CNR-Institute of Biophysics, via G Moruzzi 1, 56124 Pisa, Italy.
Phys Biol. 2012;9(2):026001. doi: 10.1088/1478-3975/9/2/026001. Epub 2012 Apr 3.
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.
P2X7 受体（P2X7R）在不同细胞类型中诱导离子型 Ca²⁺信号。它在免疫反应和神经系统中起着重要作用。在这里，我们通过实验和理论研究了转染的 HEK293 细胞中 3'-O-(4-苯甲酰基)苯甲酰基-ATP（BzATP）引发的细胞内 Ca²⁺变化的机制，BzATP 是 P2X7R 的一种有效激动剂。我们提出了一个能够定性和定量再现实验数据的 P2X7R 最小模型。这种方法也适用于缺乏整个 C 端尾巴的 P2X7R 变体（trP2X7R）。然后，我们引入了一个描述 HEK293 中 Ca²⁺动力学的生物物理模型。我们的模型基于 P2X7R 的动力学模型解释了 BzATP 引发的离子型 Ca²⁺内流。为了解释 BzATP 引发的复杂 Ca²⁺反应，该模型预测，通过质膜的 Ca²⁺外排通量受损是 HEK293 细胞中 Ca²⁺动态平衡的关键因素。
