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4. Helios is a key transcriptional regulator of outer hair cell maturation

Author

Chessum, Lauren, Matern, Maggie S., Kelly, Michael C., Johnson, Stuart L., Ogawa, Yoko, Milon, Beatrice, McMurray, Mark, Driver, Elizabeth C., Parker, Andrew, Song, Yang, Codner, Gemma, Esapa, Christopher T., Prescott, Jack, Trent, Graham, Wells, Sara, Dragich, Abigail K., Frolenkov, Gregory I., Kelley, Matthew W., Marcotti, Walter, Brown, Steve D. M., Elkon, Ran, Bowl, Michael R., and Hertzano, Ronna

Published
2018
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7. Unbalanced bidirectional radial stiffness gradients within the organ of Corti promoted by TRIOBP

Author

Babahosseini, Hesam, primary, Belyantseva, Inna A., additional, Yousaf, Rizwan, additional, Tona, Risa, additional, Hadi, Shadan, additional, Inagaki, Sayaka, additional, Wilson, Elizabeth, additional, Kitajiri, Shin-ichiro, additional, Frolenkov, Gregory I., additional, Friedman, Thomas B., additional, and Cartagena-Rivera, Alexander X., additional

Published
2022
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9. Tricellulin deficiency affects tight junction architecture and cochlear hair cells

Author

Nayak, Gowri, Lee, Sue I., Yousaf, Rizwan, Edelmann, Stephanie E., Trincot, Claire, Van Itallie, Christina M., Sinha, Ghanshyam P., Rafeeq, Maria, Jones, Sherri M., Belyantseva, Inna A., Anderson, James M., Forge, Andrew, Frolenkov, Gregory I., and Riazuddin, Saima

Subjects
Hair cells (Mechanoreceptors) -- Physiological aspects -- Research, Cell junctions -- Physiological aspects -- Research, Epithelial cells -- Physiological aspects -- Research, Hearing loss -- Research, Junctional complexes (Epithelium) -- Physiological aspects -- Research, Health care industry
Abstract

The two compositionally distinct extracellular cochlear fluids, endolymph and perilymph, are separated by tight junctions that outline the scala media and reticular lamina. Mutations in TRIC (also known as MARVELD2), which encodes a tricellular tight junction protein known as tricellulin, lead to nonsyndromic hearing loss (DFNB49). We generated a knockin mouse that carries a mutation orthologous to the TRIC coding mutation linked to DFNB49 hearing loss in humans. Tricellulin was absent from the tricellular junctions in the inner ear epithelia of the mutant animals, which developed rapidly progressing hearing loss accompanied by loss of mechanosensory cochlear hair cells, while the endocochlear potential and paracellular permeability of a biotin-based tracer in the stria vascularis were unaltered. Freeze-fracture electron microscopy revealed disruption of the strands of intramembrane particles connecting bicellular and tricellular junctions in the inner ear epithelia of tricellulin-deficient mice. These ultrastructural changes may selectively affect the paracellular permeability of ions or small molecules, resulting in a toxic microenvironment for cochlear hair cells. Consistent with this hypothesis, hair cell loss was rescued in tricellulin-deficient mice when generation of normal endolymph was inhibited by a concomitant deletion of the transcription factor, Pou3f4. Finally, comprehensive phenotypic screening showed a broader pathological phenotype in the mutant mice, which highlights the non-redundant roles played by tricellulin., Introduction Epithelial cells outline the lumen and surfaces of organs in the body and most commonly act as barriers between two different physiological environments. The barrier property of epithelial cells [...]

Published
2013
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11. [gamma]-Actin is required for cytoskeletal maintenance but not development

Author

Belyantseva, Inna A., Perrin, Benjamin J., Sonnemann, Kevin J., Zhu, Mei, Stepanyan, Ruben, McGee, JoAnn, Frolenkov, Gregory I., Walsh, Edward J., Friderici, Karen H., Friedman, Thomas B., and Ervasti, James M.

