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Intercellular Ca(2+) waves can coordinate the action of large numbers of cells over significant distances. Recent work in many different systems has indicated that the release of ATP is fundamental for the propagation of most Ca(2+) waves. In the organ of hearing, the cochlea, ATP release is involved in critical signalling events during tissue maturation. ATP-dependent signalling is also implicated in the normal hearing process and in sensing cochlear damage. Here, we show that two distinct Ca(2+) waves are triggered during damage to cochlear explants. Both Ca(2+) waves are elicited by extracellular ATP acting on P2 receptors, but they differ in their source of Ca(2+), their velocity, their extent of spread and the cell type through which they propagate. A slower Ca(2+) wave (14 mum/s) communicates between Deiters' cells and is mediated by P2Y receptors and Ca(2+) release from IP(3)-sensitive stores. In contrast, a faster Ca(2+) wave (41 mum/s) propagates through sensory hair cells and is mediated by Ca(2+) influx from the external environment. Using inhibitors and selective agonists of P2 receptors, we suggest that the faster Ca(2+) wave is mediated by P2X(4) receptors. Thus, in complex tissues, the expression of different receptors determines the propagation of distinct intercellular communication signals.

Damage-induced cell–cell communication in different cochlear cell types via two distinct ATP-dependent Ca2+ waves