Suppression of ATP-induced excitability in rat small-diameter trigeminal ganglion neurons by activation of GABAB receptor期刊界 All Journals 搜尽天下杂志传播学术成果专业期刊搜索期刊信息化学术搜索

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Suppression of ATP-induced excitability in rat small-diameter trigeminal ganglion neurons by activation of GABAB receptor

Institution:	1. Department of Physiology, School of Life Dentistry at Tokyo, Nippon Dental University, 1-9-20, Fujimi-cho, Chiyoda-ku, Tokyo 102-8159, Japan;2. Research Center of Odontology, School of Life Dentistry at Tokyo, Nippon Dental University, 1-9-20, Fujimi-cho, Chiyoda-ku, Tokyo 102-8159, Japan;1. Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, 13th Street, Charlestown, MA 02129, USA;2. Surgical Oncology, Department of Medicine, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA;3. Department of Veterans Affairs, VA Boston Healthcare System, Boston, MA 02130, USA;4. Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA;1. Department of Oral Physiology, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea;2. Department of Pediatric Dentistry, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea;3. Department of Oral Anatomy, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea

Abstract:	The aim of the present study was to investigate whether a GABA_B 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 GABA_B receptor. Under voltage-clamp conditions (V_h = ?60 mV), 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 GABA_B 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 GABA_B 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 GABA_B receptor activation could inhibit the ATP-induced excitability of small-diameter TRG neurons activated through the P₂X₃ receptor. Thus, the interaction between P₂X₃ and GABA_B receptors of small-diameter TRG neuronal cell bodies is a potential therapeutic target for the treatment of trigeminal nociception.

Keywords:	Paracrine Trigeminal ganglion Whole-cell patch clamping GABA"} {"#name":"keyword" "$":{"id":"kw0035"} "$$":[{"#name":"text" "_":"γ-aminobutyric acid ATP"} {"#name":"keyword" "$":{"id":"kw0045"} "$$":[{"#name":"text" "_":"adenosine triphosphate SP"} {"#name":"keyword" "$":{"id":"kw0055"} "$$":[{"#name":"text" "_":"substance P CGRP"} {"#name":"keyword" "$":{"id":"kw0065"} "$$":[{"#name":"text" "_":"calcitonin gene-related peptide DRG"} {"#name":"keyword" "$":{"id":"kw0075"} "$$":[{"#name":"text" "_":"dorsal root ganglion TRG"} {"#name":"keyword" "$":{"id":"kw0085"} "$$":[{"#name":"text" "_":"trigeminal ganglion TRGs"} {"#name":"keyword" "$":{"id":"kw0095"} "$$":[{"#name":"text" "_":"trigeminal ganglia PIPES"} {"#name":"keyword" "$":{"id":"kw0105"} "$$":[{"#name":"text" "_":"piperazine-N N′-bis [2-ethanesulfonic acid] EDTA"} {"#name":"keyword" "$":{"id":"kw0115"} "$$":[{"#name":"text" "_":"ethylenediaminetetraaceticacid HEPES"} {"#name":"keyword" "$":{"id":"kw0125"} "$$":[{"#name":"text" "_":"N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid EGTA"} {"#name":"keyword" "$":{"id":"kw0135"} "$$":[{"#name":"text" "_":"ethylene glycol-bis-β-aminoethyl ether N N N′ N′-tetraaceticacid PPADS"} {"#name":"keyword" "$":{"id":"kw0145"} "$$":[{"#name":"text" "_":"pyridoxal-phosphate-6-azophenyl-27 47-disulfonic acid TTX-R"} {"#name":"keyword" "$":{"id":"kw0155"} "$$":[{"#name":"text" "_":"tetrodotoxin-resistant SGCs"} {"#name":"keyword" "$":{"id":"kw0165"} "$$":[{"#name":"text" "_":"satellite glial cells
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