title: P2X7 receptor-mediated calcium dynamics in HEK293 cells: experimental characterization and modelling approach.
abstract: The P2X7 receptor (P2X7R) induces ionotropic Ca²⁺ signalling in different cell types. It plays an important role in the immune response and in the nervous system. Here, the mechanisms underlying intracellular Ca²⁺ variations evoked by 3'-O-(4-benzoyl)benzoyl-ATP (BzATP), a potent agonist of the P2X7R, in transfected HEK293 cells, are investigated both experimentally and theoretically. We propose a minimal model of P2X7R that is capable of reproducing, qualitatively and quantitatively, the experimental data. This approach was also adopted for the P2X7R variant, which lacks the entire C-terminus tail (trP2X7R). Then we introduce a biophysical model describing the Ca²⁺ dynamics in HEK293. Our model gives an account of the ionotropic Ca²⁺ influx evoked by BzATP on the basis of the kinetics model of P2X7R. To explain the complex Ca²⁺ responses evoked by BzATP, the model predicted that an impairment in Ca²⁺ extrusion flux through the plasma membrane is a key factor for Ca²⁺ homeostasis in HEK293 cells.
authors.affiliation: CNR-Institute of Biophysics, via G Moruzzi 1, 56124 Pisa, Italy. digarbo@pi.ibf.cnr.it
authors.forename: A
authors.initials: A
authors.lastname: Di Garbo
authors.forename: S
authors.initials: S
authors.lastname: Alloisio
authors.forename: M
authors.initials: M
authors.lastname: Nobile
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D008274:Magnesium / Q000378:metabolism; D008954:Models, Biological; D051381:Rats; D058486:Receptors, Purinergic P2X7 / Q000737:chemistry* / Q000378:metabolism*; D014162:Transfection
chemical_list: C546470:P2rx7 protein, rat; D058486:Receptors, Purinergic P2X7; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; D000255:Adenosine Triphosphate; D008274:Magnesium; D002118:Calcium