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Proc Natl Acad Sci U S A. 2015 Mar 3;112(9):E1028-37. doi: 10.1073/pnas.1416424112. Epub 2015 Feb 17.

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

Author information

1
Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, 37099 Göttingen, Germany; Collaborative Research Center 889, University of Göttingen, 37099 Göttingen, Germany; tpangrs@gwdg.de nstrenzke@med.uni-goettingen.de tmoser@gwdg.de.
2
Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, 37099 Göttingen, Germany; Theoretical Neurophysics Group, Max Planck Institute for Dynamics and Self-Organization, 37077 Göttingen, Germany; Bernstein Center for Computational Neuroscience, Göttingen University, 37077 Göttingen, Germany;
3
Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, 37099 Göttingen, Germany; Collaborative Research Center 889, University of Göttingen, 37099 Göttingen, Germany;
4
Unit of Anatomy, Department of Medicine, University of Fribourg, 1700 Fribourg, Switzerland;
5
Collaborative Research Center 889, University of Göttingen, 37099 Göttingen, Germany; Theoretical Neurophysics Group, Max Planck Institute for Dynamics and Self-Organization, 37077 Göttingen, Germany; Bernstein Center for Computational Neuroscience, Göttingen University, 37077 Göttingen, Germany;
6
Collaborative Research Center 889, University of Göttingen, 37099 Göttingen, Germany; Auditory Systems Physiology Group, InnerEarLab, Department of Otolaryngology, University Medical Center Göttingen, 37099 Göttingen, Germany; and Eaton Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Harvard University, Boston, MA 02114 tpangrs@gwdg.de nstrenzke@med.uni-goettingen.de tmoser@gwdg.de.
7
Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, 37099 Göttingen, Germany; Collaborative Research Center 889, University of Göttingen, 37099 Göttingen, Germany; Bernstein Center for Computational Neuroscience, Göttingen University, 37077 Göttingen, Germany; tpangrs@gwdg.de nstrenzke@med.uni-goettingen.de tmoser@gwdg.de.

Abstract

EF-hand Ca(2+)-binding proteins are thought to shape the spatiotemporal properties of cellular Ca(2+) 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 Ca(2+) 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 Ca(2+)-dependent inactivation of their Ca(2+) current. Exocytosis of readily releasable vesicles remained unchanged, in accordance with the estimated tight spatial coupling of Ca(2+) channels and release sites (effective "coupling distance" of 17 nm). Substitution experiments with synthetic Ca(2+) chelators indicated the presence of endogenous Ca(2+) buffers equivalent to 1 mM synthetic Ca(2+)-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 Ca(2+) buffers regulate presynaptic IHC function for metabolically efficient sound coding.

KEYWORDS:

calcium buffers; calcium current; exocytosis; hair cell; synapse

PMID:
25691754
PMCID:
PMC4352837
DOI:
10.1073/pnas.1416424112
[Indexed for MEDLINE]
Free PMC Article

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