title: Sodium salicylate potentiates the GABAB-GIRK pathway to suppress rebound depolarization in neurons of the rat's medial geniculate body.
abstract: Rebound depolarization (RD) is a voltage response to the offset from pre-hyperpolarization of neuronal membrane potential, which manifests a particular form of the postsynaptic membrane potential response to inhibitory presynaptic inputs. We previously demonstrated that sodium salicylate (NaSal), a tinnitus inducer, can drastically suppress the RD in neurons of rat medial geniculate body (MGB) (Su et al, 2012; PLoS ONE 7, e46969). The purpose of the present study was to investigate the underlying cellular mechanism by using whole-cell patch-clamp recordings in rat MGB slices. NaSal (1.4 mM) had no effects on the current mediated by T-type Ca(2+) channels, indicating that it does not target these channels to suppress the RD. Instead, NaSal was shown to hyperpolarize the resting membrane potential to suppress the RD. NaSal had no effects on the current mediated by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, indicating that it does not target these channels to hyperpolarize the resting membrane potential. NaSal induced an outward leak current that could be abolished by CGP55845, a GABAB receptor blocker, or respectively by Ba(2+) and Tertiapin-Q, blockers for G-protein-gated inwardly rectifying potassium (GIRK) channels, indicating that NaSal potentiates the GABAB-GIRK pathway to hyperpolarize the resting membrane potential. Our study demonstrates that NaSal targets GABAB receptors to alter functional behaviors of MGB neurons, which may be implicated in NaSal-induced tinnitus.
authors.affiliation: CAS Key Laboratory of Brain Function and Diseases, School of Life Sciences, University of Science and Technology of China, Hefei 230027, PR China.
authors.forename: Xin-Xing
authors.initials: XX
authors.lastname: Wang
authors.affiliation: Auditory Research Laboratory, School of Life Sciences, University of Science and Technology of China, Hefei 230027, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Anhui Provincial Hospital, Affiliated to Anhui Medical University, Hefei 230001, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Luo
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Anhui Provincial Hospital, Affiliated to Anhui Medical University, Hefei 230001, PR China.
authors.forename: Jing-Wu
authors.initials: JW
authors.lastname: Sun
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: Jinsheng
authors.initials: J
authors.lastname: Zhang
authors.affiliation: CAS Key Laboratory of Brain Function and Diseases, School of Life Sciences, University of Science and Technology of China, Hefei 230027, PR China; Auditory Research Laboratory, School of Life Sciences, University of Science and Technology of China, Hefei 230027, PR China.
authors.forename: Ming
authors.initials: M
authors.lastname: Wang
authors.affiliation: CAS Key Laboratory of Brain Function and Diseases, School of Life Sciences, University of Science and Technology of China, Hefei 230027, PR China; Auditory Research Laboratory, School of Life Sciences, University of Science and Technology of China, Hefei 230027, PR China. Electronic address: linchen@ustc.edu.cn.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000378:metabolism*; D058788:GABA-B Receptor Antagonists; D059330:GABAergic Neurons / Q000187:drug effects* / Q000378:metabolism; D005829:Geniculate Bodies / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000187:drug effects* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D012980:Sodium Salicylate / Q000633:toxicity*
chemical_list: D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D058788:GABA-B Receptor Antagonists; D026902:Potassium Channel Blockers; D018080:Receptors, GABA-B; D012980:Sodium Salicylate
keywords: Brain slice; GABA(B) receptor; GIRK channel; Medial geniculate body; Rebound depolarization; Sodium salicylate