Jpn. J. Pharmacol. 85 (2), 124-132 (2001)

Nitrooxy Alkyl Apovincaminate Activates K+ Currents in Rat Neocortical Neurons

Mitsutoshi Munakata1, Kazuo Noguchi1,2,*, Hiroaki Araki3 and Norio Akaike1

1Department of Cellular and System Physiology, Graduate School of Medical Sciences, Kyushu University, 1-2-2 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
2Pharmacology Laboratory, Pharmaceutical Research Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Ohmiya, Saitama 330-8530, Japan
3Department of Hospital Pharmacy, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558, Japan
*Corresponding author (affiliation #2). FAX: +81-48-654-6650

Abstract: 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 mM. 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 mM), charybdotoxin (1 mM), Cs + (3 mM), Ba2+ (3 mM), 4-aminopyridine (10 mM) or glibenclamide (10 mM), 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 mM), quinacrine (10 mM), wortmanin (1 mM) or genistein (1 mM). The intracellular perfusion of GDPbS (0.4 mM) also had no significant effect. Thus, VA may directly activate the K+ channels.

Keywords: VA-045, Nitrooxy alkyl apovincaminate, K+ channel, Delayed rectifier, Neocortical neuron (rat)

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