Mariko Kinoshita (1), Shuji Kaneko (2), Tohru Yasuno (1), Nobumichi Yada
(1), Akinori Akaike (1) and Masamichi Satoh (3,*)
Departments of (1) Pharmacology, (2) Neuropharmacology and (3) Molecular
Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University,
Kyoto 606-8501, Japan
(*) To whom correspondence should be addressed.
Abstract: 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.
Keywords: Bifemelane, Xenopus oocyte, N-type, Q-type, Voltage-dependent
Ca2+ channel