First Author | Vincent PFY | Year | 2018 |
Journal | Cell Rep | Volume | 25 |
Issue | 12 | Pages | 3451-3464.e3 |
PubMed ID | 30566869 | Mgi Jnum | J:270761 |
Mgi Id | MGI:6278697 | Doi | 10.1016/j.celrep.2018.11.072 |
Citation | Vincent PFY, et al. (2018) Clustered Ca(2+) Channels Are Blocked by Synaptic Vesicle Proton Release at Mammalian Auditory Ribbon Synapses. Cell Rep 25(12):3451-3464.e3 |
abstractText | A Ca(2+) 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 Ca(2+) 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 Ca(2+) sensor for exocytosis, greatly reduces ICaTB, whereas enhancing release synchronization by raising Ca(2+) 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. |