Exocytotic machineries of vestibular type I and cochlear ribbon synapses display similar intrinsic otoferlin-dependent Ca2+ sensitivity but a different coupling to Ca2+ channels.
Journal of Neuroscience. 2014-08-13; 34(33): 10853-10869
DOI: 10.1523/jneurosci.0947-14.2014
Read on PubMed
1. J Neurosci. 2014 Aug 13;34(33):10853-69. doi: 10.1523/JNEUROSCI.0947-14.2014.
Exocytotic machineries of vestibular type I and cochlear ribbon synapses display
similar intrinsic otoferlin-dependent Ca2+ sensitivity but a different coupling
to Ca2+ channels.
Vincent PF(1), Bouleau Y(2), Safieddine S(3), Petit C(4), Dulon D(1).
Author information:
(1)Université de Bordeaux, Institut des Neurosciences de Bordeaux, Equipe
Neurophysiologie de la Synapse Auditive, Inserm, Unité Mixte de Recherche 1120,
Centre Hospitalier Universitaire hôpital Pellegrin, 33076 Bordeaux, France,
.
(2)Université de Bordeaux, Institut des Neurosciences de Bordeaux, Equipe
Neurophysiologie de la Synapse Auditive, Inserm, Unité Mixte de Recherche 1120,
Centre Hospitalier Universitaire hôpital Pellegrin, 33076 Bordeaux, France.
(3)Institut Pasteur et Université Pierre et Marie Curie, Unité de Génétique et
Physiologie de l’Audition, Inserm Unité Mixte de Recherche 1120, 75015 Paris,
France, and.
(4)Institut Pasteur et Université Pierre et Marie Curie, Unité de Génétique et
Physiologie de l’Audition, Inserm Unité Mixte de Recherche 1120, 75015 Paris,
France, and Collège de France, 75005 Paris, France.
The hair cell ribbon synapses of the mammalian auditory and vestibular systems
differ greatly in their anatomical organization and firing properties. Notably,
vestibular Type I hair cells (VHC-I) are surrounded by a single calyx-type
afferent terminal that receives input from several ribbons, whereas cochlear
inner hair cells (IHCs) are contacted by several individual afferent boutons,
each facing a single ribbon. The specificity of the presynaptic molecular
mechanisms regulating transmitter release at these different sensory ribbon
synapses is not well understood. Here, we found that exocytosis during voltage
activation of Ca(2+) channels displayed higher Ca(2+) sensitivity, 10 mV more
negative half-maximum activation, and a smaller dynamic range in VHC-I than in
IHCs. VHC-I had a larger number of Ca(2+) channels per ribbon (158 vs 110 in
IHCs), but their Ca(2+) current density was twofold smaller because of a smaller
open probability and unitary conductance. Using confocal and stimulated emission
depletion immunofluorescence microscopy, we showed that VHC-I had fewer synaptic
ribbons (7 vs 17 in IHCs) to which Cav1.3 channels are more tightly organized
than in IHCs. Gradual intracellular Ca(2+) uncaging experiments revealed that
exocytosis had a similar intrinsic Ca(2+) sensitivity in both VHC-I and IHCs (KD
of 3.3 ± 0.6 μM and 4.0 ± 0.7 μM, respectively). In otoferlin-deficient mice,
exocytosis was largely reduced in VHC-I and IHCs. We conclude that VHC-I and IHCs
use a similar micromolar-sensitive otoferlin Ca(2+) sensor and that their sensory
encoding specificity is essentially determined by a different functional
organization of Ca(2+) channels at their synaptic ribbons.
Copyright © 2014 the authors 0270-6474/14/3410853-17$15.00/0.
DOI: 10.1523/JNEUROSCI.0947-14.2014
PMID: 25122888 [Indexed for MEDLINE]