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Inhibition of P2X7 receptors by divalent cations: old action and new insight

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Abstract

P2X family receptors form ATP-gated ion channels by assembling homo/hetero-trimers from seven receptor subunits. The homomeric P2X7 receptor is extraordinary in that in addition to distinctive localization and biological functions it exhibits several hallmark properties, for example, the receptor is potently inhibited by divalent cations such as calcium, magnesium, zinc and copper. Despite the fact that this distinct feature was first described almost three decades ago, our understanding is still contentious. Recent site-directed mutagenesis studies have provided direct evidence showing that functional inhibition by zinc and copper primarily results from direct interaction with the receptor. In this short review, I will give a concise description of the major localization, biological functions, and unique properties of the P2X7 receptor, and particularly discuss the evolving understanding of how divalent cations inhibit the P2X7 receptor and the potential implication of such inhibition to the physiological and pathophysiological role of the P2X7 receptor.

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Acknowledgments

I am grateful to members of the laboratory (X. Liu, H. J. Mao, R. Xia and H. Bradley) and collaborators (A. Surprenant and S. Roger) for their contribution to the work described here, and the BBSRC for support.

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  1. Institute of Membrane and Systems Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK

    Lin-Hua Jiang

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EBSA Satellite meeting: Ion channels, Leeds, July 2007.

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Jiang, LH. Inhibition of P2X7 receptors by divalent cations: old action and new insight. Eur Biophys J 38, 339–346 (2009). https://doi.org/10.1007/s00249-008-0315-y

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