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bioRxiv · 10.1101/2022.03.03.482327

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

Murtha, K. E.·Yang, Y.·Ceriani, F.·Jeng, J.-Y.·Climer, L.·Jones, F.·Charles, J.·Devana, S.·Hornak, A.·Marcotti, W.·Simmons, D. D.
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Abstract

In cochlear outer hair cells (OHCs), a network of Ca2+ channels, pumps and Ca2+-binding proteins (CaBPs) regulates the localization, spread, and magnitude of free Ca2+ ions. During early postnatal development, OHCs express three prominent mobile EF-hand CaBPs: oncomodulin (OCM), -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 Ca2+ signaling begin early in postnatal development of Ocm-/- mice. While mutant OHCs exhibit normal electrophysiological profiles compared to controls, their intracellular Ca2+ signaling is altered. The onset of OCM expression at postnatal day 3 (P3) causes a developmental change in KCl-induced Ca2+ transients in OHCs and leads to slower KCl-induced Ca2+ 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 Ca2+ kinetics, suggesting that APV may also contribute to early postnatal Ca2+ signaling. In transfected HEK293T cells, OCM slows Ca2+ kinetics more so than either APV or sorcin. We conclude that OCM controls the intracellular Ca2+ environment by lowering the amount of freely available [Ca2+]i in OHCs and in transfected HEK293T cells. We propose that OCM plays an important role in shaping the development of early OHC Ca2+ signals through its inimitable Ca2+ buffering capacity.

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Murtha, K. E., Yang, Y., Ceriani, F., Jeng, J.-Y., Climer, L., Jones, F., Charles, J., Devana, S., Hornak, A., Marcotti, W., Simmons, D. D.. 2022-03-04. Oncomodulin (OCM) uniquely regulates calcium signaling in neonatal cochlear outer hair cells.. https://doi.org/10.1101/2022.03.03.482327

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