Nitrooxy Alkyl Apovincaminate Activates K^+ Currents in Rat Neocortical Neurons
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概要
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The effects of nitrooxy alkyl apovincaminate VA-045 ((+)-eburunamenine-14-carboxylic acid(2-nitroxy-ethyl ester), VA) were investigated in acutely dissociated rat neocortical neurons by using a nystatin-perforated patch recording configuration. VA activated a steady-state outward current in a concentration-dependent manner, with an EC50 of 0.65 μM. The reversal potential for the current shifted 56.5 mV with tenfold changes in the extracellular K+ concentration, suggesting that the current was carried by K+. The VA-induced current was not suppressed by apamin (1 μM), charybdotoxin (1 μM), Cs + (3 mM), Ba2+ (3 mM), 4-aminopyridine (10 mM) or glibenclamide (10 μM), whereas tetraethylammonium suppressed the current with an IC50 of 1.4 mM. These pharmacological properties of the VA-induced current were compatible with a slowly inactivating delayed rectifier current (IK). It was suggested that the current activated by VA was IK. The VA-induced current was not affected by Ca2+ depletion or by staurosporine (0.1 μM), quinacrine (10 μM), wortmanin (1 μM) or genistein (1 μM). The intracellular perfusion of GDPβS (0.4 mM) also had no significant effect. Thus, VA may directly activate the K+ channels.
- 社団法人 日本薬理学会の論文
- 2001-02-01
著者
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Araki Hiroaki
Department Of Clinical Pharmacology And Pharmacy Brain Science Ehime University Graduate School Of M
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Araki Hiroaki
大正製薬
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Araki H
Ehime Univ. Hospital Ehime Jpn
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Noguchi Kazuo
Department Of Cellular And System Physiology Graduate School Of Medical Sciences Kyushu University
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Munakata Mitsutoshi
Department Of Cellular And System Physiology Graduate School Of Medical Sciences Kyushu University
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Akaike Norio
Department Of Cellular And System Physiology Graduate School Of Medical Sciences Kyushu University
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ARAIKE Norio
Department of Cellular and System Physiology, Graduate School of Medical Sciences, Kyushu University
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