Calcium- and otoferlin-dependent exocytosis by immature outer hair cells.

M. Beurg, S. Safieddine, I. Roux, Y. Bouleau, C. Petit, D. Dulon
Journal of Neuroscience. 2008-02-20; 28(8): 1798-1803
DOI: 10.1523/jneurosci.4653-07.2008

Lire sur PubMed

1. J Neurosci. 2008 Feb 20;28(8):1798-803. doi: 10.1523/JNEUROSCI.4653-07.2008.

Calcium- and otoferlin-dependent exocytosis by immature outer hair cells.

Beurg M(1), Safieddine S, Roux I, Bouleau Y, Petit C, Dulon D.

Author information:
(1)Equipe Neurophysiologie de la Synapse Auditive, Inserm U587 et Université
Victor Segalen, Institut des Neurosciences de Bordeaux, Centre Hospitalier
Universitaire Pellegrin, 33076 Bordeaux, France.

Immature cochlear outer hair cells (OHCs) make transient synaptic contacts
(ribbon synapses) with type I afferent nerve fibers, but direct evidence of
synaptic vesicle exocytosis is still missing. We thus investigated
calcium-dependent exocytosis in murine OHCs at postnatal day 2 (P2)-P3, a
developmental stage when calcium current maximum amplitude was the highest. By
using time-resolved patch-clamp capacitance measurements, we show that voltage
step activation of L-type calcium channels triggers fast membrane capacitance
increase. Capacitance increase displayed two kinetic components, which are likely
to reflect two functionally distinct pools of synaptic vesicles, a readily
releasable pool (RRP; tau = 79 ms) and a slowly releasable pool (tau = 870 ms).
The RRP size and maximal release rate were estimated at approximately 1200
vesicles and approximately 15,000 vesicles/s, respectively. In addition, we found
a linear relationship between capacitance increase and calcium influx, like in
mature inner hair cells (IHCs). These results give strong support to the
existence of efficient calcium-dependent neurotransmitter release in immature
OHCs. Moreover, we show that immature OHCs, just like immature IHCs, are able to
produce regenerative calcium-dependent action potentials that could trigger
synaptic exocytosis in vivo. Finally, the evoked membrane capacitance increases
were abolished in P2-P3 OHCs from mutant Otof-/- mice defective for otoferlin,
despite normal calcium currents. We conclude that otoferlin, the putative major
calcium sensor at IHC ribbon synapses, is essential to synaptic exocytosis in
immature OHCs too.

DOI: 10.1523/JNEUROSCI.4653-07.2008
PMID: 18287496 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus