{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T19:49:34Z","timestamp":1792698574119,"version":"4.5.0"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T00:00:00Z","timestamp":1732492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Mammalian hearing depends on the dual mechanosensory and motor functions of cochlear hair cells. Both these functions may be regulated by Ca<jats:sup>2+<\/jats:sup> release from intracellular stores. However, it is still unclear how exactly intracellular Ca<jats:sup>2+<\/jats:sup> release may affect either hair cell mechano-electrical transduction (MET) or prestin-dependent electromotility in outer hair cells (OHCs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here, we used photo-activatable (caged) compounds to generate fast increases of either Ca<jats:sup>2+<\/jats:sup> or inositol-3-phosphate (IP<jats:sub>3<\/jats:sub>) in the cytosol of young postnatal rodent auditory hair cells, thereby stimulating either Ca<jats:sup>2+<\/jats:sup>- or IP<jats:sub>3<\/jats:sub>- induced releases of Ca<jats:sup>2+<\/jats:sup> from intracellular stores. Fast Ca<jats:sup>2+<\/jats:sup> imaging was used to monitor propagation of Ca<jats:sup>2+<\/jats:sup> signals along the length of a hair cell. To access potential physiological role(s) of intracellular Ca<jats:sup>2+<\/jats:sup> releases, we used whole cell patch clamp to record: i) OHC voltage-dependent capacitance, a known electrical correlate of prestin-based electromotility, and ii) MET currents evoked by stereocilia bundle deflections with fluid-jet. In the latter experiments, changes of mechanical stiffness of the hair bundles were also quantified from video recordings of stereocilia movements.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Ca<jats:sup>2+<\/jats:sup> uncaging at the OHC apex initiated Ca<jats:sup>2+<\/jats:sup> wave propagating to the base of the cell with subsequent Ca<jats:sup>2+<\/jats:sup> build-up there. Ca<jats:sup>2+<\/jats:sup> uncaging at the OHC base generated long-lasting and apparently self-sustained Ca<jats:sup>2+<\/jats:sup> responses, further confirming Ca<jats:sup>2+<\/jats:sup>-induced Ca<jats:sup>2+<\/jats:sup> release in the OHC basal region. Photoactivated IP<jats:sub>3<\/jats:sub> initiated a slow increase of cytosolic Ca<jats:sup>2+<\/jats:sup> ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub><jats:italic>i<\/jats:italic><\/jats:sub>) throughout the whole OHC, confirming the presence of slow-activated IP<jats:sub>3<\/jats:sub>-gated Ca<jats:sup>2+<\/jats:sup> stores in OHCs. Interestingly, Ca<jats:sup>2+<\/jats:sup> uncaging produced no effects on OHC voltage-dependent capacitance. In an OHC, the rise of [Ca<jats:sup>2+<\/jats:sup>]<jats:sub><jats:italic>i<\/jats:italic><\/jats:sub> is known to decrease axial stiffness of the cell and may modulate the stiffness of mechanosensory stereocilia bundles. To separate these two phenomena, we explored the potential effects of intracellular Ca<jats:sup>2+<\/jats:sup> release on mechanical properties of stereocilia bundles in cochlear inner hair cells (IHCs). Ca<jats:sup>2+<\/jats:sup> uncaging at the apex of an IHC caused a long-lasting increase in mechanical stiffness of stereocilia bundle without any changes in the amplitude or deflection sensitivity of the MET current.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>We concluded that the most likely physiological role of IP<jats:sub>3<\/jats:sub>-gated Ca<jats:sup>2+<\/jats:sup> release at the apex of the cell is the regulation of hair bundle stiffness. In contrast, Ca<jats:sup>2+<\/jats:sup>-induced Ca<jats:sup>2+<\/jats:sup> release at the base of OHCs seems to regulate axial stiffness of the cells and its hyperpolarization in response to efferent stimuli, without direct effects on the OHC prestin-based membrane motors.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fncel.2024.1484998","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T04:27:14Z","timestamp":1732508834000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Regulation of cochlear hair cell function by intracellular calcium stores"],"prefix":"10.3389","volume":"18","author":[{"given":"Ghanshyam P.","family":"Sinha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory I.","family":"Frolenkov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,11,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-24-j0002.2000","article-title":"Expression and localization of prestin and the sugar transporter Glut-5 during development of electromotility in cochlear outer hair cells.","volume":"20","author":"Belyantseva","year":"2000","journal-title":"J. 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