title: Quantifying Ca2+ current and permeability in ATP-gated P2X7 receptors.
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 Ca(2+) through the self-contained cation non-selective channel. Although the physiological importance of the resulting rise in intracellular Ca(2+) is universally acknowledged, the biophysics of the Ca(2+) flux responsible for the effects are poorly understood, largely because traditional methods of measuring Ca(2+) 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 Ca(2+) flux of recombinant P2X7 receptors of dog, guinea pig, human, monkey, mouse, rat, and zebrafish. We find that the magnitude of the Ca(2+) component of the ATP-gated current depends on the species of origin, the splice variant, and the concentration of the purinergic agonist. We also measured a significant contribution of Ca(2+) to the agonist-gated current of the native P2X7Rs of mouse and human immune cells. Our results provide cross-species quantitative measures of the Ca(2+) current of the P2X7 receptor for the first time, and suggest that the cytoplasmic N terminus plays a meaningful role in regulating the flow of Ca(2+) through the channel.
authors: From the Department of Pharmacological and Physiological Science and Center for Neuroscience, and.
authors: Xin
authors: X
authors: Liang
authors: the Department of Biology, Clarkson University, Potsdam, New York 13699, and.
authors: Damien S K
authors: DS
authors: Samways
authors: the Departments of Molecular Microbiology and Immunology and.
authors: Kyle
authors: K
authors: Wolf
authors: From the Department of Pharmacological and Physiological Science and Center for Neuroscience, and.
authors: Elizabeth A
authors: EA
authors: Bowles
authors: From the Department of Pharmacological and Physiological Science and Center for Neuroscience, and.
authors: Jennifer P
authors: JP
authors: Richards
authors: Internal Medicine, Saint Louis University School of Medicine, St. Louis, Missouri 63104.
authors: Jonathan
authors: J
authors: Bruno
authors: the Institut des Biomolécules Max Mousseron, UMR 5247, Université Montpellier 2, CNRS, Montpellier, France.
authors: Sébastien
authors: S
authors: Dutertre
authors: the Departments of Molecular Microbiology and Immunology and.
authors: Richard J
authors: RJ
authors: DiPaolo
authors: From the Department of Pharmacological and Physiological Science and Center for Neuroscience, and egantm@slu.edu.
authors: Terrance M
authors: TM
authors: Egan
mesh_terms: D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000378:metabolism; D051379:Mice; D010539:Permeability; D058486:Receptors, Purinergic P2X7 / Q000502:physiology*
chemical_list: D015220:Calcium Channels; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate
keywords: Calcium Transport; Fractional Calcium Current; Ion Channel; Ligand-gated Ion Channel; Lymphocyte; Macrophage; Pore Dilation; Purinergic Receptor; Relative Calcium Permeability
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