title: Serotonin 5-HT1B receptor-mediated calcium influx-independent presynaptic inhibition of GABA release onto rat basal forebrain cholinergic neurons.
abstract: Modulatory roles of serotonin (5-HT) in GABAergic transmission onto basal forebrain cholinergic neurons were investigated, using whole-cell patch-clamp technique in the rat brain slices. GABAA receptor-mediated inhibitory postsynaptic currents (IPSCs) were evoked by focal stimulation. Bath application of 5-HT (0.1-300 μm) reversibly suppressed the amplitude of evoked IPSCs in a concentration-dependent manner. Application of a 5-HT1B receptor agonist, CP93129, also suppressed the evoked IPSCs, whereas a 5-HT1A receptor agonist, 8-OH-DPAT had little effect on the evoked IPSCs amplitude. In the presence of NAS-181, a 5-HT1B receptor antagonist, 5-HT-induced suppression of evoked IPSCs was antagonised, whereas NAN-190, a 5-HT1A receptor antagonist did not antagonise the 5-HT-induced suppression of evoked IPSCs. Bath application of 5-HT reduced the frequency of spontaneous miniature IPSCs without changing their amplitude distribution. The effect of 5-HT on miniature IPSCs remained unchanged when extracellular Ca(2+) was replaced by Mg(2+) . The paired-pulse ratio was increased by CP93129. In the presence of ω-CgTX, the N-type Ca(2+) channel blocker, ω-Aga-TK, the P/Q-type Ca(2+) channel blocker, or SNX-482, the R-type Ca(2+) channel blocker, 5-HT could still inhibit the evoked IPSCs. 4-AP, a K(+) channel blocker, enhanced the evoked IPSCs, and CP93129 had no longer inhibitory effect in the presence of 4-AP. CP93129 increased the number of action potentials elicited by depolarising current pulses. These results suggest that activation of presynaptic 5-HT1B receptors on the terminals of GABAergic afferents to basal forebrain cholinergic neurons inhibits GABA release in Ca(2+) influx-independent manner by modulation of K(+) channels, leading to enhancement of neuronal activities.
authors.affiliation: Department of Pharmacology, Jikei University School of Medicine, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Nishijo
authors.affiliation: Department of Pharmacology, Jikei University School of Medicine, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Momiyama
mesh_terms: D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D059329:Cholinergic Neurons / Q000378:metabolism* / Q000502:physiology; D005089:Exocytosis; D053444:Inhibitory Postsynaptic Potentials; D026902:Potassium Channel Blockers / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000502:physiology; D016548:Prosencephalon / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D002121:Calcium Channel Blockers; D026902:Potassium Channel Blockers; D044302:Receptor, Serotonin, 5-HT1B; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D005680:gamma-Aminobutyric Acid; D002118:Calcium
keywords: IPSCs; K+ channels; patch-clamp; slices