5-HT 1A receptor-mediated activation of a G-protein-coupled inwardly rectifying K + current in rat medial preoptic area neurons

Abstract

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-HT 1A receptor agonist, (±)-8-hydroxy-2-dipropylaminotetralin hydrobromide, and was reversibly blocked by a 5-HT 1A receptor antagonist, 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl] piperazine hydrobromide, but not by a 5-HT 2 receptor antagonist, ketanserin. The 5-HT-activated K + current was sensitively blocked by Ba 2+, 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-HT 1A receptors.