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 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 microM 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.
Kinoshita
M
M
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan.
Kaneko
S
S
Yasuno
T
T
Yada
N
N
Akaike
A
A
Satoh
M
M
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D015220:Calcium Channels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008564:Membrane Potentials / Q000187:drug effects; D009865:Oocytes / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D013997:Time Factors; D014981:Xenopus
D000928:Antidepressive Agents; D001559:Benzhydryl Compounds; D015220:Calcium Channels; C031906:bifemelane