期刊
NATURE NEUROSCIENCE
卷 13, 期 1, 页码 45-U201出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nn.2456
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资金
- Wellcome Trust
- Deafness Research UK
- University of Sheffield Devolved Funds
- Royal Society
- Deutsche Forschungsgameinschft [316-4-1]
- Baden-Wurttemberg Graduate Programme of the University of Tubingen
Mammalian cochlear inner hair cells (IHCs) are specialized for the dynamic coding of continuous and finely graded sound signals. This ability is largely conferred by the linear Ca2+ dependence of neurotransmitter release at their synapses, which is also a feature of visual and olfactory systems. The prevailing hypothesis is that linearity in IHCs occurs through a developmental change in the Ca2+ sensitivity of synaptic vesicle fusion from the nonlinear (high order) Ca2+ dependence of immature spiking cells. However, the nature of the Ca2+ sensor(s) of vesicle fusion at hair cell synapses is unknown. We found that synaptotagmin IV was essential for establishing the linear exocytotic Ca2+ dependence in adult rodent IHCs and immature outer hair cells. Moreover, the expression of the hitherto undetected synaptotagmins I and II correlated with a high-order Ca2+ dependence in IHCs. We propose that the differential expression of synaptotagmins determines the characteristic Ca2+ sensitivity of vesicle fusion at hair cell synapses.
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