5-HT1A receptor-mediated activation of a G-protein-coupled inwardly rectifying K+ current in rat medial preoptic area neurons.
The medial preoptic area plays an important role in the regulation of sexual behavior, and serotonin (5-hydroxytryptamine, 5-HT) exerts an inhibitory effect on sexual behavior by acting on the medial preoptic area region. This study was designed to clarify the inhibitory effect of 5-HT on the medial preoptic area neurons and to elucidate the electrophysiological mechanisms involved in the action of 5-HT. Superfusion of 100 nM 5-HT hyperpolarized the membrane potential and inhibited the action potential firing. When the membrane potential was stepped to various potentials, the inward K+ currents were potentiated in the presence of 100 nM 5-HT. When the concentration of K+ in the external solution was increased from 5 mM to 30 mM, 5-HT markedly potentiated the inward K+ currents. In the steady-state current-voltage relationship, the 5-HT-activated inward current was carried by K+ ions and showed characteristics typical of an inwardly rectifying K+ current. The 5-HT-activated K+ current was mimicked by a 5-HT1A receptor agonist, (+/-)-8-hydroxy-2-dipropylaminotetralin hydrobromide, and was reversibly blocked by a 5-HT1A receptor antagonist, 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl] piperazine hydrobromide, but not by a 5-HT2 receptor antagonist, ketanserin. The 5-HT-activated K+ current was sensitively blocked by Ba2+, but not by 4-aminopyridine, and was completely suppressed by N-ethylmaleimide. These results indicate that 5-HT-induced hyperpolarization of the medial preoptic area neurons occurs as a result of activation of the G-protein-coupled inwardly rectifying K+ currents by 5-HT1A receptors.
Lee
Jong-Ju
JJ
Department of Physiology, Biomedical Science Institute, Kyung Hee University School of Medicine, Seoul 130-701, South Korea.
Hahm
Eu-Teum
ET
Lee
Choong-Hyun
CH
Cho
Young-Wuk
YW
D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009761:Nystatin / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011301:Preoptic Area / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D007476:Ionophores; D026902:Potassium Channel Blockers; D012702:Serotonin Antagonists; D044282:Receptor, Serotonin, 5-HT1A; D009761:Nystatin; D012701:Serotonin; D005033:Ethylmaleimide