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Journal Article

Developmental refinement of hair cell synapses tightens the coupling of Ca2+ influx to exocytosis.

MPS-Authors
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Goettfert,  F.
Department of NanoBiophotonics, MPI for Biophysical Chemistry, Max Planck Society;

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Hell,  S.
Department of NanoBiophotonics, MPI for Biophysical Chemistry, Max Planck Society;

Fulltext (public)

1938067.pdf
(Publisher version), 4MB

Supplementary Material (public)

1938067_Suppl_1.pdf
(Supplementary material), 88KB

1938067_Suppl_2.pdf
(Supplementary material), 173KB

1938067_Suppl_3.pdf
(Supplementary material), 112KB

1938067_Suppl_4.pdf
(Supplementary material), 92KB

1938067-_Suppl_5.pdf
(Supplementary material), 165KB

1938067_Suppl_6.pdf
(Supplementary material), 142KB

1938067_Suppl_7.pdf
(Supplementary material), 138KB

1938067_Suppl_8.pdf
(Supplementary material), 140KB

1938067_Suppl_9.pdf
(Supplementary material), 228KB

1938067_Suppl_10.pdf
(Supplementary material), 44KB

Citation

Wong, A. B., Rutherford, M. A., Gabrielaitis, M., Pangrsic, T., Goettfert, F., Frank, T., et al. (2014). Developmental refinement of hair cell synapses tightens the coupling of Ca2+ influx to exocytosis. EMBO Journal, 33, 247-264. doi:10.1002/embj.201387110.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0015-82B8-A
Abstract
Cochlear inner hair cells (IHCs) develop from pre‐sensory pacemaker to sound transducer. Here, we report that this involves changes in structure and function of the ribbon synapses between IHCs and spiral ganglion neurons (SGNs) around hearing onset in mice. As synapses matured they changed from holding several small presynaptic active zones (AZs) and apposed postsynaptic densities (PSDs) to one large AZ/PSD complex per SGN bouton. After the onset of hearing (i) IHCs had fewer and larger ribbons; (ii) CaV1.3 channels formed stripe‐like clusters rather than the smaller and round clusters at immature AZs; (iii) extrasynaptic CaV1.3‐channels were selectively reduced, (iv) the intrinsic Ca2+ dependence of fast exocytosis probed by Ca2+ uncaging remained unchanged but (v) the apparent Ca2+ dependence of exocytosis linearized, when assessed by progressive dihydropyridine block of Ca2+ influx. Biophysical modeling of exocytosis at mature and immature AZ topographies suggests that Ca2+ influx through an individual channel dominates the [Ca2+] driving exocytosis at each mature release site. We conclude that IHC synapses undergo major developmental refinements, resulting in tighter spatial coupling between Ca2+ influx and exocytosis.