Extracellular ATP elevates cytosolic Ca2+ in cochlear inner hair cells

The local extracellular application of ATP to isolated sensory inner hair cells (IHC) generated a rapid and transient increase in the concentration of cytosolic free Ca2+, peaking within 1 to 5 s. The dose-response curve indicated a half-max stimulation to be 5 microM ATP. The application of the structural derivatives ADP and alpha-beta-methyleneATP did not generate significant Ca2+ response. By contrast, ATP-alpha-S, an agonist for P2z receptor, was fully active in generating Ca2+ responses. In the absence of extracellular free calcium, the ATP-induced Ca2+ increase was still observed, indicating that ATP generated the liberation of Ca2+ from internal stores. These results suggest that extracellular ATP, through an activation of P2-purinergic receptors, may have a neuromodulatory role in the cochlear physiology at the level of the IHC.