Lajdová I, Okša A, Spustová A, Dzúrik R
Ustav farmakologie, klinickej a experimentalnej farmakologie Lekarskej, Bratislava, Slovenska Republika.
Vnitr Lek. 2012 Jul-Aug;58(7-8):525-30.
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.
游离细胞内钙是许多生物系统中的关键信号介质。钙阳离子（Ca2+）是一种重要的普遍存在的信使，控制着广泛的细胞过程。游离胞质钙浓度（[Ca2+]i）受调节细胞外空间Ca2+内流和细胞内钙库Ca2+释放的机制控制，也受ATP依赖性Ca2+泵和反向转运体活性的控制，这些泵和转运体将Ca2+转运回钙库或排出细胞。慢性肾脏病与[Ca2+]i显著升高有关，这对细胞有毒性，可能导致多器官功能障碍。慢性肾脏病患者细胞钙稳态的紊乱是一个复杂的过程。我们的研究阐明了慢性肾脏病患者外周血单核细胞中细胞钙稳态改变的病理生理机制，外周血单核细胞代表了非兴奋性细胞模型。结果表明，在慢性肾脏病早期，外周血单核细胞中的[Ca2+]i就显著升高。与健康志愿者相比，这些患者细胞内钙库的钙浓度和通过容量性钙内流进入细胞的钙浓度显著更高。此外，形成孔道的P2X7受体也参与了慢性肾脏病患者外周血单核细胞中[Ca2+]i的升高。P2X7受体功能改变和表达增加可能导致慢性肾脏病细胞内钙稳态的复杂紊乱。另一方面，与健康受试者相比，负责将过量钙排出细胞的质膜Ca2+-ATP酶活性降低了25%。这意味着该疾病不仅损害了钙进入细胞的机制，也损害了钙排出细胞的机制。钙信号的所有这些改变很可能导致慢性肾脏病早期[Ca2+]i升高。
