| First Author | Dulon D | Year | 2009 |
| Journal | J Neurosci | Volume | 29 |
| Issue | 34 | Pages | 10474-87 |
| PubMed ID | 19710301 | Mgi Jnum | J:152316 |
| Mgi Id | MGI:4358006 | Doi | 10.1523/JNEUROSCI.1009-09.2009 |
| Citation | Dulon D, et al. (2009) Otoferlin is critical for a highly sensitive and linear calcium-dependent exocytosis at vestibular hair cell ribbon synapses. J Neurosci 29(34):10474-87 |
| abstractText | 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. |
