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

• Published in: Cell calcium (Edinburgh) 2022-07, Vol.105, p.102613-102613, Article 102613
• Main Authors: Murtha, Kaitlin E., Yang, Yang, Ceriani, Federico, Jeng, Jing-Yi, Climer, Leslie K., Jones, Forrest, Charles, Jack, Devana, Sai K., Hornak, Aubrey J., Marcotti, Walter, Simmons, Dwayne D.
• Format: Article
• Language: English
• ISSN: 0143-4160; 1532-1991
• DOI: 10.1016/j.ceca.2022.102613

• Onset of oncomodulin expression occurs at postnatal day 3, which correlates with increased calcium buffering in cochlear outer hair cells • Deletion of oncomodulin alters the expression patterns of α-parvalbumin and sorcin during early development of outer hair cells • Oncomodulin and α-parvalbumin both contribute to OHC calcium homeostasis during early postnatal development • Oncomodulin exhibits faster calcium-buffering compared to either α-parvalbumin or sorcin when transiently expressed in HEK293T cells 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. Image, graphical abstract