Clustered Ca2+ Channels Are Blocked by Synaptic Vesicle Proton Release at Mammalian Auditory Ribbon Synapses

Philippe F.Y. Vincent, Soyoun Cho, Margot Tertrais, Yohan Bouleau, Henrique von Gersdorff, Didier Dulon

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3451-3464.e3
JournalCell Reports
Volume25
Issue number12
DOIs
StatePublished - Dec 18 2018

Keywords

  • Ca channels
  • auditory nerve fiber
  • exocytosis
  • inner hair cells
  • otoferlin
  • pH buffering
  • protons
  • ribbon synapses

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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