Subjects
Actin -- Health aspects, Actin -- Properties, Cytoskeleton -- Properties, Cytoskeleton -- Health aspects, Cytology -- Research, Science and technology
Abstract

[[beta].sub.cyto]-Actin and [[gamma].sub.cyto]-actin are ubiquitous proteins thought to be essential building blocks of the cytoskeleton in all non-muscle cells. Despite this widely held supposition, we show that [[gamma].sub.cyto]-actin null mice ([Actg1.sup.-/-]) are viable. However, they suffer increased mortality and show progressive hearing loss during adulthood despite compensatory up-regulation of [[beta].sub.cyto]-actin. The surprising viability and normal hearing of young [Actg1.sup.-/-] mice means that [[beta].sub.cyto]-actin can likely build all essential non-muscle actin-based cytoskeletal structures including mechanosensory stereocilia of hair cells that are necessary for hearing. Although [[gamma].sub.cyto]-actin-deficient stereocilia form normally, we found that they cannot maintain the integrity of the stereocilia actin core. In the wild-type, [[gamma].sub.cyto]-actin localizes along the length of stereocilia but re-distributes to sites of F-actin core disruptions resulting from animal exposure to damaging noise. In [Actg1.sup.-/-] stereocilia similar disruptions are observed even without noise exposure. We conclude that [[gamma].sub.cyto]-actin is required for reinforcement and long-term stability of F-actin-based structures but is not an essential building block of the developing cytoskeleton. actin | cytoskeleton | hearing

Published
2009

15. Angular Approach Scanning Ion Conductance Microscopy

Author

Shevchuk, Andrew, Tokar, Sergiy, Gopal, Sahana, Sanchez-Alonso, Jose L., Tarasov, Andrei I., Vélez-Ortega, A. Catalina, Chiappini, Ciro, Rorsman, Patrik, Stevens, Molly M., Gorelik, Julia, Frolenkov, Gregory I., Klenerman, David, Korchev, Yuri E., Wellcome Trust, and Biotechnology and Biological Sciences Research Council (BBSRC)

Subjects
Adult, Male, Patch-Clamp Techniques, 02 Physical Sciences, Biophysics, Equipment Design, Microscopy, Scanning Probe, 06 Biological Sciences, Culture Media, Rats, Sprague-Dawley, Mice, Micromanipulation, Imaging, Three-Dimensional, Cell Biophysics, Microscopy, Electron, Scanning, Animals, Humans, Nanotechnology, Female, 03 Chemical Sciences, Cells, Cultured, HeLa Cells
Abstract

Scanning ion conductance microscopy (SICM) is a super-resolution live imaging technique that uses a glass nanopipette as an imaging probe to produce three-dimensional (3D) images of cell surface. SICM can be used to analyze cell morphology at nanoscale, follow membrane dynamics, precisely position an imaging nanopipette close to a structure of interest, and use it to obtain ion channel recordings or locally apply stimuli or drugs. Practical implementations of these SICM advantages, however, are often complicated due to the limitations of currently available SICM systems that inherited their design from other scanning probe microscopes in which the scan assembly is placed right above the specimen. Such arrangement makes the setting of optimal illumination necessary for phase contrast or the use of high magnification upright optics difficult. Here, we describe the designs that allow mounting SICM scan head on a standard patch-clamp micromanipulator and imaging the sample at an adjustable approach angle. This angle could be as shallow as the approach angle of a patch-clamp pipette between a water immersion objective and the specimen. Using this angular approach SICM, we obtained topographical images of cells grown on nontransparent nanoneedle arrays, of islets of Langerhans, and of hippocampal neurons under upright optical microscope. We also imaged previously inaccessible areas of cells such as the side surfaces of the hair cell stereocilia and the intercalated disks of isolated cardiac myocytes, and performed targeted patch-clamp recordings from the latter. Thus, our new, to our knowledge, angular approach SICM allows imaging of living cells on nontransparent substrates and a seamless integration with most patch-clamp setups on either inverted or upright microscopes, which would facilitate research in cell biophysics and physiology.

Published
2016
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16. TRIOBP-5 sculpts stereocilia rootlets and stiffens supporting cells enabling hearing

Author

Katsuno, Tatsuya, primary, Belyantseva, Inna A., additional, Cartagena-Rivera, Alexander X., additional, Ohta, Keisuke, additional, Crump, Shawn M., additional, Petralia, Ronald S., additional, Ono, Kazuya, additional, Tona, Risa, additional, Imtiaz, Ayesha, additional, Rehman, Atteeq, additional, Kiyonari, Hiroshi, additional, Kaneko, Mari, additional, Wang, Ya-Xian, additional, Abe, Takaya, additional, Ikeya, Makoto, additional, Fenollar-Ferrer, Cristina, additional, Riordan, Gavin P., additional, Wilson, Elisabeth A., additional, Fitzgerald, Tracy S., additional, Segawa, Kohei, additional, Omori, Koichi, additional, Ito, Juichi, additional, Frolenkov, Gregory I., additional, Friedman, Thomas B., additional, and Kitajiri, Shin-ichiro, additional

