Inhibitory Effects of Bifemelane on Brain Ca2+ Channel Subtypes Expressed in Xenopus Oocytes

[摘要] References(28)Cited-By(3)Effects of the cerebroprotective agent bifemelane on voltage-dependent Ca2+ channel currents were evaluated in Xenopus oocytes expressing specific Ca2+-channel subtypes. Extracellular perfusion of bifemelane showed a dose-dependent blocking action on both N-type and Q-type Ca2+ channels, but not on cardiac L-type Ca2+ channels expressed in the oocytes, and the inhibitory action on Q-type current was stronger than that on N-type current. The time course of inhibition by bifemelane was comparatively slow; a 20-min perfusion with 1 μM bifemelane was required to reduce the amplitude of the Q-type current to 80% of the control level. When bifemelane was applied intracellularly, the potency and time-course of inhibition was equivalent to that caused by the perfusion of bifemelane. The bifemelane-induced inhibition was voltage-dependent but not use-dependent in Q-type channels since it was apparent at more depolarized potentials but not influenced by the interval of depolarization. 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 pathophysiological conditions such as ischemia.

[学科分类] 药理学

[关键词] Bifemelane;Xenopus oocyte;N-type;Q-type;Voltage-dependent Ca2+ channel