5-HT1A receptor-mediated activation of G-protein-gated inwardly rectifying K+ current in rat periaqueductal gray neurons.

5-hydroxytryptamine (5-HT) has been reported to modulate analgesia produced by opioids or electrical stimulation of the periaqueductal gray (PAG). 5-HT increases K+ conductance and inhibits the firing activity of the PAG neurons. We examined the electrophysiological and pharmacological characteristics of the K+ current involved in 5-HT-induced hyperpolarization of dissociated rat PAG neurons. Among the neurons tested, 5-HT activated inward K+ currents in 30-40%, whilst the remaining 60-70% did not respond to 5-HT. 5-HT activated an inwardly rectifying K+ current (I5-HT) in a concentration- and voltage-dependent manner. I5-HT was mimicked by a 5-HT1A receptor selective agonist, 8-OH-DPAT, and was reversibly blocked by a 5-HT1A receptor antagonist, piperazine maleate, but not by a 5-HT2 receptor antagonist, ketanserin. I5-HT was sensitive to K+ channel blockers such as quinine and Ba2+, but insensitive to 4-aminopyridine, Cs+ and tetraethylammonium. I5-HT was inhibited by GDP(beta)s and was irreversibly activated by GTP(gamma)s. I5-HT was significantly suppressed by N-ethylmaleimide and pertussis toxin, but not by cholera toxin. Second messenger modulators such as staurosporin, forskolin, and phorbol-12-myristate-13-acetate did not alter I5-HT. The present study indicates that 5-HT-induced hyperpolarization of the PAG neurons results from activation of the pertussis toxin-sensitive G-protein-coupled inwardly rectifying K+ currents through 5-HT1A receptors.