title: The unique ion permeability profile of cochlear fibrocytes and its contribution to establishing their positive resting membrane potential.
abstract: Eukaryotic cells exhibit negative resting membrane potential (RMP) owing to the high K(+) permeability of the plasma membrane and the asymmetric [K(+)] between the extracellular and intracellular compartments. However, cochlear fibrocytes, which comprise the basolateral surface of a multilayer epithelial-like tissue, exhibit a RMP of +5 to +12 mV in vivo. This positive RMP is critical for the formation of an endocochlear potential (EP) of +80 mV in a K(+)-rich extracellular fluid, endolymph. The epithelial-like tissue bathes fibrocytes in a regular extracellular fluid, perilymph, and apically faces the endolymph. The EP, which is essential for hearing, represents the potential difference across the tissue. Using in vivo electrophysiological approaches, we describe a potential mechanism underlying the unusual RMP of guinea pig fibrocytes. The RMP was +9.0 ± 3.7 mV when fibrocytes were exposed to an artificial control perilymph (n = 28 cochleae). Perilymphatic perfusion of a solution containing low [Na(+)] (1 mM) markedly hyperpolarized the RMP to -31.1 ± 11.2 mV (n = 10; p < 0.0001 versus the control, Tukey-Kramer test after one-way ANOVA). Accordingly, the EP decreased. Little change in RMP was observed when the cells were treated with a high [K(+)] of 30 mM (+10.4 ± 2.3 mV; n = 7; p = 0.942 versus the control). During the infusion of a low [Cl(-)] solution (2.4 mM), the RMP moderately hyperpolarized to -0.9 ± 3.4 mV (n = 5; p < 0.01 versus the control), although the membranes, if governed by Cl(-) permeability, should be depolarized. These observations imply that the fibrocyte membranes are more permeable to Na(+) than K(+) and Cl(-), and this unique profile and [Na(+)] gradient across the membranes contribute to the positive RMP.
authors.affiliation: Department of Molecular Physiology, Niigata University School of Medicine, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Niigata, 951-8510, Japan.|Center for Transdisciplinary Research, Niigata University, Niigata, Niigata, 950-2181, Japan.|Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
authors.forename: Takamasa
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Department of Molecular Physiology, Niigata University School of Medicine, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Niigata, 951-8510, Japan.|Center for Transdisciplinary Research, Niigata University, Niigata, Niigata, 950-2181, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Nin
authors.affiliation: Division of Molecular and Cellular Pharmacology, Department of Pharmacology, Osaka University, Suita, Osaka, 565-0871, Japan.|The Center for Advanced Medical Engineering and Informatics, Osaka University, Suita, Osaka, 565-0871, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Murakami
authors.affiliation: Department of Molecular Physiology, Niigata University School of Medicine, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Niigata, 951-8510, Japan.|Center for Transdisciplinary Research, Niigata University, Niigata, Niigata, 950-2181, Japan.
authors.forename: Genki
authors.initials: G
authors.lastname: Ogata
authors.affiliation: Department of Molecular Physiology, Niigata University School of Medicine, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Niigata, 951-8510, Japan.|Center for Transdisciplinary Research, Niigata University, Niigata, Niigata, 950-2181, Japan.|Department of Otorhinolaryngology-Head and Neck Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Uetsuka
authors.affiliation: Department of Electrical and Electronics Engineering, Niigata University, Niigata, 950-2181, Niigata, Japan.|AMED-CREST, AMED, Niigata, Japan.
authors.forename: Samuel
authors.initials: S
authors.lastname: Choi
authors.affiliation: Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Inohara
authors.affiliation: Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.|Division of Otolaryngology-Head and Neck Surgery, Yuaikai Oda Hospital, Saga, 849-1392, Japan.
authors.forename: Shizuo
authors.initials: S
authors.lastname: Komune
authors.affiliation: Division of Molecular and Cellular Pharmacology, Department of Pharmacology, Osaka University, Suita, Osaka, 565-0871, Japan.|The Center for Advanced Medical Engineering and Informatics, Osaka University, Suita, Osaka, 565-0871, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kurachi
authors.affiliation: Department of Molecular Physiology, Niigata University School of Medicine, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Niigata, 951-8510, Japan. hibinoh@med.niigata-u.ac.jp.|Center for Transdisciplinary Research, Niigata University, Niigata, Niigata, 950-2181, Japan. hibinoh@med.niigata-u.ac.jp.|AMED-CREST, AMED, Niigata, Japan. hibinoh@med.niigata-u.ac.jp.
authors.forename: Hiroshi
authors.identifier: 0000-0003-0688-1489
authors.initials: H
authors.lastname: Hibino
mesh_terms: D000818:Animals; D002463:Cell Membrane Permeability; D002712:Chlorides / Q000378:metabolism; D003051:Cochlea / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D004710:Endolymph / Q000378:metabolism; D006168:Guinea Pigs; D017136:Ion Transport; D008297:Male; D008564:Membrane Potentials; D010498:Perilymph / Q000378:metabolism; D011188:Potassium / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*
chemical_list: D002712:Chlorides; D012964:Sodium; D011188:Potassium
keywords: Endocochlear potential; Inner ear; Na+ permeability; Resting membrane potential; Spiral ligament