biostudies-literaturePangrsic TBundesministerium für Bildung und ForschungDeutsche ForschungsgemeinschaftAlexander von Humboldt-StiftungE1028-37https://www.ebi.ac.uk/biostudies/studies/S-EPMC4352837biostudies-literatureUnknown112(9)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 "couplinProceedings of the National Academy of Sciences of the United States of AmericaEF-hand protein Ca2+ buffers regulate Ca2+ influx and exocytosis in sensory hair cells.PMC4352837CRC88901GQ1005Afellowship01GQ0811Gabrielaitis MStrenzke NMichanski SPangrsic TWolf FSchwaller BMoser TfalseEF-hand protein Ca2+ buffers regulate Ca2+ influx and exocytosis in sensory hair cells.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 "couplin2015-01-01T00:00:00Z2015 Mar2025-04-18T15:30:14.286Z2019-03-27T01:47:47ZS-EPMC43528372569175410.1073/pnas.1416424112