Clustered Ca2+ Channels Are Blocked by Synaptic Vesicle Proton Release at Mammalian Auditory Ribbon Synapses
Clustered Ca2+ Channels Are Blocked by Synaptic Vesicle Proton Release at Mammalian Auditory Ribbon Synapses
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DOI：
10.1016/j.celrep.2018.11.072
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发表时间：
2018-12-18
期刊：
影响因子：
8.8
通讯作者：
Dulon, Didier
中科院分区：
文献类型：
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作者：
Vincent, Philippe F. Y.;Cho, Soyoun;Dulon, Didier
胞吐后，在一些带状突触中发生质子Ca2+电流瞬时阻断（ICaTB），但在哺乳动物毛细胞中尚未观察到这一现象。在这里，我们发现强大的ICaTB发生在听力后小鼠和沙鼠的内毛细胞（IHC）突触中，但不发生在未成熟的IHC突触中，后者包含非紧凑的活性区，其中Ca2+通道松散地偶联到释放位点。与其他带状突触中的ICaTB不同，哺乳动物ihc中的ICaTB显示出令人惊讶的多峰结构，这反映了配对记录中看到的epsc。与细胞内BAPTA解除囊泡释放同步或通过删除otoferlin（用于胞外分泌的Ca2+传感器）可大大降低ICaTB，而通过提高Ca2+内流或温度来增强释放同步可增加ICaTB。这表明ICaTB是由快速的多泡质子释放事件产生的。我们认为ICaTB可能是一种亚毫秒反馈机制，有助于听觉神经在声音刺激下的快速尖峰适应。
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 protonrelease events. We propose that ICaTB may function as a submillisecond feedback mechanism contributing to the auditory nerve's fast spike adaptation during sound stimulation.