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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,12,5]]},"abstract":"<jats:p>\n                    In our hearing organ, sound is encoded at ribbon synapses formed by inner hair cells (IHCs) and spiral ganglion neurons (SGNs). How the underlying synaptic vesicle (SV) release is controlled by Ca\n                    <jats:sup>2+<\/jats:sup>\n                    in IHCs of hearing animals remained to be investigated. Here, we performed patch-clamp SGN recordings of the initial rate of release evoked by brief IHC Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -influx in an ex vivo cochlear preparation from hearing mice. We aimed to closely mimic physiological conditions by perforated-patch recordings from IHCs kept at the physiological resting potential and at body temperature. We found release to relate supralinearly to Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -influx (power,\n                    <jats:italic>m<\/jats:italic>\n                    : 4.3) when manipulating the [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ] available for SV release by Zn\n                    <jats:sup>2+<\/jats:sup>\n                    -flicker-blocking of the single Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -channel current. In contrast, a near linear Ca\n                    <jats:sup>2+<\/jats:sup>\n                    dependence (\n                    <jats:italic>m<\/jats:italic>\n                    : 1.2 to 1.5) was observed when varying the number of open Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -channels during deactivating Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -currents and by dihydropyridine channel-inhibition. Concurrent changes of number and current of open Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -channels over the range of physiological depolarizations revealed\n                    <jats:italic>m<\/jats:italic>\n                    : 1.8. These findings indicate that SV release requires ~4 Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -ions to bind to their Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -sensor of fusion. We interpret the near linear Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -dependence of release during manipulations that change the number of open Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -channels to reflect control of SV release by the high [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ] in the Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -nanodomain of one or few nearby Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -channels. We propose that a combination of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    nanodomain control and supralinear intrinsic Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -dependence of fusion optimally links SV release to the timing and amplitude of the IHC receptor potential and separates it from other IHC Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -signals unrelated to afferent synaptic transmission.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2311539120","type":"journal-article","created":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T13:37:58Z","timestamp":1701265078000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":27,"title":["Ca\n                    <sup>2+<\/sup>\n                    regulation of glutamate release from inner hair cells of hearing mice"],"prefix":"10.1073","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6752-7750","authenticated-orcid":false,"given":"Lina Mar\u00eda","family":"Jaime Tob\u00f3n","sequence":"first","affiliation":[{"name":"Auditory Neuroscience and Synaptic Nanophysiology Group, Max Planck Institute for Multidisciplinary Sciences, G\u00f6ttingen 37077, Germany"},{"name":"Institute for Auditory Neuroscience, University Medical Center G\u00f6ttingen, G\u00f6ttingen 37075, Germany"},{"name":"Collaborative Research Center 889, University of G\u00f6ttingen, G\u00f6ttingen 37075, Germany"},{"name":"Multiscale Bioimaging of Excitable Cells, Cluster of Excellence, G\u00f6ttingen 37075, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7145-0533","authenticated-orcid":false,"given":"Tobias","family":"Moser","sequence":"additional","affiliation":[{"name":"Auditory Neuroscience and Synaptic Nanophysiology Group, Max Planck Institute for Multidisciplinary Sciences, G\u00f6ttingen 37077, Germany"},{"name":"Institute for Auditory Neuroscience, University Medical Center G\u00f6ttingen, G\u00f6ttingen 37075, Germany"},{"name":"Collaborative Research Center 889, University of G\u00f6ttingen, G\u00f6ttingen 37075, Germany"},{"name":"Multiscale Bioimaging of Excitable Cells, Cluster of Excellence, G\u00f6ttingen 37075, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2023,11,29]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00026.2018"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1113\/JP279189"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1983.sp014668"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108551"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903010309"},{"key":"e_1_3_4_6_2","volume-title":"Discharge Patterns of Single Fibers in the Cat\u2019s Auditory Nerve","author":"Kiang N. 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