Calcium- and Otoferlin-Dependent Exocytosis by Immature Outer Hair Cells
Open Access
- 20 February 2008
- journal article
- research article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 28 (8), 1798-1803
- https://doi.org/10.1523/jneurosci.4653-07.2008
Abstract
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; τ = 79 ms) and a slowly releasable pool (τ = 870 ms). The RRP size and maximal release rate were estimated at ∼1200 vesicles and ∼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 exocytosisin vivo. Finally, the evoked membrane capacitance increases were abolished in P2–P3 OHCs from mutantOtof−/−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.Keywords
This publication has 33 references indexed in Scilit:
- Time course and calcium dependence of transmitter release at a single ribbon synapseProceedings of the National Academy of Sciences, 2007
- Spontaneous Discharge Patterns in Cochlear Spiral Ganglion Cells Before the Onset of Hearing in CatsJournal of Neurophysiology, 2007
- Differential expression of otoferlin in brain, vestibular system, immature and mature cochlea of the ratEuropean Journal of Neuroscience, 2006
- Prestin and the cochlear amplifierThe Journal of Physiology, 2006
- Auditory Hair Cell-Afferent Fiber Synapses Are Specialized to Operate at Their Best FrequenciesNeuron, 2005
- Cav1.3 (α1D) Ca2+ Currents in Neonatal Outer Hair Cells of MiceThe Journal of Physiology, 2003
- Synaptic Assembly of the Brain in the Absence of Neurotransmitter SecretionScience, 2000
- Transient expression of NMDA receptors during rearrangement of AMPA-receptor-expressing fibers in the developing inner earCell and tissue research, 1996
- Spontaneous Impulse Activity of Rat Retinal Ganglion Cells in Prenatal LifeScience, 1988
- Morphology, Synaptology and Electrophysiology of the Developing CochleaActa Oto-Laryngologica, 1985