TY - JOUR T1 - Few Ca<sub>V</sub>1.3 Channels Regulate the Exocytosis of a Synaptic Vesicle at the Hair Cell Ribbon Synapse JF - The Journal of Neuroscience JO - J. Neurosci. SP - 11577 LP - 11585 DO - 10.1523/JNEUROSCI.3411-05.2005 VL - 25 IS - 50 AU - Andreas Brandt AU - Darina Khimich AU - Tobias Moser Y1 - 2005/12/14 UR - http://www.jneurosci.org/content/25/50/11577.abstract N2 - Hearing relies on faithful sound coding at hair cell ribbon synapses, which use Ca2+-triggered glutamate release to signal with submillisecond precision. Here, we investigated stimulus–secretion coupling at mammalian inner hair cell (IHC) synapses to explore the mechanisms underlying this high temporal fidelity. Using nonstationary fluctuation analysis on Ca2+ tail currents, we estimate that IHCs contain ∼1700 Ca2+ channels, mainly of CaV1.3 type. We show by immunohistochemistry that the CaV1.3 Ca2+ channels are localized preferentially at the ribbon-type active zones of IHCs. We argue that each active zone holds ∼80 Ca2+ channels, of which probably &lt;10 open simultaneously during physiological stimulation. We then manipulated the Ca2+ current by primarily changing single-channel current or open-channel number. Effects on exocytosis of the readily releasable vesicle pool (RRP) were monitored by membrane capacitance recordings. Consistent with the high intrinsic Ca2+ cooperativity of exocytosis, RRP exocytosis changed nonlinearly with the Ca2+ current when varying the single-channel current. In contrast, the apparent Ca2+ cooperativity of RRP exocytosis was close to unity when primarily manipulating the number of open channels. Our findings suggest a Ca2+ channel–release site coupling in which few nearby CaV1.3 channels impose high nanodomain [Ca2+] on release sites in IHCs during physiological stimulation. We postulate that the IHC ribbon synapse uses this Ca2+ nanodomain control of exocytosis to signal with high temporal precision already at low sound intensities. ER -