SELECTIVITY OF CLASS-III ANTIARRHYTHMIC ACTION OF CLOFILIUM IN GUINEA-PIG VENTRICULAR MYOCYTES

Clofilium is an antiarrhythmic agent with a supposedly predominant cla ss-III action which is related to impairment of K+ channel function. W e investigated membrane currents in cardiac myocytes isolated from gui nea pig ventricle to evaluate the selectivity of action of clofilium o n K+ currents. For measurement of action potentials or membrane curren ts, the single electrode patch clamp technique was applied in current- or voltage-clamp mode, respectively. Clofilium (30 mu M) irreversibly prolonged the action potential duration in guinea pig myocytes. In co ntrast, the concomitant reduction in plateau phase was completely reve rsible. The delayed rectifier K+ current I-K was reduced. The rapidly activating component of I-K which has been defined by its sensitivity to the compound E-4031, was also reduced by clofilium. The inward rect ifier was slightly inhibited by the drug. Clofilium reversibly reduced L-type Ca2+ current. Sodium current was inhibited in a use-dependent manner. This effect was not reversible but proceeded after washout of the compound. Therefore, clofilium affects both inward and outward cur rents in mammalian cardiac myocytes in a similar concentration range. The effects on multiple membrane currents may contribute to the antiar rhythmic action of the drug.