Meniere's Disease is one of the pathological entities characterized by endolymphatic hydrops of the cochlear and vestibular labyrinths. Hydrops can result from an alteration of ion transport properties of the epithelial cells bordering the endolymphatic system. Little is known about the cellular basis of the pathologic processes involved because data are lacking from normal as well as pathological systems concerning mechanisms of secretion and absorption of ions. Endolymph is unique in that it is the only extracellular fluid in the body with a high potassium (K+) concentration and low sodium (Na+) and calcium (Ca2+) concentrations, a composition that is essential to sustain normal hearing and balance. Our understanding of transport processes in the inner ear has increased enormously over the previous periods of this award. However, two epithelial regions, Reissner's membrane (RM) in the cochlea and the semicircular canal ducts (SCCD) in the vestibular labyrinth, make important contributions to the homeostasis of endolymphatic fluid composition and volume, but our understanding of their functions lags behind that of other cell types in the ear. It is proposed to study the transport processes responsible for fluxes of the ions K+, Na+, CI-, HC03-, Ca2+ and water in the vestibular labyrinth and cochlea by RM and SCCD. These investigations will utilize our established microdissection, electrophysiologic, molecular biologic and immunohistochemical techniques as well as novel extensions of these (cochlear slice preparation to better preserve function of delicate tissues during isolation, conductance scanning to study paracellular transport pathways, fluctuation analysis of epithelial currents to determine ion channel properties and RNA inhibition to knock down the expression of specific genes). The experimental design will test a series of hypotheses about RM and SCCD transport that will lead to an understanding of fundamental, key roles of these epithelia in the health and disease of hearing and balance.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC000212-26
Application #
7440234
Study Section
Auditory System Study Section (AUD)
Program Officer
Cyr, Janet
Project Start
1983-07-01
Project End
2010-06-30
Budget Start
2008-07-01
Budget End
2009-06-30
Support Year
26
Fiscal Year
2008
Total Cost
$366,248
Indirect Cost
Name
Kansas State University
Department
Anatomy/Cell Biology
Type
Schools of Veterinary Medicine
DUNS #
929773554
City
Manhattan
State
KS
Country
United States
Zip Code
66506
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
Kim, Kyunghee X; Sanneman, Joel D; Kim, Hyoung-Mi et al. (2014) Slc26a7 chloride channel activity and localization in mouse Reissner's membrane epithelium. PLoS One 9:e97191
Pondugula, Satyanarayana R; Kampalli, Suresh B; Wu, Tao et al. (2013) cAMP-stimulated Cl- secretion is increased by glucocorticoids and inhibited by bumetanide in semicircular canal duct epithelium. BMC Physiol 13:6
Yoo, Jae Chul; Kim, Hye-Young; Han, Kyu-Hee et al. (2012) Na+ absorption by Claudius' cells is regulated by purinergic signaling in the cochlea. Acta Otolaryngol 132 Suppl 1:S103-8
Kim, Sung Huhn; Marcus, Daniel C (2011) Regulation of sodium transport in the inner ear. Hear Res 280:21-9
Yamazaki, Muneharu; Kim, Kyunghee X; Marcus, Daniel C (2011) Sodium selectivity of Reissner's membrane epithelial cells. BMC Physiol 11:4
Kim, Hyoung-Mi; Wangemann, Philine (2011) Epithelial cell stretching and luminal acidification lead to a retarded development of stria vascularis and deafness in mice lacking pendrin. PLoS One 6:e17949
Kim, Kyunghee X; Marcus, Daniel C (2010) Inward-rectifier chloride currents in Reissner's membrane epithelial cells. Biochem Biophys Res Commun 394:434-8
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

Showing the most recent 10 out of 56 publications