EF-hand protein Ca super( 2+) buffers regulate Ca super( 2+) influx and exocytosis in sensory hair cells

EF-hand ...-binding proteins are thought to shape the spatiotemporal properties of cellular ... signaling and are prominently expressed in sensory hair cells in the ear. Here, we combined genetic disruption of parvalbumin- alpha , calbindin-D28k, and calretinin in mice with patch-clamp recording, in...

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Published in:Proceedings of the National Academy of Sciences - PNAS 2015-03, Vol.112 (9), p.E1028-E1028
Main Authors: Pangrsic, Tina, Gabrielaitis, Mantas, Michanski, Susann, Schwaller, Beat, Wolf, Fred, Strenzke, Nicola, Moser, Tobias
Format: Article
Language:English
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Summary:EF-hand ...-binding proteins are thought to shape the spatiotemporal properties of cellular ... signaling and are prominently expressed in sensory hair cells in the ear. Here, we combined genetic disruption of parvalbumin- alpha , calbindin-D28k, and calretinin in mice with patch-clamp recording, in vivo physiology, and mathematical modeling to study their role in ... 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 ...-dependent inactivation of their ... current. Exocytosis of readily releasable vesicles remained unchanged, in accordance with the estimated tight spatial coupling of ... channels and release sites (effective "coupling distance" of 17 nm). Substitution experiments with synthetic ... chelators indicated the presence of endogenous ... buffers equivalent to 1 mM synthetic ...-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 ... buffers regulate presynaptic IHC function for metabolically efficient sound coding. (ProQuest: ... denotes formulae/symbols omitted.)
ISSN:0027-8424