title: The unique electrical properties in an extracellular fluid of the mammalian cochlea; their functional roles, homeostatic processes, and pathological significance.
abstract: The cochlea of the mammalian inner ear contains an endolymph that exhibits an endocochlear potential (EP) of +80 mV with a [K(+)] of 150 mM. This unusual extracellular solution is maintained by the cochlear lateral wall, a double-layered epithelial-like tissue. Acoustic stimuli allow endolymphatic K(+) to enter sensory hair cells and excite them. The positive EP accelerates this K(+) influx, thereby sensitizing hearing. K(+) exits from hair cells and circulates back to the lateral wall, which unidirectionally transports K(+) to the endolymph. In vivo electrophysiological assays demonstrated that the EP stems primarily from two K(+) diffusion potentials yielded by [K(+)] gradients between intracellular and extracellular compartments in the lateral wall. Such gradients seem to be controlled by ion channels and transporters expressed in particular membrane domains of the two layers. Analyses of human deafness genes and genetically modified mice suggested the contribution of these channels and transporters to EP and hearing. A computational model, which reconstitutes unidirectional K(+) transport by incorporating channels and transporters in the lateral wall and connects this transport to hair cell transcellular K(+) fluxes, simulates the circulation current flowing between the endolymph and the perilymph. In this model, modulation of the circulation current profile accounts for the processes leading to EP loss under pathological conditions. This article not only summarizes the unique physiological and molecular mechanisms underlying homeostasis of the EP and their pathological relevance but also describes the interplay between EP and circulation current.
authors: Department of Molecular Physiology, Niigata University School of Medicine, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Niigata, 951-8510, Japan.
authors: Fumiaki
authors: F
authors: Nin
authors: 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, 950-2181, Japan.|Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
authors: Takamasa
authors: T
authors: Yoshida
authors: Department of Molecular Physiology, Niigata University School of Medicine, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Niigata, 951-8510, Japan.
authors: Seishiro
authors: S
authors: Sawamura
authors: 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, 950-2181, Japan.
authors: Genki
authors: G
authors: Ogata
authors: Department of Molecular Physiology, Niigata University School of Medicine, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Niigata, 951-8510, Japan.
authors: Takeru
authors: T
authors: Ota
authors: Department of Molecular Physiology, Niigata University School of Medicine, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Niigata, 951-8510, Japan.
authors: Taiga
authors: T
authors: Higuchi
authors: Division of Molecular and Cellular Pharmacology, Department of Pharmacology, Osaka University, Osaka, 565-0871, Japan.|Center for Advanced Medical Engineering and Informatics, Graduate School of Medicine, Osaka University, Osaka, 565-0871, Japan.|Department of Physiology, School of Medicine, Toho University, Tokyo, 143-8540, Japan.
authors: Shingo
authors: S
authors: Murakami
authors: Department of Otolaryngology, Kindai University Faculty of Medicine, Osaka, 589-8511, Japan.
authors: Katsumi
authors: K
authors: Doi
authors: Division of Molecular and Cellular Pharmacology, Department of Pharmacology, Osaka University, Osaka, 565-0871, Japan.|Center for Advanced Medical Engineering and Informatics, Graduate School of Medicine, Osaka University, Osaka, 565-0871, Japan.
authors: Yoshihisa
authors: Y
authors: Kurachi
authors: 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, 950-2181, Japan. hibinoh@med.niigata-u.ac.jp.|AMED-CREST, AMED, Niigata, Japan. hibinoh@med.niigata-u.ac.jp.
authors: Hiroshi
authors: H
authors: Hibino
mesh_terms: D000200:Action Potentials; D000818:Animals; D003051:Cochlea / Q000378:metabolism / Q000502:physiology*; D003638:Deafness / Q000378:metabolism / Q000503:physiopathology*; D045604:Extracellular Fluid / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D011188:Potassium / Q000378:metabolism
chemical_list: D011188:Potassium
keywords: Cochlea; Computer simulation; Electrophysiology; Endocochlear potential; Hearing; Ion concentrations; K+ transport