PUBLICATION

Quantifying Ca2+ Current and Permeability in ATP-gated P2X7 Receptors

Authors
Liang, X., Samways, D.S., Wolf, K., Bowles, E.A., Richards, J.P., Bruno, J., Dutertre, S., DiPaolo, R.J., Egan, T.M.
ID
ZDB-PUB-150204-6
Date
2015
Source
The Journal of biological chemistry   290(12): 7930-42 (Journal)
Registered Authors
Keywords
calcium transport, fractional calcium current, ion channel, ligand-gated ion channel, lymphocyte, macrophage, pore dilation, purinergic receptor, relative calcium permeability
MeSH Terms
  • Calcium Channels/metabolism*
  • Receptors, Purinergic P2X7/physiology*
  • Animals
  • Cells, Cultured
  • Adenosine Triphosphate/physiology*
  • Permeability
  • Mice
  • Humans
  • Macrophages, Peritoneal/cytology
  • Macrophages, Peritoneal/metabolism
(all 10)
PubMed
25645917 Full text @ J. Biol. Chem.
Abstract
ATP-gated P2X7 receptors are prominently expressed in inflammatory cells and play a key role in the immune response. A major consequence of receptor activation is the regulated influx of Ca2+. Although the physiological importance of the resulting rise in intracellular Ca2+ is universally acknowledged, the biophysics of the Ca2+ current responsible for the effects are poorly understood, largely because traditional methods of measuring Ca2+ permeability are difficult to apply to P2X7 receptors. Here we use an alternative approach, called dye-overload patch-clamp photometry, to quantify the agonist-gated Ca2+ current of recombinant P2X7 receptors of dog, guinea-pig, human, monkey, mouse, rat, and zebrafish. We find that the magnitude of the current depends on the species of origin, the splice variant, and the concentration of the purinergic agonist. We also measured a significant contribution of Ca2+ to the agonist-gated current of the native P2X7Rs of mouse and human macrophages. Our results provide cross-species quantitative measures of the Ca2+ currents of P2X7 receptors for the first time, and suggest that the cytoplasmic N-terminus play a meaningful role in regulating the flow of Ca2+ through the channel.
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Citation
Liang, X., Samways, D.S., Wolf, K., Bowles, E.A., Richards, J.P., Bruno, J., Dutertre, S., DiPaolo, R.J., Egan, T.M. (2015) Quantifying Ca2+ Current and Permeability in ATP-gated P2X7 Receptors. The Journal of biological chemistry. 290(12):7930-42.