title: Suppression of ATP-induced excitability in rat small-diameter trigeminal ganglion neurons by activation of GABAB receptor.
abstract: The aim of the present study was to investigate whether a GABAB receptor agonist could modulate ATP-activated neuronal excitability of nociceptive TRG neurons using perforated whole-cell patch-clamp and immunohistochemical techniques. Immunohistochemical analysis revealed that 86% of P2X3 receptor-immunoreactive, small-diameter TRG neurons co-expressed GABAB receptor. Under voltage-clamp conditions (Vh=-60mV), application of ATP activated the inward current in acutely isolated rat TRG neurons in a dose-dependent manner (10-50 μM) and this current could be blocked by pyridoxal-phosphate-6-azophenyl-27,47-disulfonic acid (PPADS) (10 μM), a selective P2 purinoreceptor antagonist. The peak amplitude of ATP-activated currents was significantly inhibited after application of GABAB receptor agonist, baclofen (10-50 μM), in a concentration-dependent and reversible manner. The baclofen-induced inhibition of ATP-activated current was abolished by co-application of 3-amino-2 (4-chlorophenyl)-2hydroxypropysufonic acid) saclofen, a GABAB receptor antagonist (50 μM). Under current-clamp conditions, application of 20 μM ATP significantly depolarized the membrane potential resulting in increased mean action potential frequencies, and these ATP-induced effects were significantly inhibited by baclofen and these effects were antagonized by co-application of saclofen. Together, the results suggested that GABAB receptor activation could inhibit the ATP-induced excitability of small-diameter TRG neurons activated through the P2X3 receptor. Thus, the interaction between P2X3 and GABAB receptors of small-diameter TRG neuronal cell bodies is a potential therapeutic target for the treatment of trigeminal nociception.
authors.affiliation: Department of Physiology, School of Life Dentistry at Tokyo, Nippon Dental University, 1-9-20, Fujimi-cho, Chiyoda-ku, Tokyo 102-8159, Japan. Electronic address: m-takeda@tokyo.ndu.ac.jp.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Takeda
authors.forename: Mizuho
authors.initials: M
authors.lastname: Ikeda
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takahashi
authors.forename: Takuya
authors.initials: T
authors.lastname: Kanazawa
authors.forename: Masanori
authors.initials: M
authors.lastname: Nasu
authors.forename: Shigeji
authors.initials: S
authors.lastname: Matsumoto
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D018080:Receptors, GABA-B / Q000378:metabolism*; D058477:Receptors, Purinergic P2X3 / Q000378:metabolism; D012668:Trigeminal Ganglion / Q000166:cytology*
chemical_list: D018755:GABA Agonists; D018756:GABA Antagonists; D018080:Receptors, GABA-B; D058477:Receptors, Purinergic P2X3; D000255:Adenosine Triphosphate; D001418:Baclofen; C080629:saclofen
keywords: ATP; CGRP; DRG; EDTA; EGTA; GABA; GABA(B) receptor; HEPES; N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid; P(2)X3 receptor; PIPES; PPADS; Paracrine; SGCs; SP; TRG; TRGs; TTX-R; Trigeminal ganglion; Whole-cell patch clamping; adenosine triphosphate; calcitonin gene-related peptide; dorsal root ganglion; ethylene glycol-bis-β-aminoethyl ether N,N,N′,N′-tetraaceticacid; ethylenediaminetetraaceticacid; piperazine-N,N′-bis [2-ethanesulfonic acid]; pyridoxal-phosphate-6-azophenyl-27,47-disulfonic acid; satellite glial cells; substance P; tetrodotoxin-resistant; trigeminal ganglia; trigeminal ganglion; γ-aminobutyric acid