Agonistic and antagonistic effect of R56865 on the Na+ channel in cardiac cells.

The effect of R56865, a benzothiazolamine derivative, on the Na+ channel was studied using different methods (indirect: Vmax measurements; direct: Na+ current under voltage clamp conditions and single channel analysis) on different cardiac preparations (rabbit Purkinje fibres, guinea-pig papillary muscles and guinea-pig ventricular single cells). Agonistic effects were obtained when hyperpolarized holding potentials and low frequency stimulation were used, antagonistic effects when depolarized holding potentials (inactivation block) and high frequency stimulation (use-dependent block) were applied. Recovery from block was voltage-dependent, and faster at hyperpolarized potentials. Burst duration was markedly shortened in DPI (DPI 201-106)-treated patches. The relation between the effects on the Na+ channel and the anti-digitalis effects are discussed.