title: Developmental increase in hyperpolarization-activated current regulates intrinsic firing properties in rat vestibular ganglion cells.
abstract: The primary vestibular neurons convey afferent information from hair cells in the inner ear to the vestibular nuclei and the cerebellum. The intrinsic firing properties of vestibular ganglion cells (VGCs) are heterogeneous to sustained membrane depolarization, and undergo marked developmental changes from phasic to tonic types during the early postnatal period. Previous studies have shown that low-voltage-activated potassium channels, Kv1 and Kv7, play a critical role in determining the firing pattern of VGCs. In the present study, we explored the developmental changes in the properties of hyperpolarization-activated current (Ih) in rat VGCs and the role played by Ih in determining the firing properties of VGCs. Tonic firing VGCs showed a larger current density of Ih as compared to phasic firing VGCs, and tonic firing VGCs became phasic firing in the presence of ZD7288, an Ih channel blocker, indicating that Ih contributes to control the firing pattern of VGCs. The amplitude of Ih increased and the activation kinetics of Ih became faster during the developmental period. Analysis of developmental changes in the expression of hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels revealed that expression of HCN1 protein and its mRNA increased during the developmental period, whereas expression of HCN2-4 protein and its mRNA did not change. Our results suggest that HCN1 channels as well as Kv1 channels are critical in determining the firing pattern of rat VGCs and that developmental up-regulation of HCN1 transforms VGCs from phasic to tonic firing phenotypes.
authors.affiliation: Department of Otolaryngology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Yoshimoto
authors.affiliation: Department of Otolaryngology, Faculty of Medicine, University of Tokyo, Tokyo, Japan. Electronic address: iwashin-tky@umin.ac.jp.
authors.forename: S
authors.initials: S
authors.lastname: Iwasaki
authors.affiliation: Department of Rehabilitation for Sensory Functions, Research Institute, National Rehabilitation Center for Persons with Disabilities, Saitama, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Takago
authors.affiliation: Department of Circular Physiology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nakajima
authors.affiliation: Department of Physiology, Iwate Medical University, School of Dentistry, Iwate, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Sahara
authors.affiliation: Department of Otolaryngology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kitamura
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D017950:Ganglia, Sensory / Q000187:drug effects / Q000254:growth & development* / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D014725:Vestibular Nerve / Q000187:drug effects / Q000254:growth & development* / Q000502:physiology
chemical_list: C513836:HCN4 protein, rat; C578667:Hcn1 protein, rat; C578712:Hcn2 protein, rat; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D018377:Neurotransmitter Agents; D015221:Potassium Channels; D011743:Pyrimidines; D012333:RNA, Messenger; C082246:ICI D2788
keywords: development; hyperpolarization-activated current; vestibular ganglion