Published
2019
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17. CIB2 interacts with TMC1 and TMC2 and is essential for mechanotransduction in auditory hair cells

Author

Giese, Arnaud P. J., primary, Tang, Yi-Quan, additional, Sinha, Ghanshyam P., additional, Bowl, Michael R., additional, Goldring, Adam C., additional, Parker, Andrew, additional, Freeman, Mary J., additional, Brown, Steve D. M., additional, Riazuddin, Saima, additional, Fettiplace, Robert, additional, Schafer, William R., additional, Frolenkov, Gregory I., additional, and Ahmed, Zubair M., additional

Published
2017
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20. Correction: A Novel C-Terminal CIB2 (Calcium and Integrin Binding Protein 2) Mutation Associated with Non-Syndromic Hearing Loss in a Hispanic Family

Author

Patel, Kunjan, primary, Giese, Arnaud P., additional, Grossheim, J. M., additional, Hegde, Rashmi S., additional, Delio, Maria, additional, Samanich, Joy, additional, Riazuddin, Saima, additional, Frolenkov, Gregory I., additional, Cai, Jinlu, additional, Ahmed, Zubair M., additional, and Morrow, Bernice E., additional

Published
2015
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21. RFX transcription factors are essential for hearing in mice

Author

Elkon, Ran, primary, Milon, Beatrice, additional, Morrison, Laura, additional, Shah, Manan, additional, Vijayakumar, Sarath, additional, Racherla, Manoj, additional, Leitch, Carmen C., additional, Silipino, Lorna, additional, Hadi, Shadan, additional, Weiss-Gayet, Michèle, additional, Barras, Emmanuèle, additional, Schmid, Christoph D., additional, Ait-Lounis, Aouatef, additional, Barnes, Ashley, additional, Song, Yang, additional, Eisenman, David J., additional, Eliyahu, Efrat, additional, Frolenkov, Gregory I., additional, Strome, Scott E., additional, Durand, Bénédicte, additional, Zaghloul, Norann A., additional, Jones, Sherri M., additional, Reith, Walter, additional, and Hertzano, Ronna, additional

Published
2015
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22. A Novel C-Terminal CIB2 (Calcium and Integrin Binding Protein 2) Mutation Associated with Non-Syndromic Hearing Loss in a Hispanic Family

Author

Patel, Kunjan, primary, Giese, Arnaud P., additional, Grossheim, J. M., additional, Hegde, Rashima S., additional, Delio, Maria, additional, Samanich, Joy, additional, Riazuddin, Saima, additional, Frolenkov, Gregory I., additional, Cai, Jinlu, additional, Ahmed, Zubair M., additional, and Morrow, Bernice E., additional

Published
2015
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24. Novel and recurrent CIB2 variants, associated with nonsyndromic deafness, do not affect calcium buffering and localization in hair cells

Author

Seco, Celia Zazo, primary, Giese, Arnaud P, additional, Shafique, Sobia, additional, Schraders, Margit, additional, Oonk, Anne M M, additional, Grossheim, Mike, additional, Oostrik, Jaap, additional, Strom, Tim, additional, Hegde, Rashmi, additional, van Wijk, Erwin, additional, Frolenkov, Gregory I, additional, Azam, Maleeha, additional, Yntema, Helger G, additional, Free, Rolien H, additional, Riazuddin, Saima, additional, Verheij, Joke B G M, additional, Admiraal, Ronald J, additional, Qamar, Raheel, additional, Ahmed, Zubair M, additional, and Kremer, Hannie, additional

Published
2015
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30. Actin-Bundling Protein TRIOBP Forms Resilient Rootlets of Hair Cell Stereocilia Essential for Hearing

Author

Kitajiri, Shin-ichiro, primary, Sakamoto, Takeshi, additional, Belyantseva, Inna A., additional, Goodyear, Richard J., additional, Stepanyan, Ruben, additional, Fujiwara, Ikuko, additional, Bird, Jonathan E., additional, Riazuddin, Saima, additional, Riazuddin, Sheikh, additional, Ahmed, Zubair M., additional, Hinshaw, Jenny E., additional, Sellers, James, additional, Bartles, James R., additional, Hammer, John A., additional, Richardson, Guy P., additional, Griffith, Andrew J., additional, Frolenkov, Gregory I., additional, and Friedman, Thomas B., additional

