Abstract: AIM: To explore the effect of exogenous phosphocreatine (PCr) with different concentration on L-type calcium (ICa·L) current in ischemic ventricular myocytes of guinea pig and to investigate its underlying electrophysiological mechanism for the treatment of ischemic heart failure. METHODS: Ventricular myocytes were isolated enzymatically from left ventricular of guinea pig. Peak ICa·L current were 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 min, respectively. RESULTS: Peak ICa·L current density of myocytes superfused with simple simulated ischemic solution was remarkably inhibited by (80.6±5.2)% compared with myocytes superfused with normal Tyrode solution (P<0.05). Ischemic solution containing PCr of 5, 10, 20, 30mmol/L inhibited Peak ICa·L current density by (53.8±6.7)%(P<0.05); (41.8±8.2)%(P<0.05); (38.1±7.4)%(P<0.05); (36.6±9.7)% (P<0.05), respectively. There was no statistical significance among PCr of 10, 20, 30 mmol/L. CONCLUSION: PCr could reverse the inhibition of ICa·L current under ischemic condition, which could be the ionic basis for the treatment of ischemic heart failure. 0-10 mmol/L PCr exerted a significant dose-effect relationship, which no longer existed as concentration >10 mmol/L.