title: α(5)GABA(A) receptors mediate primary afferent fiber tonic excitability in the turtle spinal cord.
abstract: γ-Amino butyric acid (GABA) plays a key role in the regulation of central nervous system by activating synaptic and extrasynaptic GABAA receptors. It is acknowledged that extrasynaptic GABAA receptors located in the soma, dendrites, and axons may be activated tonically by low extracellular GABA concentrations. The activation of these receptors produces a persistent conductance that can hyperpolarize or depolarize nerve cells depending on the Cl(-) equilibrium potential. In an in vitro preparation of the turtle spinal cord we show that extrasynaptic α5GABAA receptors mediate the tonic state of excitability of primary afferents independently of the phasic primary afferent depolarization mediated by synaptic GABAA receptors. Blockade of α5GABAA receptors with the inverse agonist L-655,708 depressed the dorsal root reflex (DRR) without affecting the phasic increase in excitability of primary afferents. Using RT-PCR and Western blotting, we corroborated the presence of the mRNA and the α5GABAA protein in the dorsal root ganglia of the turtle spinal cord. The receptors were localized in primary afferents in dorsal root, dorsal root ganglia, and peripheral nerve terminals using immunoconfocal microscopy. Considering the implications of the DRR in neurogenic inflammation, α5GABAA receptors may serve as potential pharmacological targets for the treatment of pain.
authors: Department of Physiology, Biophysics and Neuroscience, Center for Research and Advanced Studies of the National Polytechnic Institute (Cinvestav-IPN), Mexico City, Mexico;
authors: Emanuel
authors: E
authors: Loeza-Alcocer
authors: Martha
authors: M
authors: Canto-Bustos
authors: Justo
authors: J
authors: Aguilar
authors: Ricardo
authors: R
authors: González-Ramírez
authors: Ricardo
authors: R
authors: Felix
authors: Rodolfo
authors: R
authors: Delgado-Lezama
mesh_terms: D000200:Action Potentials; D000818:Animals; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D059330:GABAergic Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism / Q000502:physiology*; D014426:Turtles
chemical_list: D018755:GABA Agonists; D018756:GABA Antagonists; D012333:RNA, Messenger; D011963:Receptors, GABA-A
keywords: GABAA receptors; primary afferents; spinal cord