title: 5-HT1A receptor-mediated activation of G-protein-gated inwardly rectifying K+ current in rat periaqueductal gray neurons.
abstract: 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.
authors.affiliation: Department of Physiology, College of Medicine, Kyung Hee University, Seoul 130-701, South Korea.
authors.forename: H J
authors.initials: HJ
authors.lastname: Jeong
authors.forename: S H
authors.initials: SH
authors.lastname: Han
authors.forename: B I
authors.initials: BI
authors.lastname: Min
authors.forename: Y W
authors.initials: YW
authors.lastname: Cho
mesh_terms: D000818:Animals; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D019204:GTP-Binding Proteins / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010487:Periaqueductal Gray / Q000187:drug effects* / Q000502:physiology; D015221:Potassium Channels / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
chemical_list: D016166:Free Radical Scavengers; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D019204:GTP-Binding Proteins