Published
2010
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31. Noncontact Measurement of the Local Mechanical Properties of Living Cells Using Pressure Applied via a Pipette

Author

Sánchez, Daniel, primary, Johnson, Nick, additional, Li, Chao, additional, Novak, Pavel, additional, Rheinlaender, Johannes, additional, Zhang, Yanjun, additional, Anand, Uma, additional, Anand, Praveen, additional, Gorelik, Julia, additional, Frolenkov, Gregory I., additional, Benham, Christopher, additional, Lab, Max, additional, Ostanin, Victor P., additional, Schäffer, Tilman E., additional, Klenerman, David, additional, and Korchev, Yuri E., additional

Published
2008
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32. Deafness and Stria Vascularis Defects in S1P2 Receptor-null Mice

Author

Kono, Mari, primary, Belyantseva, Inna A., additional, Skoura, Athanasia, additional, Frolenkov, Gregory I., additional, Starost, Matthew F., additional, Dreier, Jennifer L., additional, Lidington, Darcy, additional, Bolz, Steffen-Sebastian, additional, Friedman, Thomas B., additional, Hla, Timothy, additional, and Proia, Richard L., additional

Published
2007
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33. The 133-kDa N-terminal domain enables myosin 15 to maintain mechanotransducing stereocilia and is essential for hearing.

Author

Qing Fang, Indzhykulian, Artur A., Mustapha, Mirna, Riordan, Gavin P., Dolan, David F., Friedman, Thomas B., Belyantseva, Inna A., Frolenkov, Gregory I., Camper, Sally A., and Bird, Jonathan E.

Subjects
MYOSIN, HEARING, MECHANOTRANSDUCTION (Cytology)
Abstract

The article discusses a study which shows the significant role of myosin-15 isoforms in the maintenance of hair cell stereocilia assembly and critical for the sense of hearing.

Published
2015
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34. The Tip-Link Antigen, a Protein Associated with the Transduction Complex of Sensory Hair Cells, Is Protocadherin-15

Author

Ahmed, Zubair M., primary, Goodyear, Richard, additional, Riazuddin, Saima, additional, Lagziel, Ayala, additional, Legan, P. Kevin, additional, Behra, Martine, additional, Burgess, Shawn M., additional, Lilley, Kathryn S., additional, Wilcox, Edward R., additional, Riazuddin, Sheikh, additional, Griffith, Andrew J., additional, Frolenkov, Gregory I., additional, Belyantseva, Inna A., additional, Richardson, Guy P., additional, and Friedman, Thomas B., additional

Published
2006
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36. Novel and recurrent CIB2 variants, associated with nonsyndromic deafness, do not affect calcium buffering and localization in hair cells

Author

Seco, Celia Zazo, Giese, Arnaud P, Shafique, Sobia, Schraders, Margit, Oonk, Anne M M, Grossheim, Mike, Oostrik, Jaap, Strom, Tim, Hegde, Rashmi, van Wijk, Erwin, Frolenkov, Gregory I, Azam, Maleeha, Yntema, Helger G, Free, Rolien H, Riazuddin, Saima, Verheij, Joke B G M, Admiraal, Ronald J, Qamar, Raheel, Ahmed, Zubair M, and Kremer, Hannie

Abstract

Variants in CIB2 can underlie either Usher syndrome type I (USH1J) or nonsyndromic hearing impairment (NSHI) (DFNB48). Here, a novel homozygous missense variant c.196C>T and compound heterozygous variants, c.[97C>T];[196C>T], were found, respectively, in two unrelated families of Dutch origin. Besides, the previously reported c.272 T>C functional missense variant in CIB2 was identified in two families of Pakistani origin. The missense variants are demonstrated not to affect subcellular localization of CIB2 in vestibular hair cells in ex vivo expression experiments. Furthermore, these variants do not affect the ATP-induced calcium responses in COS-7 cells. However, based on the residues affected, the variants are suggested to alter αIIβ integrin binding. HI was nonsyndromic in all four families. However, deafness segregating with the c.272T>C variant in one Pakistani family is remarkably less severe than that in all other families with this mutation. Our results contribute to the insight in genotype–phenotype correlations of CIB2 mutations.

