BLOCK OF NA-PIG VENTRICULAR MYOCYTES( CHANNEL BY BEPRIDIL IN ISOLATEDGUINEA)

The effects of bepridil, a potent antiarrhythmic agent, on the Na+ cur rent (I-Na) of single guinea-pig ventricular myocytes were studied usi ng the whole-cell patch-clamp technique. Bepridil inhibited I-Na in a dose-dependent manner without causing any change in the I-V relationsh ip for I-Na. Bepridil suppressed I-Na with K-d values of 342 and 40 mu M when cells were clamped to holding potentials of -140 and -90 mV, r espectively. 10 mu M bepridil shifted the steady-state inactivation cu rve for I-Na toward more negative potentials by 7.7 mV (n = 6). Beprid il also produced marked use-dependent block with a rapid onset. Recove ry of I-Na from inactivation was retarded (time constant 290 ms) at a holding potential of -140 mV in the presence of 10 mu M bepridil. When the onset of I-Na block was studied in experiments using a double-pul se protocol, bepridil blocked I-Na by 11.5% after a 4-ms pre-pulse, bu t significantly blocked it after pre-pulses longer than 16 ms. These r esults suggest that: (1) bepridil has a higher affinity for the inacti vated state than the resting state of Na+ channel; (2) the drug also p roduces an open channel block; and (3) the drug shows a lidocaine-like fast kinetic block of Na+ current.