title: Sodium channel diversity in the vestibular ganglion: NaV1.5, NaV1.8, and tetrodotoxin-sensitive currents.
abstract: Firing patterns differ between subpopulations of vestibular primary afferent neurons. The role of sodium (NaV) channels in this diversity has not been investigated because NaV currents in rodent vestibular ganglion neurons (VGNs) were reported to be homogeneous, with the voltage dependence and tetrodotoxin (TTX) sensitivity of most neuronal NaV channels. RT-PCR experiments, however, indicated expression of diverse NaV channel subunits in the vestibular ganglion, motivating a closer look. Whole cell recordings from acutely dissociated postnatal VGNs confirmed that nearly all neurons expressed NaV currents that are TTX-sensitive and have activation midpoints between -30 and -40 mV. In addition, however, many VGNs expressed one of two other NaV currents. Some VGNs had a small current with properties consistent with NaV1.5 channels: low TTX sensitivity, sensitivity to divalent cation block, and a relatively negative voltage range, and some VGNs showed NaV1.5-like immunoreactivity. Other VGNs had a current with the properties of NaV1.8 channels: high TTX resistance, slow time course, and a relatively depolarized voltage range. In two NaV1.8 reporter lines, subsets of VGNs were labeled. VGNs with NaV1.8-like TTX-resistant current also differed from other VGNs in the voltage dependence of their TTX-sensitive currents and in the voltage threshold for spiking and action potential shape. Regulated expression of NaV channels in primary afferent neurons is likely to selectively affect firing properties that contribute to the encoding of vestibular stimuli.
authors.affiliation: Speech and Hearing Bioscience and Technology Program, Harvard-Massachusetts Institute of Technology Health Sciences and Technology Program, Cambridge, Massachusetts; Eaton-Peabody Laboratories, Massachusetts Eye and Ear, and Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts;
authors.forename: Xiao-Ping
authors.identifier: 0000-0003-3449-7601
authors.initials: XP
authors.lastname: Liu
authors.affiliation: Otorhinolaryngology and Neuroscience, Baylor College of Medicine, Houston, Texas;
authors.forename: Julian R A
authors.identifier: 0000-0003-0778-0196
authors.initials: JR
authors.lastname: Wooltorton
authors.affiliation: Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, Illinois;
authors.forename: Sophie
authors.identifier: 0000-0001-8256-8692
authors.initials: S
authors.lastname: Gaboyard-Niay
authors.affiliation: Dana-Farber Cancer Institute, Boston, Massachusetts; Department of Neurobiology, Harvard Medical School, Boston, Massachusetts; and.
authors.forename: Fu-Chia
authors.identifier: 0000-0002-7098-3212
authors.initials: FC
authors.lastname: Yang
authors.affiliation: Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, Illinois; Department of Otolaryngology-Head and Neck Surgery, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Anna
authors.identifier: 0000-0001-6259-0294
authors.initials: A
authors.lastname: Lysakowski
authors.affiliation: Eaton-Peabody Laboratories, Massachusetts Eye and Ear, and Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts; Department of Neurobiology, Harvard Medical School, Boston, Massachusetts; and Department of Otolaryngology-Head and Neck Surgery, University of Illinois at Chicago, Chicago, Illinois eatock@uchicago.edu.
authors.forename: Ruth Anne
authors.identifier: 0000-0001-7547-2051
authors.initials: RA
authors.lastname: Eatock
mesh_terms: D000200:Action Potentials; D000818:Animals; D002478:Cells, Cultured; D017950:Ganglia, Sensory / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics / Q000378:metabolism*; D062559:NAV1.8 Voltage-Gated Sodium Channel / Q000235:genetics / Q000378:metabolism*; D009475:Neurons, Afferent / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology*; D014722:Vestibule, Labyrinth / Q000294:innervation*
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; D062559:NAV1.8 Voltage-Gated Sodium Channel; C568319:Scn10a protein, rat; C568322:Scn5a protein, rat; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin
keywords: NaV1.5; NaV1.8; action potential; sodium channel; tetrodotoxin; vestibular afferent; vestibular ganglion