Developmental acquisition of a rapid calcium-regulated vesicle supply allows sustained high rates of exocytosis in auditory hair cells.
PLoS ONE. 2011-10-06; 6(10): e25714
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1. PLoS One. 2011;6(10):e25714. doi: 10.1371/journal.pone.0025714. Epub 2011 Oct 6.
Developmental acquisition of a rapid calcium-regulated vesicle supply allows
sustained high rates of exocytosis in auditory hair cells.
Levic S(1), Bouleau Y, Dulon D.
(1)Equipe Neurophysiologie de la Synapse Auditive, Unité Mixte de Recherche,
Inserm U587 et Université Victor Segalen, Institut des Neurosciences de Bordeaux,
Centre Hospitalier Universitaire Pellegrin, Bordeaux, France.
Auditory hair cells (HCs) have the remarkable property to indefinitely sustain
high rates of synaptic vesicle release during ongoing sound stimulation. The
mechanisms of vesicle supply that allow such indefatigable exocytosis at the
ribbon active zone remain largely unknown. To address this issue, we
characterized the kinetics of vesicle recruitment and release in developing chick
auditory HCs. Experiments were done using the intact chick basilar papilla from
E10 (embryonic day 10) to P2 (two days post-hatch) by monitoring changes in
membrane capacitance and Ca(2+) currents during various voltage stimulations.
Compared to immature pre-hearing HCs (E10-E12), mature post-hearing HCs (E18-P2)
can steadily mobilize a larger readily releasable pool (RRP) of vesicles with
faster kinetics and higher Ca(2+) efficiency. As assessed by varying the
inter-pulse interval of a 100 ms paired-pulse depolarization protocol, the
kinetics of RRP replenishment were found much faster in mature HCs. Unlike mature
HCs, exocytosis in immature HCs showed large depression during repetitive
stimulations. Remarkably, when the intracellular concentration of EGTA was raised
from 0.5 to 2 mM, the paired-pulse depression level remained unchanged in
immature HCs but was drastically increased in mature HCs, indicating that the
Ca(2+) sensitivity of the vesicle replenishment process increases during
maturation. Concomitantly, the immunoreactivity of the calcium sensor otoferlin
and the number of ribbons at the HC plasma membrane largely increased, reaching a
maximum level at E18-P2. Our results suggest that the efficient Ca(2+)-dependent
vesicle release and supply in mature HCs essentially rely on the concomitant
engagement of synaptic ribbons and otoferlin at the plasma membrane.
PMID: 21998683 [Indexed for MEDLINE]