Vnitr Lek 2012, 58(7-8):48-53

Chronic kidney disease and cellular calcium homeostasis

I. Lajdová*, A. Okša, A. Spustová, R. Dzúrik
Ústav farmakológie, klinickej a experimentálnej farmakológie Lekárskej fakulty SZU Bratislava, Slovenská republika, prednosta prof. MUDr. Jozef Holomáň, CSc.

Free intracellular calcium represents a critical signaling mediator in a number of biological systems. Calcium cations (Ca2+) are an important ubiquitous messenger, controlling a broad range of cellular processes. Free cytosolic calcium concentration ([Ca2+]i) is controlled by mechanisms that regulate Ca2+ entry from the extracellular space and Ca2+ release from intracellular stores, and by the activity of ATP-dependent Ca2+ pumps and antiporters that move Ca2+ back into stores or out of cells. Chronic kidney disease is associated with a significant elevation in [Ca2+]i which is toxic to the cells and may be responsible for a multiple organ dysfunction. Disturbances in cellular calcium homeostasis in patients with chronic kidney disease represent a complex process. Our studies elucidate pathophysiological mechanisms of altered cellular calcium homeostasis in the peripheral blood mononuclear cells which represent the model of nonexcitable cells in patients with chronic kidney disease. The results demonstrate that [Ca2+]i is significantly increased in peripheral blood mononuclear cells already in early stages of chronic kidney disease. The calcium concentration of intracellular stores and the capacitative calcium entry into the cells of these patients are significantly higher in comparison with healthy volunteers. Also the pore-forming P2X7 receptors participate in increased [Ca2+]i in peripheral blood mononuclear cells of patients with chronic kidney disease. An altered P2X7 receptor function and increased P2X7 receptor expression may contribute to the complex disturbances in intracellular calcium homeostasis in chronic kidney disease. On the other hand, the activity of plasmatic membrane Ca2+-ATPases which is responsible for removing excessive calcium out of the cell, was found to be decreased by 25 % when compared to healthy subjects. It means that not only the mechanisms of entry, but also of the removal are impaired by the disease. All these alterations in calcium signaling are contributing very likely to the elevated [Ca2+]i from early stages of chronic kidney disease.

Keywords: intracelullar calcium; chronic kidney disease; calcium signaling and regulation

Received: May 18, 2012; Published: July 1, 2012  Show citation

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Lajdová I, Okša A, Spustová A, Dzúrik R. Chronic kidney disease and cellular calcium homeostasis. Vnitr Lek. 2012;58(7-8):48-53.
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