Homeostasis of inner ear fluids is crucial for sensory transduction and consists of the regulation of ion and water transport across barriers formed by epithelial and endothelial cells. Pathology of these homeostatic processes are thought to lead to endolymphatic hydrops and edema in stria vascularis. Epithelial cells in both the cochlea and the vestibular labyrinth of the inner ear are responsible for the secretion of potassium (K+), the primary cationic constituent of endolymph. It is expected that water would follow this secretion by osmotic forces and that it is therefore necessary for K+ to be reabsorbed from endolymph at exactly the same average rate in order to avoid catastrophic changes in the volume of endolymph. We propose to test the hypotheses a) that the epithelial tissues responsible for K+ secretion,can also reabsorb K+ when necessary to augment the K efflux through the sensory hair cells, thus maintaining endolymph volume; b) that the K+-secretory process is regulated by extracellular influences such as osmolarity and K+ concentration and that these act via cytosolic regulatory pathways; c) that the flux of water accompanying K+ transport is limited by the water permeability of the apical membrane and that this water permeability is under cytosolic regulation; d) that K+ secretion in the cochlea is controlled the cytosolic pH, as in the vestibular labyrinth, - and that a variety of mechanisms is involved in pH regulation; e) that vestibular transitional cells and spiral prominence cells provide another homeostatic route for the reabsorption of endolymphatic K+ and/or Na+; f) that capillary blood vessels in the cochlear lateral wall (spiral ligament and stria vascularis) and in the ampullae of the semicircular canals are part of the endothelial barrier analogous to the blood-brain barrier and this barrier is under the control of hormones and local mediators. Specific parameters to be measured include microfluorometry of pH- and calcium-sensitive dyes, cell volume and capillary permeability/diameter with digital imaging techniques, transepithelial voltage and resistance with the micro- Ussing chamber, transepithelial fluxes of K+ and Na+ with the ion- selective vibrating probe and electrical properties of cell membranes with several configurations of the patch clamp technique. These methods are well-established in this laboratory and represent powerful techniques for addressing the proposed hypotheses.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
2R01DC001098-06A1
Application #
2014445
Study Section
Hearing Research Study Section (HAR)
Project Start
1992-01-01
Project End
2002-05-31
Budget Start
1997-06-01
Budget End
1998-05-31
Support Year
6
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Father Flanagan's Boys' Home
Department
Type
DUNS #
City
Boys Town
State
NE
Country
United States
Zip Code
68010
Kudo, Takayuki; Wangemann, Philine; Marcus, Daniel C (2018) Claudin expression during early postnatal development of the murine cochlea. BMC Physiol 18:1
Miyazaki, Hiromitsu; Wangemann, Philine; Marcus, Daniel C (2016) The gastric H,K-ATPase in stria vascularis contributes to pH regulation of cochlear endolymph but not to K secretion. BMC Physiol 17:1
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Kim, Hyoung-Mi; Wangemann, Philine (2010) Failure of fluid absorption in the endolymphatic sac initiates cochlear enlargement that leads to deafness in mice lacking pendrin expression. PLoS One 5:e14041
Yamauchi, Daisuke; Nakaya, Kazuhiro; Raveendran, Nithya N et al. (2010) Expression of epithelial calcium transport system in rat cochlea and vestibular labyrinth. BMC Physiol 10:1

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