title: Presynaptic cell type-dependent regulation of GABAergic synaptic transmission by nitric oxide in rat insular cortex.
abstract: Nitric oxide (NO) is a key retrograde messenger that regulates synaptic transmission in the cerebral cortex. However, little is known about NO-induced modulatory effects and their mechanisms relative to inhibitory synaptic transmission. The present study aimed to examine the effects of NO on unitary inhibitory postsynaptic currents (uIPSCs) and to postulate the synaptic location of NO action. We performed multiple whole-cell patch-clamp recordings from rat insular cortex and divided recorded cells into three subtypes: pyramidal cells (Pyr), fast-spiking interneurons (FS), and non-FS GABAergic interneurons. In the connections from FS to Pyr (FS→Pyr), the application of S-nitroso-N-acetyl-dl-penicillamine (SNAP, 100 μM), an NO donor, suppressed uIPSC amplitudes in 31% of the connections, whereas 39% of the connections showed uIPSC facilitation. The remaining FS→Pyr connections showed little effect of SNAP on uIPSCs. An analysis of paired-pulse ratio (PPR) implied the involvement of presynaptic mechanisms in SNAP-induced effects on uIPSCs. Similar effects of SNAP were observed in FS→FS/non-FS connections; 33%, 54%, and 13% of the connections were facilitated, suppressed, and unchanged, respectively. In contrast, non-FS→Pyr or FS/non-FS showed constant uIPSC suppression by SNAP. PPR analysis supports the hypothesis that these SNAP-induced effects are mediated by presynaptic mechanisms in FS→FS/non-FS and non-FS→Pyr/FS/non-FS connections. The NO scavenger, 2-phenyl-4,4,5,5-tetramethylimidazolineoxyl-1-oxyl-3-oxide (PTIO), or the inhibitor of guanylate cyclase, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), abolished the SNAP-induced uIPSC modulation. These results suggest that NO regulation of inhibitory synaptic transmission is dependent on presynaptic cell subtypes and that, at least in part, the effects are mediated by presynaptic mechanisms.
authors.affiliation: Department of Pharmacology, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Department of Pharmacology, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan; Department of Pediatric Dentistry, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Takei
authors.affiliation: Department of Pharmacology, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan; Department of Anesthesiology, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Koyanagi
authors.affiliation: Department of Pharmacology, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan; Division of Oral and Craniomaxillofacial Research, Dental Research Center, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Koshikawa
authors.affiliation: Department of Pharmacology, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan; Division of Oral and Craniomaxillofacial Research, Dental Research Center, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan; RIKEN Center for Molecular Imaging Science, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan. Electronic address: kobayashi.masayuki@nihon-u.ac.jp.
authors.forename: M
authors.initials: M
authors.lastname: Kobayashi
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D055592:Biophysical Phenomena / Q000187:drug effects / Q000235:genetics; D002118:Calcium / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology*; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D059330:GABAergic Neurons / Q000187:drug effects / Q000502:physiology*; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D055647:Rats, Transgenic; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D009435:Synaptic Transmission / Q000502:physiology*; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000235:genetics
chemical_list: D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D007093:Imidazoles; C118623:Slc32a1 protein, rat; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C079391:2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D052248:Nitric Oxide Synthase Type I; D002118:Calcium
keywords: GABA; insular cortex; nitric oxide; postsynaptic; presynaptic; whole-cell patch-clamp