KCNQ4 Deficiency Induces Apoptotic Activation and Innervation Changes in Deiters’ Cells

The organ of Corti is a specialized sensory epithelium where interactions between hair cells (HCs) and supporting cells (SCs) are critical for cochlear function. Although KCNQ4 potassium channel deficiency causes progressive outer hair cell degeneration and hearing loss (HL), the involvement of SCs, particularly Deiters’ cells (DCs), remains poorly understood. We analyzed DC survival, apoptotic activity, and innervation changes in a Kcnq4 knockout (KO) mouse model. DC distribution was quantified at 4 and 10 weeks using cytocochleograms and three-dimensional confocal reconstructions of phalloidin-labeled whole-mount cochleae. Apoptotic signaling was evaluated by immunodetection of cleaved caspase-3 (cCas3), whereas synaptophysin (SYN) labeling was used to assess presynaptic structures. Despite extensive OHC degeneration, DC numbers remained preserved throughout the cochlea at both ages. However, cCas3 immunoreactivity increased in the DC region, particularly in basal segments, and became more pronounced with age. In addition, the DC region showed a higher density of SYN-positive puncta, suggesting changes in local neural inputs. These findings show that OHC loss in Kcnq4 KO mice is accompanied by apoptotic signaling and altered innervation within the DC region. The preservation of DCs despite increased cellular stress suggests that these SCs may engage adaptive responses to disrupted K+ homeostasis, highlighting a potential compensatory role of DCs during KCNQ4-associated.