Nitrooxy Alkyl Apovincaminate Activates K+ Currents in Rat Neocortical Neurons

The Japanese Journal of Pharmacology

Norio Akaike²  Kazuo Noguchi²  Hiroaki Araki¹  Mitsutoshi Munakata² 

[1] Department of Hospital Pharmacy, Okayama University Medical School;Department of Cellular and System Physiology, Graduate School of Medical Sciences, Kyushu University

关键词: VA-045;    Nitrooxy alkyl apovincaminate;    K+ channel;    Delayed rectifier;    Neocortical neuron (rat);   

DOI  :  10.1254/jjp.85.124

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(24)Cited-By(2)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.

【 授权许可】

Unknown