外源性磷酸肌酸对缺血豚鼠心室肌细胞钠通道的影响Δ

Effect of exogenous phosphocreatine on natrium current in ischemic ventricular myocytes of guinea pig

关键词:  膜片钳  钠电流  缺血  磷酸肌酸  豚鼠

Key words:  Patch clamp  Natrium current  Ischemia  Phosphocreatine  Guinea pig

摘要:

目的：观察不同浓度外源性磷酸肌酸(exogenous phosphocreatine, PCr)对豚鼠缺血心室肌细胞钠通道(I_Na)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：心室肌细胞经酶解从豚鼠左心室获得,膜片钳全细胞模式记录I_Na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5, 10, 20,30 mmol/L浓度。将细胞分成6组,分别予模拟缺血液,含有5, 10, 20,30mmol/L浓度PCr的模拟缺血液,台氏液灌流,后者充以95%O₂ 5%CO₂的混合气体。10min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I_Na峰电流密度降低80.1?2.5%(p<0.05),含有5, 10, 20, 30mmol/L浓度PCr的模拟缺血液组I_Na峰电流密度分别降低56.2?4.6%(p<0.05)；30.3?5.3%(p<0.05)；39.0?5.5%(p<0.05)；42.6?4.8%(p<0.05)。10与5, 20, 30mmol/L之间具有统计学差异(p<0.05)。结论： PCr能增加缺血时受抑制的I_Na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。PCr在低浓度 (0~10mmol/L)对I_Na峰电流及电流密度的影响呈现明显的量效关系。

Abstract:

Objective: The aim of this study is to determine the effect of exogenous phosphocreatine(PCr) with different concentration on natrium ( I_Na ) current in guinea pig ischemic ventricular myocytes and to explore the antiarrhythmia mechanism in the treatment of ischemic heart disease. Methods: Ventricular myocytes were isolated enzymatically from left ventricular of guinea pig. Peak I_Nacurrent was recorded using patch clamp techniques in the whole-cell configuration when myocytes had been superfused with normal Tyrode solution, simple ischemic solution, ischemic solution containing PCr with different concentration of 5, 10, 20, 30 mmol/L for 10 minutes respectively. Results: Peak I_Na current density of myocytes superfused with simple simulated ischemic solution was significantly reduced by 80.1?2.5%(p<0.05)compared with myocytes superfused with normal Tyrode solution. Ischemic solution containing PCr of 5, 10, 20, 30mmol/L reduced peak I_Na current density by 56.2?4.6%(p<0.05)；30.3?5.3%(p<0.05)；39.0?5.5%(p<0.05)；42.6?4.8%(p<0.05)respectively. There was Statistical significance among ischemic solution containing PCr of 10 and 5, 20, 30 mmol/L(p<0.05)。Conclusion: PCr could reverse the inhibition of I_Nacurrent under ischemic condition, which could be the mechanism responsible for arrhythmia prevention in ischemia heart disease. 0~10mmol/L PCr exerted significant dose-effect relationship and concentration more than 10mmol/L could slightly decrease I_Na current density.