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

Oncomodulin Regulates Spontaneous Calcium Signaling and Maturation of Afferent Innervation in Cochlear Outer Hair Cells

“…GCaMP6s Ocm -/- OHCs exhibited higher baseline fluorescence intensity compared to GCaMP6s Ocm +/+ OHCs (F 0 , Figure 2 ), indicating a possible higher basal level of intracellular Ca 2+ due to the lack of OCM. A similar result has been reported using the ratiometric dye Fura 2 (Murtha et al, 2022). OCM can be detected in P2 GCaMP6s Ocm +/+ OHCs ( Figure 2 ).…”

“…Moreover, we found a gradient expression of OCM along the tonotopic axis of the cochlea of P2 GCaMP6s mice, with a higher OCM level in high-frequency OHC (base, Figure 2 ). These results confirm that OCM protein can be detected as early as P2 in OHCs, similar to other mouse strains (Climer et al, 2019; Murtha et al, 2022).…”

“…In previous studies, we showed that OCM expression in OHCs influences intracellular Ca 2+ signaling during postnatal development. By loading dissected cochlear preparations with the Ca 2+ indicator Fluo-4, we demonstrated that the onset of OCM expression leads to slower KCl-induced Ca 2+ transients than those elicited in OHCs from Ocm -/- littermates (Murtha et al, 2022). Changes in intracellular Ca 2+ induced by extracellular KCl caused increases in GCaMP6s fluorescence in OHCs ( Figure 3A, Movie 1 ).…”

“…To investigate how OCM regulates spontaneous Ca 2+ activity in developing OHCs, we expressed a genetically encoded, tissue-specific Ca 2+ sensor ( Atoh1 -GCaMP6s) in Ocm wild-type ( Ocm +/+ ) and Ocm knockout ( Ocm -/- ) mice. GCaMP6s Ocm -/- mice exhibited early onset hearing loss, and their OHCs showed faster KCl-induced Ca 2+ transients than those recorded from GCaMP6s Ocm +/+ mice and other mouse strains (Climer et al, 2021; Murtha et al, 2022; Tong et al, 2016). In neonatal mice (P2), we observed spontaneous Ca 2+ activity in OHCs that was synchronized by Ca 2+ waves elicited in the greater epithelial ridge (GER).…”

“…OCM is an important CaBP for which targeted deletion causes hearing loss (Pangrsic et al, 2015; Tong et al, 2016). The absence of OCM uniquely alters Ca 2+ signaling in OHCs before the onset of hearing (Murtha et al, 2022). Given that spontaneous Ca 2+ activity plays a major role in OHC development, we hypothesized that OCM modulates spontaneous Ca 2+ activity during development.…”