Journal de pharmacocinétique et thérapeutique expérimentale

Abstrait

Effect of Exogenous Phosphocreatine on Ito, Ina And Ica,L in IschemicVentricular Myocytes of Rat

Shi Xiang-Min, Li Tian-De, Wang Yu-Tang, Yang Ting-Shu and Shan Zhao-Liang

Aim: The aim of this study is to determine the effect of exogenous phosphocreatine (PCr) with different concentration on transient outward potassium (Ito), natrium (INa) and L-type calcium (ICa,L) current in ischemic ventricular cells of rat and to explore its role in the treatment of ischemic heart disease. Methods: Ventricular cells were isolated enzymatically from left ventricular of rat. Peak Ito, INa and ICa,L current were recorded using patch clamp techniques in the whole-cell configuration in the setting of cells super fused with normal Tyrode solution, simple simulated ischemic solution (SI), ischemic solution containing PCr with concentration of 5, 10, 20, 30 mmol/L for 10 min respectively. Results: Compared with simple simulated ischemic solution, peak Ito, INa and ICa,L current and current density of ischemic solution containing PCr of 5, 10, 20, 30 mmol/L significantly improved (p<0.05). There were statistical significance among PCr of 10 and 0, 5 mmol/L for Ito, INa and ICa,L, no significant difference were found among10, 20 and 30 mmol/L for Ito and ICa,L (p>0.05). Compared with PCr of 10 mmol/L, peak INa current and density decreased in that of 20 and 30 mmol/L (p<0.05). Conclusion: PCr could partly reverse the inhibition of Ito, INa and ICa,L current of rat ventricular cells under ischemic condition, which could be the ionic basis of therapeutic role in the treatment of ischemic heart disease. 0 ~ 10 mmol/L PCr exerted significant dose-effect relationship.