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To investigate the biophysical properties of the synaptic machinery, we measured changes in membrane capacitance (\u0394<jats:italic>C<\/jats:italic><jats:sub>m<\/jats:sub>) in low-frequency (apical region, \u223c300 Hz) and high-frequency (basal, \u223c30 kHz) gerbil IHCs maintained in near physiological conditions (1.3 m<jats:sc>m<\/jats:sc>extracellular Ca<jats:sup>2+<\/jats:sup>and body temperature). With maturation, the Ca<jats:sup>2+<\/jats:sup>efficiency of exocytosis improved in both apical and basal IHCs and was more pronounced in the latter. Prehearing IHCs showed a similar Ca<jats:sup>2+<\/jats:sup>cooperativity of exocytosis despite the smaller \u0394<jats:italic>C<\/jats:italic><jats:sub>m<\/jats:sub>in apical cells. After maturation, \u0394<jats:italic>C<\/jats:italic><jats:sub>m<\/jats:sub>in high-frequency IHCs increased linearly with the Ca<jats:sup>2+<\/jats:sup>current, whereas, somewhat surprisingly, the relationship was significantly more nonlinear in low-frequency cells. This tonotopic difference seemed to be correlated with ribbon synapse morphology (spherical in apical and ellipsoid in basal IHCs) but not with the expression level of the proposed Ca<jats:sup>2+<\/jats:sup>sensor otoferlin or the spatial coupling between Ca<jats:sup>2+<\/jats:sup>channels and active zones. Repetitive stimulation of adult IHCs showed that vesicle pool refilling could become rate limiting for vesicle release, with high-frequency IHCs able to sustain greater release rates. Together, our findings provide the first evidence for a tonotopic difference in the properties of the synaptic machinery in mammalian IHCs, which could be essential for fine-tuning their receptor characteristics during sound stimulation.<\/jats:p>","DOI":"10.1523\/jneurosci.0785-08.2008","type":"journal-article","created":{"date-parts":[[2008,7,23]],"date-time":"2008-07-23T16:28:29Z","timestamp":1216830509000},"page":"7670-7678","source":"Crossref","is-referenced-by-count":106,"title":["Tonotopic Variation in the Calcium Dependence of Neurotransmitter Release and Vesicle Pool Replenishment at Mammalian Auditory Ribbon Synapses"],"prefix":"10.1523","volume":"28","author":[{"given":"Stuart 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