Developmental refinement of hair cell synapses tightens the coupling of Ca2+ influx to exocytosis
Developmental refinement of hair cell synapses tightens the coupling of Ca2+ influx to exocytosis
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DOI：
10.1002/embj.201387110
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发表时间：
2014-02
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影响因子：
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通讯作者：
A. Wong;M. Rutherford;Mantas Gabrielaitis;T. Pangršič;F. Göttfert;Thomas Frank;Susann Michanski;S. Hell;F. Wolf;C. Wichmann;T. Moser
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作者：
A. Wong;M. Rutherford;Mantas Gabrielaitis;T. Pangršič;F. Göttfert;Thomas Frank;Susann Michanski;S. Hell;F. Wolf;C. Wichmann;T. Moser
耳蜗内毛细胞（IHC）从感觉前起搏器发展到声音换能器。在这里，我们报告说，这涉及的结构和功能的变化之间的带状突触的IHC和螺旋神经节神经元（SGNs）周围的小鼠听力发作。随着突触的成熟，它们从保持几个小的突触前活动区（AZ）和并列的突触后密度（PSD）变为每个SGN终扣一个大的AZ/PSD复合体。在听力开始后，（i）IHC具有更少和更大的条带;（ii）CaV1.3通道形成条纹状簇，而不是未成熟AZ的较小和圆形簇;（iii）突触外CaV1.3通道选择性减少，（iv）通过Ca 2+释放探测的快速胞吐的内在Ca 2+依赖性保持不变，但（v）胞吐的表观Ca 2+依赖性线性化，当通过渐进式二氢吡啶阻断Ca 2+内流来评估时。在成熟和不成熟的AZ地形的胞吐的生物物理模型表明，通过一个单独的通道内流的Ca 2+占主导地位的[Ca 2 +]驱动胞吐在每个成熟的释放网站。我们的结论是，IHC突触进行重大的发展完善，导致更紧密的空间耦合之间的Ca 2+流入和胞吐。
Cochlear inner hair cells (IHCs) develop from pre‐sensory pacemaker to sound transducer. Here, we report that this involves changes in structure and function of the ribbon synapses between IHCs and spiral ganglion neurons (SGNs) around hearing onset in mice. As synapses matured they changed from holding several small presynaptic active zones (AZs) and apposed postsynaptic densities (PSDs) to one large AZ/PSD complex per SGN bouton. After the onset of hearing (i) IHCs had fewer and larger ribbons; (ii) CaV1.3 channels formed stripe‐like clusters rather than the smaller and round clusters at immature AZs; (iii) extrasynaptic CaV1.3‐channels were selectively reduced, (iv) the intrinsic Ca2+ dependence of fast exocytosis probed by Ca2+ uncaging remained unchanged but (v) the apparent Ca2+ dependence of exocytosis linearized, when assessed by progressive dihydropyridine block of Ca2+ influx. Biophysical modeling of exocytosis at mature and immature AZ topographies suggests that Ca2+ influx through an individual channel dominates the [Ca2+] driving exocytosis at each mature release site. We conclude that IHC synapses undergo major developmental refinements, resulting in tighter spatial coupling between Ca2+ influx and exocytosis.