Abstract
Background: P2X<sub>7</sub> receptors intervene with lymphocyte activation and are responsible for multiple processes, including calcium influx. Here, we studied the participation of P2X<sub>7</sub> receptors in disturbed intracellular calcium homeostasis regulation in early-stage chronic kidney disease (CKD). Methods: The study involved 20 healthy volunteers and 20 CKD stage 2–3 patients. The free cytosolic calcium concentration ([Ca<sup>2+</sup>]<sub>i</sub>) was measured using fluorimetry. The P2X<sub>7</sub> pore function was evaluated by the fluorescent dye ethidium bromide. Results: In peripheral blood mononuclear cells (PBMCs) of patients, [Ca<sup>2+</sup>]<sub>i</sub>, intracellular calcium stores and the capacitative calcium entry were increased when compared with healthy subjects. The agonist of P2X<sub>7</sub> receptor BzATP caused a sustained increase in [Ca<sup>2+</sup>]<sub>i</sub> in both groups, but the effect was smaller in patients. The antagonist at the P2X<sub>7</sub> receptor KN-62 reduced [Ca<sup>2+</sup>]<sub>i</sub> in patients, but had no effect in healthy subjects. In patients, the permeability of ethidium bromide through P2X<sub>7</sub> pores, as well as through BzATP-activated and KN-62-inhibited pores, was distinct from permeability in healthy volunteers. Conclusions: These results demonstrate that the calcium signaling pathway in PBMCs of CKD patients is defective already in CKD stage 2–3, and the pore-forming P2X<sub>7</sub> receptors are involved in these pathophysiological processes.
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