Journal article

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

  • Pangršič, Tina Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Germany
  • Gabrielaitis, Mantas Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Germany
  • Michanski, Susann Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Germany
  • Schwaller, Beat Unit of Anatomy, Department of Medicine, University of Fribourg, Switzerland
  • Wolf, Fred Collaborative Research Center 889, University of Göttingen, Germany
  • Strenzke, Nicola Collaborative Research Center 889, University of Göttingen, Germany
  • Moser, Tobias Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Germany
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    03.03.2015
Published in:
  • Proceedings of the National Academy of Sciences. - 2015, vol. 112, no. 9, p. E1028–E1037
English 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.
Faculty
Faculté des sciences et de médecine
Department
Département de Médecine
Language
  • English
Classification
Biological sciences
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/304218
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