INHIBITORY EFFECTS OF BIFEMELANE ON BRAIN CA2+ CHANNEL SUBTYPES EXPRESSED IN XENOPUS OOCYTES

Effects of the cerebroprotective agent bifemelane on voltage-dependent Ca2+ channel currents were evaluated in Xenopus oocytes expressing sp ecific Ca2+-channel subtypes. Extracellular perfusion of bifemelane sh owed a dose-dependent blocking action on both N-type and Q-type Ca2+ c hannels, but not on cardiac L-type Ca2+ channels expressed in the oocy tes, and the inhibitory action on Q-type current was stronger than tha t on N-type current. The time course of inhibition by bifemelane was c omparatively slow; a 20-min perfusion with 1 mu M bifemelane was requi red to reduce the amplitude of the Q-type current to 80% of the contro l level. When bifemelane was applied intracellularly, the potency and time-course of inhibition was equivalent to that caused by the perfusi on of bifemelane. The bifemelane-induced inhibition was voltage-depend ent but not use-dependent in Q-type channels since it was apparent at more depolarized potentials but not influenced by the interval of depo larization. These results suggest that bifemelane inhibits the opening of the specific Ca2+ channels located at nerve terminals to suppress excessive neurotransmitter release from neurons in some pathophysiolog ical conditions such as ischemia.