Purinergic P2X7 receptors participate in disturbed intracellular calcium homeostasis in peripheral blood mononuclear cells of patients with chronic kidney disease

Kidney Blood Press Res. 2012;35(1):48-57. doi: 10.1159/000330349. Epub 2011 Aug 19.


Background: P2X(7) receptors intervene with lymphocyte activation and are responsible for multiple processes, including calcium influx. Here, we studied the participation of P2X(7) 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(2+)](i)) was measured using fluorimetry. The P2X(7) pore function was evaluated by the fluorescent dye ethidium bromide.

Results: In peripheral blood mononuclear cells (PBMCs) of patients, [Ca(2+)](i), intracellular calcium stores and the capacitative calcium entry were increased when compared with healthy subjects. The agonist of P2X(7) receptor BzATP caused a sustained increase in [Ca(2+)](i) in both groups, but the effect was smaller in patients. The antagonist at the P2X(7) receptor KN-62 reduced [Ca(2+)](i) in patients, but had no effect in healthy subjects. In patients, the permeability of ethidium bromide through P2X(7) 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(7) receptors are involved in these pathophysiological processes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
  • Adenosine Triphosphate / analogs & derivatives
  • Adenosine Triphosphate / pharmacology
  • Adult
  • Calcium Signaling / drug effects*
  • Calcium Signaling / physiology
  • Female
  • Homeostasis / drug effects*
  • Homeostasis / physiology
  • Humans
  • Intracellular Fluid / metabolism*
  • Leukocytes, Mononuclear / metabolism*
  • Leukocytes, Mononuclear / pathology
  • Male
  • Middle Aged
  • Receptors, Purinergic P2X7 / physiology*
  • Renal Insufficiency, Chronic / metabolism*
  • Renal Insufficiency, Chronic / pathology
  • Renal Insufficiency, Chronic / therapy*


  • Receptors, Purinergic P2X7
  • 3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate
  • KN 62
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Adenosine Triphosphate