Bepridil block of cardiac calcium and sodium channels.
The effects of bepridil, a new Ca channel blocking agent with reported antiarrhythmic action, were examined in single isolated ventricular cells using whole-cell patch clamp techniques. Ca currents were studied in guinea-pig ventricular cells and Na currents were studied in cultured ventricular cells from neonatal rat, a preparation which is more suitable for Na current measurements than guinea pig. At low frequencies (0.1 Hz) and negative holding potentials (-50 mV for Ca currents and -100 mV for Na currents), bepridil produced a concentration-dependent decrease in both Ca and Na currents without any significant change in the current-voltage relations. Concentration-response curves for block of Ca and Na channels were fitted by a one-to-one drug-receptor occupancy model. Half-blocking concentrations (IC50) of bepridil were 5 x 10(-7) M for Ca currents and 3 X 10(-5) M for Na currents. Bepridil had no effect on the inwardly rectifying K current and the time-dependent outward current. The effects of bepridil on Ca and Na currents depend upon the holding potential. Inactivation curves of the Ca and Na currents were shifted to more negative potentials by the drug. The recovery of both the Ca and Na currents from inactivation was always prolonged by bepridil and the repriming of both currents usually displayed an added exponential component, attributed to slow release of the drug from the channels. The results indicate that bepridil, by inhibiting both Ca and Na currents, may have clinical usefulness in the treatment of certain ischemia-induced ventricular arrhythmias.
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Yatani
A M
AM
Brown
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Schwartz
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D015764:Bepridil; D002121:Calcium Channel Blockers; D004553:Electric Conductivity; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D008564:Membrane Potentials; D011759:Pyrrolidines / Q000494:pharmacology*; D012964:Sodium / Q000037:antagonists & inhibitors*
D002121:Calcium Channel Blockers; D007473:Ion Channels; D011759:Pyrrolidines; D015764:Bepridil; D012964:Sodium