title: Serotonin induces depolarization in lateral amygdala neurons by activation of TRPC-like current and inhibition of GIRK current depending on 5-HT(2C) receptor.
abstract: Regional differences are known in the serotonin-induced modulation of neuronal activity within the amygdala. This in vitro study in rats focuses on analyzing the ionic mechanism underlying serotonin-induced depolarization in the lateral amygdala. Serotonin depolarized membrane potential by 5 mV, which is underlain by a serotonin-induced inward current at rest with a characteristic reversal potential of -105 mV. From pharmacological experiments, the 5-HT2C subtype was singled out as the receptor subtype involved. Under blockade of K(+) channels by Ba(2+), 5-HT induced an inward current with no reversal at the range between -50 and -130 mV, which was identified as a TRPC-like current. This current was blocked by the specific phosphatidylinositol 3-kinse (PI3-kinase) inhibitor LY294002, pointing to its dependence on PI3-kinase. The Ba(2+)-sensitive component, obtained by subtraction, showed a strong outward rectification and the reversal potential of K(+), indicating that this component results from a serotonin-induced inhibition of G-protein coupled inwardly rectifying K(+) channel (GIRK) current. By wortmannin, an inhibitor of both PI3-kinase and PI4-kinase, a serotonin-induced phosphatidylinositol 4,5-bisphosphate (PIP2) depletion was revealed to underlie GIRK inhibition. Thus, the serotonin-induced current turned out to be caused by a combined occurrence of GIRK inhibition and PI3-kinase-dependent TRPC-like current. With serotonergic modulation, all these mechanisms should be recruited in lateral amygdala principal neurons and likely contribute to generation of region-specific neuronal activity patterns within the amygdala, which may at least partly implement its required role in fear and anxiety.
authors.affiliation: Department of Physiology, Kanazawa Medical University, Ishikawa 920-0293, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Yamamoto
authors.affiliation: Department of Physiology, Kanazawa Medical University, Ishikawa 920-0293, Japan.
authors.forename: Natsuki
authors.initials: N
authors.lastname: Hatano
authors.affiliation: Department of Physiology, Kanazawa Medical University, Ishikawa 920-0293, Japan.
authors.forename: Tokio
authors.initials: T
authors.lastname: Sugai
authors.affiliation: Department of Physiology, Kanazawa Medical University, Ishikawa 920-0293, Japan; Medical Research Institute, Kanazawa Medical University, Ishikawa 920-0293, Japan. Electronic address: kato@kanazawa-med.ac.jp.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Kato
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D015778:Minor Histocompatibility Antigens; D009025:Morpholines / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D017208:Rats, Wistar; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D050052:TRPC Cation Channels / Q000378:metabolism*; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D001464:Barium; D002867:Chromones; D004791:Enzyme Inhibitors; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D015778:Minor Histocompatibility Antigens; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017853:Phosphotransferases (Alcohol Group Acceptor); D026902:Potassium Channel Blockers; D044405:Receptor, Serotonin, 5-HT2C; D012701:Serotonin; D050052:TRPC Cation Channels; D000077191:Wortmannin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C402182:phosphatidylinositol phosphate 4-kinase
keywords: GIRK; Lateral amygdala; PI3-kinase; PIP2; Serotonin; TRPC