P2X7 receptor-mediated calcium dynamics in HEK293 cells: experimental characterization and modelling approach

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.