title: Activation of 5-HT2A/C receptor reduces glycine receptor-mediated currents in cultured auditory cortical neurons.
abstract: Glycine receptors (GlyRs) permeable to chloride only mediate tonic inhibition in the cerebral cortex where glycinergic projection is completely absent. The functional modulation of GlyRs was largely studied in subcortical brain regions with glycinergic transmissions, but the function of cortical GlyRs was rarely addressed. Serotonin could broadly modulate many ion channels through activating 5-HT2 receptor, but whether cortical GlyRs are subjected to serotonergic modulation remains unexplored. The present study adopted patch clamp recordings to examine functional regulation of strychnine-sensitive GlyRs currents in cultured cortical neurons by DOI (2,5-Dimethoxy-4-iodoamphetamine), a 5-HT2A/C receptor agonist. DOI caused a concentration-dependent reduction of GlyR currents with unchanged reversal potential. This reduction was blocked by the selective receptor antagonists (ritanserin and risperidone) and G protein inhibitor (GDP-β-s) demonstrated that the reducing effect of DOI on GlyR current required the activation of 5-HT2A/C receptors. Strychnine-sensitive tonic currents revealed the inhibitory tone mediated by nonsynaptic GlyRs, and DOI similarly reduced the tonic inhibition. The impaired microtube-dependent trafficking or clustering of GlyRs was thought to be involved in that nocodazole as a microtube depolymerizing drug largely blocked the inhibition mediated by 5-HT2A/C receptors. Our results suggested that activation of 5-HT2A/C receptors might suppress cortical tonic inhibition mediated by GlyRs, and the findings would provide important insight into serotonergic modulation of tonic inhibition mediated by GlyRs, and possibly facilitate to develop the therapeutic treatment of neurological diseases such as tinnitus through regulating cortical GlyRs.
authors.affiliation: Department of Otolaryngology, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, 230001, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Luo
authors.affiliation: Key Laboratory of Regenerative Biology, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, Guangdong, China.|Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou, 510530, Guangdong, China.
authors.forename: Lingli
authors.initials: L
authors.lastname: Hu
authors.affiliation: Key Laboratory of Regenerative Biology, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, Guangdong, China.|Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou, 510530, Guangdong, China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Liu
authors.affiliation: Key Laboratory of Regenerative Biology, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, Guangdong, China.|Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou, 510530, Guangdong, China.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Key Laboratory of Regenerative Biology, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, Guangdong, China. wang_haitao@gibh.ac.cn.|Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou, 510530, Guangdong, China. wang_haitao@gibh.ac.cn.
authors.forename: Haitao
authors.initials: H
authors.lastname: Wang
mesh_terms: D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001303:Auditory Cortex / Q000378:metabolism*; D002478:Cells, Cultured; D019204:GTP-Binding Proteins / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D007473:Ion Channels / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D015739:Nocodazole / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*; D018009:Receptors, Glycine / Q000378:metabolism*; D018967:Risperidone / Q000494:pharmacology; D016713:Ritanserin / Q000494:pharmacology; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology; D013331:Strychnine / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D050257:Tubulin Modulators / Q000494:pharmacology
chemical_list: D000662:Amphetamines; D007473:Ion Channels; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D018009:Receptors, Glycine; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D013873:Thionucleotides; D050257:Tubulin Modulators; D016713:Ritanserin; D006153:Guanosine Diphosphate; C023427:guanosine 5'-O-(2-thiodiphosphate); D019204:GTP-Binding Proteins; D013331:Strychnine; D018967:Risperidone; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D015739:Nocodazole
keywords: 5-HT2A/C receptors; Auditory cortex; Glycine receptors; Patch clamp