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  EF-hand protein Ca2+ buffers regulate Ca2+ influx and exocytosis in sensory hair cells

Pangršič, T., Gabrielaitis, M., Michanski, S., Schwaller, B., Wolf, F., Strenzke, N., et al. (2015). EF-hand protein Ca2+ buffers regulate Ca2+ influx and exocytosis in sensory hair cells. Proceedings of the National Academy of Sciences of the United States of America, 112(9), E1028-E1037. doi:10.1073/pnas.1416424112.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0029-A8BD-2 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002A-C471-6
Genre: Journal Article

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 Creators:
Pangršič, Tina, Author
Gabrielaitis, Mantas1, Author
Michanski, Susann, Author
Schwaller, Beat, Author
Wolf, Fred1, Author              
Strenzke, Nicola, Author
Moser, Tobias, Author
Affiliations:
1Research Group Theoretical Neurophysics, Max Planck Institute for Dynamics and Self-Organization, Max Planck Society, ou_2063289              

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Free keywords: Calcium buffers; Exocytosis; Calcium current; Synapse; Hair cell
 Abstract: EF-hand Ca2+-binding proteins are thought to shape the spatiotemporal properties of cellular Ca2+ signaling and are prominently expressed in sensory hair cells in the ear. Here, we combined genetic disruption of parvalbumin-α, calbindin-D28k, and calretinin in mice with patch-clamp recording, in vivo physiology, and mathematical modeling to study their role in Ca2+ signaling, exocytosis, and sound encoding at the synapses of inner hair cells (IHCs). IHCs lacking all three proteins showed excessive exocytosis during prolonged depolarizations, despite enhanced Ca2+-dependent inactivation of their Ca2+ current. Exocytosis of readily releasable vesicles remained unchanged, in accordance with the estimated tight spatial coupling of Ca2+ channels and release sites (effective “coupling distance” of 17 nm). Substitution experiments with synthetic Ca2+ chelators indicated the presence of endogenous Ca2+ buffers equivalent to 1 mM synthetic Ca2+-binding sites, approximately half of them with kinetics as fast as 1,2-Bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA). Synaptic sound encoding was largely unaltered, suggesting that excess exocytosis occurs extrasynaptically. We conclude that EF-hand Ca2+ buffers regulate presynaptic IHC function for metabolically efficient sound coding.

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Language(s): eng - English
 Dates: 2015-02-172015-03-03
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: BibTex Citekey: PangrsicGabrielaitisMichanskiEtAl2015
DOI: 10.1073/pnas.1416424112
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Title: Proceedings of the National Academy of Sciences of the United States of America
Source Genre: Journal
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Publ. Info: Washington, D.C. : National Academy of Sciences
Pages: - Volume / Issue: 112 (9) Sequence Number: - Start / End Page: E1028 - E1037 Identifier: ISSN: 0027-8424
CoNE: https://pure.mpg.de/cone/journals/resource/954925427230