title: Computational model of a circulation current that controls electrochemical properties in the mammalian cochlea.
abstract: Sound-evoked mechanical stimuli permit endolymphatic K(+) to enter sensory hair cells. This transduction is sensitized by an endocochlear potential (EP) of +80 mV in endolymph. After depolarizing the cells, K(+) leaves hair cells in perilymph, and it is then circulated back to endolymph across the lateral cochlear wall. In theory, this process entails a continuous and unidirectional current carried by apical K(+) channels and basolateral K(+) uptake transporters in both the marginal cell and syncytial layers of the lateral wall. The transporters regulate intracellular and extracellular [K(+)], allowing the channels to form K(+) diffusion potentials across each of the two layers. These diffusion potentials govern the EP. What remains uncertain is whether these transport mechanisms accumulating across diverse cell layers make up a continuous circulation current in the lateral wall and how this current might affect the characteristics of the endolymph. To address this question, we developed an electrophysiological model that incorporates channels and transporters of the lateral wall and channels of hair cells that derive a circulation current. The simulation replicated normal experimental EP values and reproduced experimentally measured changes in the EP and intra- and extracellular [K(+)] in the lateral wall when different transporters and channels were blocked. The model predicts that, under these different conditions, the circulation current's contribution to the EP arises from different sources. Finally, our model also accurately simulated EP loss in a mouse model of a chloride channelopathy associated with deafness.
authors.affiliation: Division of Molecular and Cellular Pharmacology, Department of Pharmacology and Center for Advanced Medical Engineering and Informatics,  Osaka University, Osaka 565-0871,  Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Nin
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hibino
authors.forename: Shingo
authors.initials: S
authors.lastname: Murakami
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Suzuki
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Hisa
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kurachi
mesh_terms: D000818:Animals; D003051:Cochlea / Q000502:physiology*; D003055:Cochlear Microphonic Potentials / Q000502:physiology*; D004594:Electrophysiology; D004710:Endolymph / Q000378:metabolism; D054777:Hair Cells, Ampulla / Q000378:metabolism* / Q000502:physiology; D017136:Ion Transport / Q000502:physiology*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D051379:Mice; D008954:Models, Biological; D010498:Perilymph / Q000378:metabolism; D011188:Potassium / Q000378:metabolism
chemical_list: D011188:Potassium