The effects of propyl paraben, an antimicrobial preservative, on voltage-dependent sodium current and myocardial ischemia-reperfusion injury were investigated in isolated adult rat cardiomyocytes. Whole cell voltage-clamp recording showed that propyl paraben reversibly blocked the voltage-gated sodium channel both in concentration- and voltage-dependent manners. Propyl paraben (500 microM but not 100 microM) significantly shifted the steady-state inactivation of the sodium channel toward the hyperpolarizing direction at the V(1/2) point. Consistent with the above result, the propidium iodide (PI) uptake test revealed that pretreatment with 500 microM but not 100 microM of propyl paraben significantly reduced cell death induced by 45 min of sustained ischemia followed by 15 h of reperfusion (42.37 +/- 7.01% of cell viability in control and 71.05 +/- 7.06% in the propyl paraben group), suggesting that propyl paraben can protect myocytes from ischemia-reperfusion injury. These results indicate a possible correlation between the inhibition of sodium current and cardioprotection against ischemia-reperfusion injury.