Otoferlin is critical for a highly sensitive and linear calcium-dependent exocytosis at vestibular hair cell ribbon synapses.
Otoferlin is critical for a highly sensitive and linear calcium-dependent exocytosis at vestibular hair cell ribbon synapses.
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DOI：
10.1523/jneurosci.1009-09.2009
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发表时间：
2009-08-26
期刊：
影响因子：
--
通讯作者：
Petit C
中科院分区：
文献类型：
--
作者：
Dulon D;Safieddine S;Jones SM;Petit C
Otoferlin, a C2-domain containing Ca2+ binding protein, is required for synaptic exocytosis in auditory hair cells. However, its exact role remains largely unknown. Intriguingly enough, no balance defect has been observed in otoferlin-deficient (Otof−/−) mice. Here, we show that the vestibular nerve compound action potentials evoked during transient linear acceleration ramps in Otof−/− mice display higher threshold, lower amplitude and increased latency compared to wild-type mice. Using patch clamp capacitance measurement in intact utricles, we show that type I and type II hair cells display a remarkable linear transfer function between Ca2+ entry, flowing through voltage-activated Ca2+ channels, and exocytosis. This linear Ca2+ dependence was observed when changing the Ca2+ channel open probability or the Ca2+ flux per channel during various test potentials. In Otof−/− hair cells, exocytosis displays slower kinetics, reduced Ca2+ sensitivity and non-linear Ca2+ dependence, despite morphologically normal synapses and normal Ca2+ currents. We conclude that otoferlin is essential for a high affinity Ca2+ sensor function that allows efficient and linear encoding of low intensity stimuli at the vestibular hair cell synapse.