Published
2016
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42. An international comparison of long‐term average speech spectra

Author

Byrne, Denis, primary, Dillon, Harvey, additional, Tran, Khanh, additional, Arlinger, Stig, additional, Wilbraham, Keith, additional, Cox, Robyn, additional, Hagerman, Bjorn, additional, Hetu, Raymond, additional, Kei, Joseph, additional, Lui, C., additional, Kiessling, Jurgen, additional, Kotby, M. Nasser, additional, Nasser, Nasser H. A., additional, El Kholy, Wafaa A. H., additional, Nakanishi, Yasuko, additional, Oyer, Herbert, additional, Powell, Richard, additional, Stephens, Dafydd, additional, Meredith, Rhys, additional, Sirimanna, Tony, additional, Tavartkiladze, George, additional, Frolenkov, Gregory I., additional, Westerman, Soren, additional, and Ludvigsen, Carl, additional

Published
1994
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43. Fast Adaptation and Ca2+ Sensitivity of theMechanotransducer Require Myosin-XVa in Inner But Not Outer Cochlear Hair Cells.

Author

Stepanyan, Ruben and Frolenkov, Gregory I.

Subjects
*NEUROBIOLOGY, *TRANSDUCERS, *CHANNELS (Structural members), *HAIR cells, *COCHLEA, *MYOSIN, *LABORATORY mice
Abstract

In inner ear hair cells, activation of mechanotransduction channels is followed by extremely rapid deactivation that depends on the influx of Ca2+ through these channels. Although the molecular mechanisms of this "fast" adaptation are largely unknown, the predominant models assume Ca22+ sensitivity as an intrinsic property of yet unidentified mechanotransduction channels. Here, we examined mechanotransduction in the hair cells of young postnatal shaker 2 mice (Myo15sh2/sh2). These mice have no functional myosin-XVa, which is critical for normal growth of mechanosensory stereocilia of hair cells. Although stereocilia of both inner and outer hair cells of Myo15sh2/sh2 mice lack myosin-XVa and are abnormally short, these cells have dramatically different hair bundle morphology. Myo15sh2/sh2 outer hair cells retain a staircase arrangement of the abnormally short stereocilia and prominent tip links. Myo15sh2/sh2 inner hair cells do not have obliquely oriented tip links, and their mechanosensitivity is mediated exclusively by "top-to-top" links between equally short stereocilia. In both inner and outer hair cells of Myo15sh2/sh2 mice, we found mechanotransduction responses with a normal "wild-type" amplitude and speed of activation. Surprisingly, only outer hair cells exhibit fast adaptation and sensitivity to extracellular Ca22+. In Myo15sh2/sh2 inner hair cells, fast adaptation is disrupted and the transduction current is insensitive to extracellular Ca22+.We conclude that the Ca22+ sensitivity of the mechanotransduction channels and the fast adaptation require a structural environment that is dependent on myosin-XVa and is disrupted in Myo15sh2/sh2 inner hair cells, but not in Myo15sh2/sh2 outer hair cells. [ABSTRACT FROM AUTHOR]

Published
2009
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44. RFX transcription factors are essential for hearing in mice.

Author

Elkon, Ran, Milon, Beatrice, Morrison, Laura, Shah, Manan, Vijayakumar, Sarath, Racherla, Manoj, Leitch, Carmen C., Silipino, Lorna, Hadi, Shadan, Weiss-Gayet, Michèle, Barras, Emmanuèle, Schmid, Christoph D., Ait-Lounis, Aouatef, Barnes, Ashley, Song, Yang, Eisenman, David J., Eliyahu, Efrat, Frolenkov, Gregory I., Strome, Scott E., and Durand, Bénédicte

Subjects
DEAFNESS, HAIR cells, MECHANORECEPTORS, SENSORY receptors, KNOCKOUT mice
Abstract

Sensorineural hearing loss is a common and currently irreversible disorder, because mammalian hair cells (HCs) do not regenerate and current stem cell and gene delivery protocols result only in immature HC-like cells. Importantly, although the transcriptional regulators of embryonic HC development have been described, little is known about the postnatal regulators of maturating HCs. Here we apply a cell type-specific functional genomic analysis to the transcriptomes of auditory and vestibular sensory epithelia from early postnatal mice. We identify RFX transcription factors as essential and evolutionarily conserved regulators of the HC-specific transcriptomes, and detect Rfx1,2,3,5 and 7 in the developing HCs. To understand the role of RFX in hearing, we generate Rfx1/3 conditional knockout mice. We show that these mice are deaf secondary to rapid loss of initially well-formed outer HCs. These data identify an essential role for RFX in hearing and survival of the terminally differentiating outer HCs. [ABSTRACT FROM AUTHOR]

Published
2015
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45. Imaging analysis reveals budding of filamentous human metapneumovirus virions and direct transfer of inclusion bodies through intercellular extensions.

