@article{ee265f8e3c214d7e84b0721d441debe6,
title = "Clustered Ca2+ Channels Are Blocked by Synaptic Vesicle Proton Release at Mammalian Auditory Ribbon Synapses",
abstract = "A Ca2+ current transient block (ICaTB) by protons occurs at some ribbon-type synapses after exocytosis, but this has not been observed at mammalian hair cells. Here we show that a robust ICaTB occurs at post-hearing mouse and gerbil inner hair cell (IHC) synapses, but not in immature IHC synapses, which contain non-compact active zones, where Ca2+ channels are loosely coupled to the release sites. Unlike ICaTB at other ribbon synapses, ICaTB in mammalian IHCs displays a surprising multi-peak structure that mirrors the EPSCs seen in paired recordings. Desynchronizing vesicular release with intracellular BAPTA or by deleting otoferlin, the Ca2+ sensor for exocytosis, greatly reduces ICaTB, whereas enhancing release synchronization by raising Ca2+ influx or temperature increases ICaTB. This suggests that ICaTB is produced by fast multivesicular proton-release events. We propose that ICaTB may function as a submillisecond feedback mechanism contributing to the auditory nerve's fast spike adaptation during sound stimulation.",
keywords = "Ca channels, auditory nerve fiber, exocytosis, inner hair cells, otoferlin, pH buffering, protons, ribbon synapses",
author = "Vincent, {Philippe F.Y.} and Soyoun Cho and Margot Tertrais and Yohan Bouleau and {von Gersdorff}, Henrique and Didier Dulon",
note = "Funding Information: This work was supported in part by grants from Fondation Pour l'Audition (to D.D.) and grants from the National Institute on Deafness and Other Communication Disorders (NIDCD) (R01 DC004274 and R01 DC012938 to H.v.G.). We thank Christine Petit for helpful discussions, as well as Brad Buran and M. Charles Liberman for their helpful advice and discussions on the mouse auditory single fiber recordings. We thank Robert Renden for discussions and recordings from the calyx of Held synapse and the Bordeaux Imaging Center, where the confocal microscopy was performed. Funding Information: This work was supported in part by grants from Fondation Pour l{\textquoteright}Audition (to D.D.) and grants from the National Institute on Deafness and Other Communication Disorders (NIDCD) ( R01 DC004274 and R01 DC012938 to H.v.G.). We thank Christine Petit for helpful discussions, as well as Brad Buran and M. Charles Liberman for their helpful advice and discussions on the mouse auditory single fiber recordings. We thank Robert Renden for discussions and recordings from the calyx of Held synapse and the Bordeaux Imaging Center, where the confocal microscopy was performed. Publisher Copyright: {\textcopyright} 2018",
year = "2018",
month = dec,
day = "18",
doi = "10.1016/j.celrep.2018.11.072",
language = "English (US)",
volume = "25",
pages = "3451--3464.e3",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "12",
}