We investigated eiTects of a novel cardioprotective drug, J TV—519 (4—[3-(4-benzylpiperidin-1-yl) propiony1]-7-methoxy—2, 3, 4, 5-tetrahydro-1, 4—benzothiazepine monohydrochloride) on membrane currents of guinea pig ventricular myocytes by whole—cell voltage and current clamp methods. The fast NaJr current (iNa) was activated by ramp pulses from various holding potentials of—90,—80 or——60 mV to 10 mV with various intervals. At 0.2 Hz, J TV-519 inhibited iNa in a concentration-dependent manner with an IC50 of approximately 1.2 and 2 pM at the holding potential of—60 and—90 mM, respectively, implicating a voltage-dependent block. Increasing the pulse frequency from 1 to 2 or 3.3 Hz in the presence of 1 pM J TV-519 shortened the time-course and increased the level of iNa block, indicating a frequency-dependent block. The time-course of iNa blocking by JTV-519 was slower than that of lidocaine and similar to that of quinidine. Ca2+ current 001) and the inwardly rectifying KJr current (iKl) were also inhibited by J TV-519. JTV—519 decreased the duration and the height of the plateau of the action potential. We conclude that J TV-519 has frequency—and voltage-dependent blocking effects on iNa as well as inhibition of ica and in.