Mechanotransduction current is essential for stability of the transducing stereocilia in mammalian auditory hair cells
| Autor: | A. Catalina Vélez-Ortega, Gregory I. Frolenkov, Artur A. Indzhykulian, Jonathan M Grossheim, Mary J Freeman |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
hair cells Mouse QH301-705.5 Science chemistry.chemical_element Biology Calcium Mechanotransduction Cellular General Biochemistry Genetics and Molecular Biology Rats Sprague-Dawley Stereocilia 03 medical and health sciences deafness Hair Cells Auditory medicine otorhinolaryngologic diseases Animals Inner ear Biology (General) Mechanotransduction Actin mechanotransduction calcium General Immunology and Microbiology General Neuroscience General Medicine Anatomy Cell Biology Kinocilium Mice Inbred C57BL On cells 030104 developmental biology medicine.anatomical_structure chemistry Animals Newborn Biophysics Microscopy Electron Scanning Medicine Rat Hair cell sense organs actin Research Article Neuroscience |
| Zdroj: | eLife eLife, Vol 6 (2017) |
| ISSN: | 2050-084X |
| Popis: | Mechanotransducer channels at the tips of sensory stereocilia of inner ear hair cells are gated by the tension of 'tip links' interconnecting stereocilia. To ensure maximal sensitivity, tip links are tensioned at rest, resulting in a continuous influx of Ca2+ into the cell. Here, we show that this constitutive Ca2+ influx, usually considered as potentially deleterious for hair cells, is in fact essential for stereocilia stability. In the auditory hair cells of young postnatal mice and rats, a reduction in mechanotransducer current, via pharmacological channel blockers or disruption of tip links, leads to stereocilia shape changes and shortening. These effects occur only in stereocilia that harbor mechanotransducer channels, recover upon blocker washout or tip link regeneration and can be replicated by manipulations of extracellular Ca2+ or intracellular Ca2+ buffering. Thus, our data provide the first experimental evidence for the dynamic control of stereocilia morphology by the mechanotransduction current. DOI: http://dx.doi.org/10.7554/eLife.24661.001 eLife digest Our sense of hearing depends on cells known as hair cells that line the inner ear. Each hair cell has tiny projections called stereocilia, which are arranged in a bundle with rows of increasing height like a staircase and are connected to each other by tiny filaments called tip-links. When sound waves hit the stereocilia, the tension on the tip-links increases, which opens “mechanotransduction” channels on the shorter stereocilia that allow calcium ions to flow into the cells. To ensure that the ears can detect even the softest sounds, the tip-links always have a small amount of tension which allows a small, but continuous flow of calcium ions into the cell. Scientists generally consider this continuous flow of calcium ions as a potentially harmful byproduct of sensitive hearing. Vélez-Ortega et al. isolated inner ear tissues from young mice and rats and exposed them to drugs that either block the flow of calcium ions through the mechanotransduction channels or break the tip-links on stereocilia. Surprisingly, these drugs made profound changes in the shape of individual stereocilia and the staircase architecture of the stereocilia bundle. When the drugs were rinsed out of the hair cells, the stereocilia went back to their normal shape. Sequestering of free calcium ions inside the hair cells had a similar effect on the shape of stereocilia. These findings show that the flow of calcium ions into the sterocilia via mechanotransduction channels controls the exquisite staircase-like architecture of the stereocilia bundle. More research is needed to identify which structural proteins cause the stereocilia shape changes and to work out exactly how calcium ions are involved. DOI: http://dx.doi.org/10.7554/eLife.24661.002 |
| Databáze: | OpenAIRE |
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