Otoferlin is critical for a highly sensitive and linear calcium-dependent exocytosis at vestibular hair cell ribbon synapses.
Journal of Neuroscience. 2009-08-26; 29(34): 10474-10487
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1. J Neurosci. 2009 Aug 26;29(34):10474-87. doi: 10.1523/JNEUROSCI.1009-09.2009.
Otoferlin is critical for a highly sensitive and linear calcium-dependent
exocytosis at vestibular hair cell ribbon synapses.
Dulon D(1), Safieddine S, Jones SM, Petit C.
(1)Université Victor Segalen Bordeaux 2, Institut des Neurosciences de Bordeaux,
Equipe Neurophysiologie de la Synapse Auditive, Inserm, Unité Mixte de Recherche
en Santé 587, Centre Hospitalier Universitaire Hôpital Pellegrin, 33076 Bordeaux,
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.
PMID: 19710301 [Indexed for MEDLINE]