Diphenylamine-2-carboxylate (DPC) is a known and widely used blocker of chloride channels. In the present study, the effect of DPC on fast Na+ channels and slow L-type Ca2+ channels in freshly isolated rat ventricular myocytes was investigated. Currents were recorded (at 25 degrees C) in whole-cell voltage-clamp. The fast Na+ current (INa(f)) was recorded in Ca(2+)-, K(+)-free solutions (external and pipette), with depolarizing pulses applied from -80 mV to -20 mV. The L-type Ca2+ current (ICa(L)) was recorded in Na(+)-, K(+)-free (external) and Ca(2+)-, K(+)-free (pipette) solutions, with depolarizing steps applied from -40 mV (holding potential) to +10 mV. Perfusion with different concentrations of DPC (from 0.01 to 10 mM) blocked the INa(f) and ICa(L) currents in a dose-dependent manner. The concentrations of DPC producing half-maximum inhibition (IC50) were 0.18 mM and 0.47 mM, respectively, for INa(f) and ICa(L). The effect of DPC on INa(f) occurred rapidly, namely within 1 min after addition of the drug and was completed within 3 min. The effect of DPC on ICa(L) had a similar time-course, the maximal steady-state effect being reached by 4-7 min. The effect of DPC was rapidly and completely reversible upon washout. In conclusion, DPC inhibits Na+ and Ca2+ currents in rat ventricular cardiomyocytes, and is equally potent, or even more potent, than that reported for Cl- channels or other DPC-sensitive channels.