Oncomodulin (OCM) uniquely regulates calcium signaling in neonatal cochlear outer hair cells.

Autor: Murtha KE; Department of Biology, Baylor University, 101 Bagby Ave, Waco, TX, US., Yang Y; Department of Biology, Baylor University, 101 Bagby Ave, Waco, TX, US., Ceriani F; School of Biosciences, University of Sheffield, S10 2TN Sheffield, United Kingdom., Jeng JY; School of Biosciences, University of Sheffield, S10 2TN Sheffield, United Kingdom., Climer LK; Department of Biology, Baylor University, 101 Bagby Ave, Waco, TX, US., Jones F; Department of Biology, Baylor University, 101 Bagby Ave, Waco, TX, US., Charles J; Department of Biology, Baylor University, 101 Bagby Ave, Waco, TX, US., Devana SK; Department of Integrative Biology and Physiology, University of California, Los Angeles, CA, US., Hornak AJ; Department of Biology, Baylor University, 101 Bagby Ave, Waco, TX, US., Marcotti W; School of Biosciences, University of Sheffield, S10 2TN Sheffield, United Kingdom; Sheffield Neuroscience Institute, University of Sheffield, Sheffield, S10 2TN, UK., Simmons DD; Department of Biology, Baylor University, 101 Bagby Ave, Waco, TX, US; School of Biosciences, University of Sheffield, S10 2TN Sheffield, United Kingdom; Department of Integrative Biology and Physiology, University of California, Los Angeles, CA, US; Department of Psychology and Neuroscience, Baylor University, Waco, TX, US. Electronic address: dwayne_simmons@baylor.edu.
Jazyk: angličtina
Zdroj: Cell calcium [Cell Calcium] 2022 Jul; Vol. 105, pp. 102613. Date of Electronic Publication: 2022 Jun 24.
DOI: 10.1016/j.ceca.2022.102613
Abstrakt: In cochlear outer hair cells (OHCs), a network of Ca 2+ channels, pumps and Ca 2+ -binding proteins (CaBPs) regulates the localization, spread, and magnitude of free Ca 2+ ions. During early postnatal development, OHCs express three prominent mobile EF-hand CaBPs: oncomodulin (OCM), α-parvalbumin (APV) and sorcin. We have previously shown that deletion of Ocm (Ocm -/- ) gives rise to progressive cochlear dysfunction in young adult mice. Here, we show that changes in Ca 2+ signaling begin early in postnatal development of Ocm -/- mice. While mutant OHCs exhibit normal electrophysiological profiles compared to controls, their intracellular Ca 2+ signaling is altered. The onset of OCM expression at postnatal day 3 (P3) causes a developmental change in KCl-induced Ca 2+ transients in OHCs and leads to slower KCl-induced Ca 2+ transients than those elicited in cells from Ocm -/- littermates. We compared OCM buffering kinetics with other CaBPs in animal models and cultured cells. In a double knockout of Ocm and Apv (Ocm -/- ;Apv -/- ), mutant OHCs show even faster Ca 2+ kinetics, suggesting that APV may also contribute to early postnatal Ca 2+ signaling. In transfected HEK293T cells, OCM slows Ca 2+ kinetics more so than either APV or sorcin. We conclude that OCM controls the intracellular Ca 2+ environment by lowering the amount of freely available [Ca 2+ ] i in OHCs and transfected HEK293T cells. We propose that OCM plays an important role in shaping the development of early OHC Ca 2+ signals through its inimitable Ca 2+ buffering capacity.
(Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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