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