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

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Abstract

Intercellular Ca2+ 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 Ca2+ 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 Ca2+ waves are triggered during damage to cochlear explants. Both Ca2+ waves are elicited by extracellular ATP acting on P2 receptors, but they differ in their source of Ca2+, their velocity, their extent of spread and the cell type through which they propagate. A slower Ca2+ wave (14 μm/s) communicates between Deiters’ cells and is mediated by P2Y receptors and Ca2+ release from IP3-sensitive stores. In contrast, a faster Ca2+ wave (41 μm/s) propagates through sensory hair cells and is mediated by Ca2+ influx from the external environment. Using inhibitors and selective agonists of P2 receptors, we suggest that the faster Ca2+ wave is mediated by P2X4 receptors. Thus, in complex tissues, the expression of different receptors determines the propagation of distinct intercellular communication signals.

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Authors and Affiliations

  1. UCL Ear Institute, University College London, 332 Gray’s Inn Road, London, WC1X 8EE, UK

    Manuela Lahne & Jonathan E. Gale

  2. Department of Cell and Developmental Biology, University College London, Gower Street, WC1E 6BT, London, UK

    Jonathan E. Gale

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  1. Manuela Lahne
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  2. Jonathan E. Gale
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Correspondence to Jonathan E. Gale.

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Supplementary Fig. 1

Two distinct sources of Ca2+ are required for wave propagation in the HC region. a–f Peak [Ca2+]i changes as a function of distance from the lesion site measured in ROIs placed along the HC region (as shown in Fig. 2a, pre) comparing (a–c) control (black rectangle) against 0 Ca2+ (a, red triangle), U73122 (b, grey rectangle) and U73122 + 0 Ca2+. (c, blue diamond). d, e Comparison of peak [Ca2+]i changes of (d) 0 Ca2+- or (e) U73122-treated explants to those exposed to U73122 + 0 Ca2+. Mean ± SEM, n = 22 (control), n = 6 (0 Ca2+), n = 7 (U73122), n = 7 (U73122 + 0 Ca2+). Analysis of variance and individual Student’s t tests, *p < 0.05 (TIFF 2949 kb) (GIF 106 kb)

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Lahne, M., Gale, J.E. Damage-induced cell–cell communication in different cochlear cell types via two distinct ATP-dependent Ca2+ waves. Purinergic Signalling 6, 189–200 (2010). https://doi.org/10.1007/s11302-010-9193-8

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  • DOI: https://doi.org/10.1007/s11302-010-9193-8

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