Author

El Najjar F, Castillo SR, Moncman CL, Wu C-Y, Isla E, Velez Ortega AC, Frolenkov GI, Cifuentes-Munoz N, and Dutch RE

Subjects
Humans, Aged, Cell Line, Cytoskeleton, Inclusion Bodies, Virion, Metapneumovirus
Abstract

Importance: Human metapneumovirus is an important respiratory pathogen that causes significant morbidity and mortality, particularly in the very young, the elderly, and the immunosuppressed. However, the molecular details of how this virus spreads to new target cells are unclear. This work provides important new information on the formation of filamentous structures that are consistent with virus particles and adds critical new insight into the structure of extensions between cells that form during infection. In addition, it demonstrates for the first time the movement of viral replication centers through these intercellular extensions, representing a new mode of direct cell-to-cell spread that may be applicable to other viral systems., Competing Interests: The authors declare no conflict of interest.

Published
2023
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46. Fast adaptation and Ca2+ sensitivity of the mechanotransducer require myosin-XVa in inner but not outer cochlear hair cells.

Author

Stepanyan R and Frolenkov GI

Subjects
Adaptation, Physiological genetics, Animals, Animals, Newborn, Biophysical Phenomena, Biophysics methods, Dose-Response Relationship, Drug, Hair Cells, Auditory, Inner ultrastructure, Hair Cells, Auditory, Outer drug effects, Hair Cells, Auditory, Outer physiology, Hair Cells, Auditory, Outer ultrastructure, Mechanotransduction, Cellular drug effects, Mechanotransduction, Cellular genetics, Membrane Potentials drug effects, Membrane Potentials genetics, Mice, Mice, Transgenic, Microscopy, Electron, Scanning methods, Mutation physiology, Myosins genetics, Organ Culture Techniques, Patch-Clamp Techniques methods, Physical Stimulation methods, Adaptation, Physiological physiology, Calcium pharmacology, Hair Cells, Auditory, Inner drug effects, Hair Cells, Auditory, Inner physiology, Mechanotransduction, Cellular physiology, Myosins physiology, Organ of Corti cytology
Abstract

In inner ear hair cells, activation of mechanotransduction channels is followed by extremely rapid deactivation that depends on the influx of Ca(2+) through these channels. Although the molecular mechanisms of this "fast" adaptation are largely unknown, the predominant models assume Ca(2+) sensitivity as an intrinsic property of yet unidentified mechanotransduction channels. Here, we examined mechanotransduction in the hair cells of young postnatal shaker 2 mice (Myo15(sh2/sh2)). These mice have no functional myosin-XVa, which is critical for normal growth of mechanosensory stereocilia of hair cells. Although stereocilia of both inner and outer hair cells of Myo15(sh2/sh2) mice lack myosin-XVa and are abnormally short, these cells have dramatically different hair bundle morphology. Myo15(sh2/sh2) outer hair cells retain a staircase arrangement of the abnormally short stereocilia and prominent tip links. Myo15(sh2/sh2) inner hair cells do not have obliquely oriented tip links, and their mechanosensitivity is mediated exclusively by "top-to-top" links between equally short stereocilia. In both inner and outer hair cells of Myo15(sh2/sh2) mice, we found mechanotransduction responses with a normal "wild-type" amplitude and speed of activation. Surprisingly, only outer hair cells exhibit fast adaptation and sensitivity to extracellular Ca(2+). In Myo15(sh2/sh2) inner hair cells, fast adaptation is disrupted and the transduction current is insensitive to extracellular Ca(2+). We conclude that the Ca(2+) sensitivity of the mechanotransduction channels and the fast adaptation require a structural environment that is dependent on myosin-XVa and is disrupted in Myo15(sh2/sh2) inner hair cells, but not in Myo15(sh2/sh2) outer hair cells.

Published
2009
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