QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, October 5, 2005, 25(40):9285-9293; doi:10.1523/JNEUROSCI.2110-05.2005

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (29) Citing Articles via Google Scholar Google Scholar Articles by Beisel, K. W. Articles by Fritzsch, B. Search for Related Content PubMed PubMed Citation Articles by Beisel, K. W. Articles by Fritzsch, B.

 Previous Article  |  Next Article 

Cellular/Molecular
Differential Expression of KCNQ4 in Inner Hair Cells and Sensory Neurons Is the Basis of Progressive High-Frequency Hearing Loss

Kirk W. Beisel,¹ Sonia M. Rocha-Sanchez,¹ Ken A. Morris,¹ Liping Nie,³ Feng Feng,¹ Bechara Kachar,² Ebenezer N. Yamoah,³ and Bernd Fritzsch¹

¹Department of Biomedical Sciences, Creighton University, Omaha, Nebraska 68178, ²Section on Structural Cell Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892, and ³Department of Otolaryngology, Center for Neuroscience, University of California, Davis, California 95616

Human KCNQ4 mutations known as DFNA2 cause non-syndromic, autosomal-dominant, progressive high-frequency hearing loss in which the cellular and molecular basis is unclear. We provide immunofluorescence data showing that Kcnq4 expression in the adult cochlea has both longitudinal (base to apex) and radial (inner to outer hair cells) gradients. The most intense labeling is in outer hair cells at the apex and in inner hair cells as well as spiral ganglion neurons at the base. Spatiotemporal expression studies show increasing intensity of KCNQ4 protein labeling from postnatal day 21 (P21) to P120 mice that is most apparent in inner hair cells of the middle turn. We have identified four alternative splice variants of Kcnq4 in mice. The alternative use of exons 9-11 produces three transcript variants (v1-v3), whereas the fourth variant (v4) skips all three exons; all variants have the same amino acid sequence at the C termini. Both reverse transcription-PCR and quantitative PCR analyses demonstrate that these variants have differential expression patterns along the length of the mouse organ of Corti and spiral ganglion neurons. Our expression data suggest that the primary defect leading to high-frequency loss in DFNA2 patients may be attributable to high levels of the dysfunctional Kcnq4_v3 variant in the spiral ganglion and inner hair cells in the basal hook region. Progressive hearing loss associated with aging may result from an increasing mutational load expansion toward the apex in inner hair cells and spiral ganglion neurons.

Key words: potassium channel; Kcnq4; inner ear; hair cells; progressive high-frequency hearing loss; immunofluorescence; quantitative RT-PCR

---

Received May 25, 2005; revised August 19, 2005; accepted August 21, 2005.

This article has been cited by other articles:

				S. Joshi, V. Sedivy, D. Hodyc, J. Herget, and A. M. Gurney KCNQ Modulators Reveal a Key Role for KCNQ Potassium Channels in Regulating the Tone of Rat Pulmonary Artery Smooth Muscle J. Pharmacol. Exp. Ther., April 1, 2009; 329(1): 368 - 376. [Abstract] [Full Text] [PDF]

				A. D. Sousa, L. R. Andrade, F. T. Salles, A. M. Pillai, E. D. Buttermore, M. A. Bhat, and B. Kachar The Septate Junction Protein Caspr Is Required for Structural Support and Retention of KCNQ4 at Calyceal Synapses of Vestibular Hair Cells J. Neurosci., March 11, 2009; 29(10): 3103 - 3108. [Abstract] [Full Text] [PDF]

				M. Mustapha, Q. Fang, T.-W. Gong, D. F. Dolan, Y. Raphael, S. A. Camper, and R. K. Duncan Deafness and Permanently Reduced Potassium Channel Gene Expression and Function in Hypothyroid Pit1dw Mutants J. Neurosci., January 28, 2009; 29(4): 1212 - 1223. [Abstract] [Full Text] [PDF]

				R. J. Pauw, F. J. W. van Drunen, R. W. J. Collin, P. L. M. Huygen, H. Kremer, and C. W. R. J. Cremers Audiometric Characteristics of a Dutch Family Linked to DFNA15 With a Novel Mutation (p.L289F) in POU4F3 Arch Otolaryngol Head Neck Surg, March 1, 2008; 134(3): 294 - 300. [Abstract] [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]

				T. Xu, L. Nie, Y. Zhang, J. Mo, W. Feng, D. Wei, E. Petrov, L. E. Calisto, B. Kachar, K. W. Beisel, et al. Roles of Alternative Splicing in the Functional Properties of Inner Ear-specific KCNQ4 Channels J. Biol. Chem., August 17, 2007; 282(33): 23899 - 23909. [Abstract] [Full Text] [PDF]

				J. R. Holt, E. A. Stauffer, D. Abraham, and G. S. G. Geleoc Dominant-Negative Inhibition of M-Like Potassium Conductances in Hair Cells of the Mouse Inner Ear J. Neurosci., August 15, 2007; 27(33): 8940 - 8951. [Abstract] [Full Text] [PDF]

				L. I. Brueggemann, C. J. Moran, J. A. Barakat, J. Z. Yeh, L. L. Cribbs, and K. L. Byron Vasopressin stimulates action potential firing by protein kinase C-dependent inhibition of KCNQ5 in A7r5 rat aortic smooth muscle cells Am J Physiol Heart Circ Physiol, March 1, 2007; 292(3): H1352 - H1363. [Abstract] [Full Text] [PDF]

				H. Hibino and Y. Kurachi Molecular and physiological bases of the k+ circulation in the Mammalian inner ear. Physiology, October 1, 2006; 21: 336 - 345. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help