Bepridil and valproate retard Na+ reactivation in Myxicola.
Two drugs were examined, each causing a similar specific modification of Na+ channel inactivation gating when internally applied to voltage-clamped Myxicola giant axons. Bepridil is an antianginal-antiarrhythmic agent with vasodilator and direct cardiac inotropic effects. Sodium valproate has anticonvulsant activity and causes use-dependent inhibition of repetitive firing in CNS neurons. Bepridil and sodium valproate caused a dose-dependent decrease in maximum Na+ conductance (KD = 25 microM for bepridil; KD = 0.5 mM for valproate). More importantly, at half-maximal blocking concentrations both drugs shifted steady state Na+ inactivation in the hyperpolarizing direction (by 30 mV for bepridil; 15 mV for valproate) and slowed the recovery of Na+ channels from inactivation (by 300% for bepridil; 60% for valproate). There was no effect on the K+ conductance, voltage-dependence of Na+ activation, or the time-dependence of inactivation of conducting channels. Neither produced non-inactivating Na+ current during long depolarizing steps.
D000818:Animals; D001369:Axons / Q000187:drug effects*; D015764:Bepridil; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D066298:In Vitro Techniques; D011077:Polychaeta / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism*; D014635:Valproic Acid / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D011759:Pyrrolidines; D014635:Valproic Acid; D015764:Bepridil; D012964:Sodium; D011188:Potassium