| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Anatomy & Physiology, Kansas State University, Manhattan, Kansas, United States
2 Anatomy & Physiology, Kansas State University, Kansas, United States
* To whom correspondence should be addressed. E-mail: wange{at}vet.ksu.edu.
Pendred syndrome, characterized by childhood deafness and post-puberty goiter, is caused by mutations of SLC26A4, which codes for the anion exchanger pendrin. The goal of the present study was to determine how loss of pendrin leads to hair cell degeneration and deafness. We evaluated pendrin function by ratiometric micro-fluorometry, hearing by auditory brain stem recordings and expression of K+ and Ca2+ channels by confocal immunohistochemistry. Cochlear pH and Ca2+ concentrations and the endocochlear potential (EP) were measured with double-barreled ion-selective microelectrodes. Pendrin in the cochlea was characterized as a formate-permeable and DIDS-sensitive anion exchanger that is likely to mediate HCO3- secretion into endolymph. Hence endolymph in Slc26a4+/- mice was more alkaline than perilymph and loss of the pendrin in Slc26a4-/- lead to an acidification of endolymph. Stria vascularis of Slc26a4-/- expressed the K+ channel Kcnj10 and generated a small endocochlear potential before the normal onset of hearing at postnatal day 12. This small potential and the expression of Kcnj10 were lost during further development and Slc26a4-/- mice did not acquire hearing. Endolymphatic acidification may be responsible for inhibition of Ca2+ reabsorption from endolymph via the acid-sensitive epithelial Ca2+ channels Trpv5 and Trpv6. Hence, the endolymphatic Ca2+ concentration was found elevated in Slc26a4-/- mice. This elevation may inhibit sensory transduction necessary for hearing and promote the degeneration of the sensory hair cells. Degeneration of the hair cells closes a window of opportunity to restore the normal development of hearing in Slc26a4-/- mice and possibly human patients suffering from Pendred syndrome.
This article has been cited by other articles:
|
|
 |
|
  P. Wangemann, H.-M. Kim, S. Billings, K. Nakaya, X. Li, R. Singh, D. S. Sharlin, D. Forrest, D. C. Marcus, and P. Fong Developmental delays consistent with cochlear hypothyroidism contribute to failure to develop hearing in mice lacking Slc26a4/pendrin expression Am J Physiol Renal Physiol, November 1, 2009; 297(5): F1435 - F1447. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Zdebik, P. Wangemann, and T. J. Jentsch Potassium Ion Movement in the Inner Ear: Insights from Genetic Disease and Mouse Models Physiology, October 1, 2009; 24(5): 307 - 316. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Runge-Samuelson and M. Olivier The rocky road toward clinical genetic testing: insights into the physio-genetic basis of hearing loss Physiol Genomics, October 1, 2009; 39(2): 83 - 84. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Dossena, S. Rodighiero, V. Vezzoli, C. Nofziger, E. Salvioni, M. Boccazzi, E. Grabmayer, G. Botta, G. Meyer, L. Fugazzola, et al. Functional characterization of wild-type and mutated pendrin (SLC26A4), the anion transporter involved in Pendred syndrome J. Mol. Endocrinol., September 1, 2009; 43(3): 93 - 103. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Dai, A. K. Stewart, F. Chebib, A. Hsu, J. Rozenfeld, D. Huang, D. Kang, V. Lip, H. Fang, H. Shao, et al. Distinct and novel SLC26A4/Pendrin mutations in Chinese and U.S. patients with nonsyndromic hearing loss Physiol Genomics, August 7, 2009; 38(3): 281 - 290. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Ohana, D. Yang, N. Shcheynikov, and S. Muallem Diverse transport modes by the solute carrier 26 family of anion transporters J. Physiol., May 15, 2009; 587(10): 2179 - 2185. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Pera, S. Dossena, S. Rodighiero, M. Gandia, G. Botta, G. Meyer, F. Moreno, C. Nofziger, C. Hernandez-Chico, and M. Paulmichl Functional assessment of allelic variants in the SLC26A4 gene involved in Pendred syndrome and nonsyndromic EVA PNAS, November 25, 2008; 105(47): 18608 - 18613. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Shcheynikov, D. Yang, Y. Wang, W. Zeng, L. P. Karniski, I. So, S. M. Wall, and S. Muallem The Slc26a4 transporter functions as an electroneutral Cl-/I-/HCO3- exchanger: role of Slc26a4 and Slc26a6 in I- and HCO3- secretion and in regulation of CFTR in the parotid duct J. Physiol., August 15, 2008; 586(16): 3813 - 3824. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J S Yoon, H-J Park, S-Y Yoo, W Namkung, M J Jo, S K Koo, H-Y Park, W-S Lee, K H Kim, and M G Lee Heterogeneity in the processing defect of SLC26A4 mutants J. Med. Genet., July 1, 2008; 45(7): 411 - 419. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Dorwart, N. Shcheynikov, D. Yang, and S. Muallem The Solute Carrier 26 Family of Proteins in Epithelial Ion Transport Physiology, April 1, 2008; 23(2): 104 - 114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Singh and P. Wangemann Free radical stress-mediated loss of Kcnj10 protein expression in stria vascularis contributes to deafness in Pendred syndrome mouse model Am J Physiol Renal Physiol, January 1, 2008; 294(1): F139 - F148. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. P. Hughey and T. R. Kleyman Functional cross talk between ENaC and pendrin Am J Physiol Renal Physiol, November 1, 2007; 293(5): F1439 - F1440. [Full Text] [PDF]
|
|
|
|
 |
|
 F. Lang, V. Vallon, M. Knipper, and P. Wangemann Functional significance of channels and transporters expressed in the inner ear and kidney Am J Physiol Cell Physiol, October 1, 2007; 293(4): C1187 - C1208. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
