title: NKCCs in the fibrocytes of the spiral ligament are silent on the unidirectional K⁺ transport that controls the electrochemical properties in the mammalian cochlea.
abstract: Unidirectional K(+) transport across the lateral cochlear wall contributes to the endocochlear potential (EP) of +80 mV in the endolymph, a property essential for hearing. The wall comprises two epithelial layers, the syncytium and the marginal cells. The basolateral surface of the former and the apical membranes of the latter face the perilymph and the endolymph, respectively. Intrastrial space (IS), an extracellular compartment between the two layers, exhibits low [K(+)] and a potential similar to the EP. This IS potential (ISP) dominates the EP and represents a K(+) diffusion potential elicited by a large K(+) gradient across the syncytial apical surface. The K(+) gradient depends on the unidirectional K(+) transport driven by Na(+),K(+)-ATPases on the basolateral surface of each layer and the concomitant Na(+),K(+),2Cl(-)-cotransporters (NKCCs) in the marginal cell layer. The NKCCs coexpressed with the Na(+),K(+)-ATPases in the syncytial layer also seem to participate in the K(+) transport. To test this hypothesis, we examined the electrochemical properties of the lateral wall with electrodes measuring [K(+)] and potential. Blocking NKCCs by perilymphatic perfusion of bumetanide suppressed the ISP. Unexpectedly and unlike the inhibition of the syncytial Na(+),K(+)-ATPases, the perfusion barely altered the electrochemical properties of the syncytium but markedly augmented [K(+)] of the IS. Consequently, the K(+) gradient decreased and the ISP declined. These observations resembled those when the marginal cells' Na(+),K(+)-ATPases or NKCCs were blocked with vascularly applied inhibitors. It is plausible that NKCCs in the marginal cells are affected by the perilymphatically perfused bumetanide, and these transporters, but not those in the syncytium, mediate the unidirectional K(+) transport.
authors.affiliation: Department of Molecular Physiology, School of Medicine, Niigata University, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Niigata, 951-8510, Japan.|Center for Transdisciplinary Research, Niigata University, Niigata, Japan.|Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Takamasa
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Department of Molecular Physiology, School of Medicine, Niigata University, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Niigata, 951-8510, Japan.|Center for Transdisciplinary Research, Niigata University, Niigata, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Nin
authors.affiliation: Department of Molecular Physiology, School of Medicine, Niigata University, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Niigata, 951-8510, Japan.|Center for Transdisciplinary Research, Niigata University, Niigata, Japan.
authors.forename: Genki
authors.initials: G
authors.lastname: Ogata
authors.affiliation: Department of Molecular Physiology, School of Medicine, Niigata University, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Niigata, 951-8510, Japan.|Center for Transdisciplinary Research, Niigata University, Niigata, Japan.|Department of Otorhinolaryngology-Head and Neck Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Uetsuka
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.|Department of Otorhinolaryngology-Head and Neck Surgery, Nara Medical University, Kashihara, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kitahara
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Inohara
authors.affiliation: Department of Medical Informatics, Niigata University Medical and Dental Hospital, Niigata, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Akazawa
authors.affiliation: Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Shizuo
authors.initials: S
authors.lastname: Komune
authors.affiliation: Division of Molecular and Cellular Pharmacology, Department of Pharmacology, Graduate School of Medicine, and The Center for Advanced Medical Engineering and Informatics, Osaka University, Suita, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kurachi
authors.affiliation: Department of Molecular Physiology, School of Medicine, Niigata University, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Niigata, 951-8510, Japan. hibinoh@med.niigata-u.ac.jp.|Center for Transdisciplinary Research, Niigata University, Niigata, Japan. hibinoh@med.niigata-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hibino
mesh_terms: D000818:Animals; D006168:Guinea Pigs; D017136:Ion Transport; D008297:Male; D008564:Membrane Potentials; D011188:Potassium / Q000378:metabolism*; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D055493:Spiral Ligament of Cochlea / Q000166:cytology / Q000378:metabolism* / Q000502:physiology
chemical_list: D028021:Sodium-Potassium-Chloride Symporters; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium