对Ito峰电流及电流密度的影响呈现明显的量效关系。

AIM： To determine the effect of exogenous phosphocreatine（PCr） at different concentrations on transient outward potassium（Ito） current in rat ischemic ventricular mid-myocardial（M） cells and to explore the antiarrhythmia mechanism in the treatment of ischemic heart disease.METHODS： M cells were isolated enzymatically from left ventricular mid-myocardium of rats.Peak Ito current was recorded by patch-clamp technique in the whole-cell configuration when M cells were superfused with normal Tyrode solution,simple ischemic solution,and simulated ischemic solution containing PCr at concentrations of 5,10,20 and 30 mmol/L for 10 min.RESULTS： Peak Ito current density of M cells superfused with simple simulated ischemic solution was significantly reduced by（76.1±6.3）%（P0.05） compared with M cells superfused with Tyrode solution.Ischemic solution containing 5,10,20 and 30 mmol/L PCr reduced peak Ito current density by（57.1±9.6）%（P0.05）,（40.3±10.3）%（P0.05）,（34.3±9.6）%（P0.05） and（32.1±10.6）%（P0.05）,respectively.There was statistical difference among ischemic solution without PCr and containing PCr at concentrations of 5 and 10 mmol/L groups（P0.05）.No statistical difference among groups of 10,20 and 30 mmol/L PCr was observed（P0.05）.CONCLUSION： PCr reverses the inhibition of Ito current under ischemic condition in M cells,which may be the mechanism responsible for arrhythmia prevention in ischemic heart disease.PCr at concentrations of 0～10 mmol/L exerts significant dose-effect relationship.