抄録
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.
