Otoferlin is critical for a highly sensitive and linear calcium-dependent exocytosis at vestibular hair cell ribbon synapses

Didier Dulon, Saaid Safieddine, Sherri M. Jones, Christine Petit

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

Otoferlin, a C2-domain-containing Ca2+ 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 Ca2+ entry, flowing through voltage-activatedCa2+channels,andexocytosis. This linearCa2+dependencewasobservedwhenchanging theCa 2+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 nonlinear 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.

Original languageEnglish (US)
Pages (from-to)10474-10487
Number of pages14
JournalJournal of Neuroscience
Volume29
Issue number34
DOIs
StatePublished - Aug 26 2009

Fingerprint

Vestibular Hair Cells
Exocytosis
Synapses
Calcium
Auditory Hair Cells
Vestibular Nerve
Saccule and Utricle
Architectural Accessibility
Action Potentials
Carrier Proteins

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Otoferlin is critical for a highly sensitive and linear calcium-dependent exocytosis at vestibular hair cell ribbon synapses. / Dulon, Didier; Safieddine, Saaid; Jones, Sherri M.; Petit, Christine.

In: Journal of Neuroscience, Vol. 29, No. 34, 26.08.2009, p. 10474-10487.

Research output: Contribution to journalArticle

@article{29d8592c5ce24dfd9f01d74958a2e696,
title = "Otoferlin is critical for a highly sensitive and linear calcium-dependent exocytosis at vestibular hair cell ribbon synapses",
abstract = "Otoferlin, a C2-domain-containing Ca2+ 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 Ca2+ entry, flowing through voltage-activatedCa2+channels,andexocytosis. This linearCa2+dependencewasobservedwhenchanging theCa 2+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 nonlinear 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.",
author = "Didier Dulon and Saaid Safieddine and Jones, {Sherri M.} and Christine Petit",
year = "2009",
month = "8",
day = "26",
doi = "10.1523/JNEUROSCI.1009-09.2009",
language = "English (US)",
volume = "29",
pages = "10474--10487",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "34",

}

TY - JOUR

T1 - Otoferlin is critical for a highly sensitive and linear calcium-dependent exocytosis at vestibular hair cell ribbon synapses

AU - Dulon, Didier

AU - Safieddine, Saaid

AU - Jones, Sherri M.

AU - Petit, Christine

PY - 2009/8/26

Y1 - 2009/8/26

N2 - Otoferlin, a C2-domain-containing Ca2+ 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 Ca2+ entry, flowing through voltage-activatedCa2+channels,andexocytosis. This linearCa2+dependencewasobservedwhenchanging theCa 2+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 nonlinear 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.

AB - Otoferlin, a C2-domain-containing Ca2+ 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 Ca2+ entry, flowing through voltage-activatedCa2+channels,andexocytosis. This linearCa2+dependencewasobservedwhenchanging theCa 2+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 nonlinear 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.

UR - http://www.scopus.com/inward/record.url?scp=69449092161&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=69449092161&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.1009-09.2009

DO - 10.1523/JNEUROSCI.1009-09.2009

M3 - Article

C2 - 19710301

AN - SCOPUS:69449092161

VL - 29

SP - 10474

EP - 10487

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 34

ER -