Inorganic polyphosphate (polyP) is an ancient polymer, which was proven to be a signalling molecule in the mammalian brain, mediating the communication between astrocytes via activation of P2Y₁ purinoreceptors and modulating the activity of neurons. There is very limited information regarding the ability of polyP to transmit the information as an agonist of purinoreceptors in other cells and tissues. Here, we show that application of polyP to the suspension of primary thymocytes increases the concentration of intracellular calcium. PolyP evoked calcium signal was dependent on the presence of P2X inhibitors but not P2Y₁ inhibitor. PolyP dependent increase in intracellular calcium concentration caused mild mitochondrial depolarization, which was dependent on inhibitors of purinoreceptors, extracellular calcium and inhibitor of mitochondrial calcium uniporter but wasn't dependent on cyclosporin A. Application of polyP modulated cell volume regulation machinery of thymocytes in calcium dependent manner. Molecular docking experiments revealed that polyP can potentially bind to several types of P2X receptors with binding energy similar to ATP - natural agonist of P2X purinoreceptors. Further molecular dynamics simulations with P2X₄ showed that binding of one molecule of polyP dramatically increases permeability of this receptor-channel for water molecules. Thus, in this research we for the first time showed that polyP can interact with P2X receptors in thymocytes and modulate physiological processes.

_{无机多磷酸盐 (polyP) 是一种古老的聚合物，已被证明是哺乳动物大脑中的信号分子，通过激活 P2Y 1}嘌呤受体介导星形胶质细胞之间的通讯并调节神经元的活动。关于 PolyP 作为嘌呤受体激动剂在其他细胞和组织中传递信息的能力，信息非常有限。在这里，我们证明将聚磷应用到原代胸腺细胞悬浮液中会增加细胞内钙的浓度。PolyP 诱发的钙信号依赖于 P2X 抑制剂的存在，但不依赖于 P2Y ₁抑制剂的存在。PolyP依赖性细胞内钙浓度增加引起轻度线粒体去极化，该去极化依赖于嘌呤受体抑制剂、细胞外钙和线粒体钙单向转运蛋白抑制剂，但不依赖于环孢菌素A。PolyP调节的胸腺细胞体积调节机制在钙依赖中的应用方式。分子对接实验表明，polyP 可以与多种类型的 P2X 受体结合，其结合能类似于 ATP（ P2X 嘌呤受体的天然激动剂）。_{P2X 4}的进一步分子动力学模拟表明，一个聚 P 分子的结合会显着增加该受体通道对水分子的渗透性。因此，在这项研究中，我们首次证明polyP可以与胸腺细胞中的P2X受体相互作用并调节生理过程。