ATP-dependent intercellular Ca2+ signaling in the developing cochlea: Facts, fantasies and perspectives

Hearing relies on a sensitive mechanoelectrical transduction process in the cochlea of the inner ear. The cochlea contains sensory, secretory, neural, supporting and epithelial cells which are all essential to the sound transduction process. It is well known that a complex extracellular purinergic signaling system contributes to cochlear homeostasis, altering cochlear sensitivity and neural output via ATP-gated ion channels (P2X receptors) and G protein-coupled P2Y receptors. This review focuses on the emerging roles of ATP that are currently under investigation in the developing sensory epithelium, with particular emphasis on the link between ATP release, Ca2+ signaling, the expression and function of gap junction proteins connexin26 and connexin30, and the acquisition of hearing.

► In the adult cochlea, ATP-dependent mechanisms provide a limited safeguard against noxius effects of sound overstimulation.
► Extracellular ATP is emerging as a key player also in the developmental processes that guide the acquisition of hearing.
► ATP release and IP3-mediated Ca2+ signaling are bidirectionally linked to cochlear connexin expression.
► The proposal that ATP triggers the firing activity of immature inner hair cells is questioned in recent publications.