Purinergic P2X7 receptors participate in disturbed intracellular calcium homeostasis in peripheral blood mononuclear cells of patients with chronic kidney disease.
2012
Background: P2X7 receptors intervene with lymphocyte activation and are responsible for multiple processes, including calcium influx. Here, we studied the participation of P2X7 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 ([Ca2+]i) was measured using fluorimetry. The P2X7 pore function was evaluated by the fluorescent dye ethidium bromide. Results: In peripheral blood mononuclear cells (PBMCs) of patients, [Ca2+]i, intracellular calcium stores and the capacitative calcium entry were increased when compared with healthy subjects. The agonist of P2X7 receptor BzATP caused a sustained increase in [Ca2+]i in both groups, but the effect was smaller in patients. The antagonist at the P2X7 receptor KN-62 reduced [Ca2+]i in patients, but had no effect in healthy subjects. In patients, the permeability of ethidium bromide through P2X7 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 P2X7 receptors are involved in these pathophysiological processes.
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