Inhibition of P2X(7) receptors by divalent cations: old action and new insight.
P2X family receptors form ATP-gated ion channels by assembling homo/hetero-trimers from seven receptor subunits. The homomeric P2X(7) 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 P2X(7) receptor, and particularly discuss the evolving understanding of how divalent cations inhibit the P2X(7) receptor and the potential implication of such inhibition to the physiological and pathophysiological role of the P2X(7) receptor.
Jiang
Lin-Hua
LH
Institute of Membrane and Systems Biology, Faculty of Biological Sciences, University of Leeds, Leed LS29JT, UK. l.h.jiang@leeds.ac.uk
D000818:Animals; D002413:Cations, Divalent / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D058486:Receptors, Purinergic P2X7
D002413:Cations, Divalent; C546468:P2RX7 protein, human; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7