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Journal Article

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

MPS-Authors

Gabrielaitis,  Mantas
Research Group Theoretical Neurophysics, Max Planck Institute for Dynamics and Self-Organization, Max Planck Society;

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Wolf,  Fred
Research Group Theoretical Neurophysics, Max Planck Institute for Dynamics and Self-Organization, Max Planck Society;

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Citation

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.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0029-A8BD-2
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.