Otoferlin Is Critical for a Highly Sensitive and Linear Calcium-Dependent Exocytosis at Vestibular Hair Cell Ribbon Synapses - Archive ouverte HAL
Article Dans Une Revue (Data Paper) Journal of Neuroscience Année : 2009

Otoferlin Is Critical for a Highly Sensitive and Linear Calcium-Dependent Exocytosis at Vestibular Hair Cell Ribbon Synapses

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Otoferlin, a C2-domain-containing Ca 2+ binding protein, is required for synaptic exocytosis in auditory hair cells. However, its exact role remains essentially 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 with 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 Ca 2+ entry, flowing through voltage-activated Ca 2+ channels, and exocytosis. This linear Ca 2+ dependence was observed when changing the Ca 2+ channel open probability or the Ca 2+ flux per channel during various test potentials. In Otof −/− hair cells, exocytosis displays slower kinetics, reduced Ca 2+ sensitivity, and nonlinear Ca 2+ dependence, despite morphologically normal synapses and normal Ca 2+ currents. We conclude that otoferlin is essential for a high-affinity Ca 2+ sensor function that allows efficient and linear encoding of low-intensity stimuli at the vestibular hair cell synapse.
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hal-04159603 , version 1 (12-07-2023)

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Didier Dulon, Saaid Safieddine, Sherri M Jones, Christine Petit. Otoferlin Is Critical for a Highly Sensitive and Linear Calcium-Dependent Exocytosis at Vestibular Hair Cell Ribbon Synapses. Journal of Neuroscience, 2009, 29 (34), pp.10474-10487. ⟨10.1523/JNEUROSCI.1009-09.2009⟩. ⟨hal-04159603⟩
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