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
-
- Adenosine Triphosphate/physiology*
- Animals
- Calcium Channels/metabolism*
- Cells, Cultured
- Humans
- Macrophages, Peritoneal/cytology
- Macrophages, Peritoneal/metabolism
- Mice
- Permeability
- Receptors, Purinergic P2X7/physiology*
- PubMed
- 25645917 Full text @ J. Biol. Chem.
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.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping