Department of Biophysics (M.U.) and Department of Pharmacology (O.U.), Faculty of Medicine, Ankara University, Ankara, Turkey
Department of Biophysics (M.U.) and Department of Pharmacology (O.U.), Faculty of Medicine, Ankara University, Ankara, Turkey.
Mol Pharmacol. 2019 Apr;95(4):442-450. doi: 10.1124/mol.118.115022. Epub 2019 Feb 8.
The ligand-gated ion channel P2X7 receptor attracts special attention due to its widespread presence as well as its unusual responses. Besides relatively well-understood mechanisms such as intracellular Ca increase and K depletion, the P2X7 receptor activates other peculiar responses whose mechanisms are not fully understood. The best known among these is the permeabilization of the cell membrane to large molecules. This permeabilization has been explained by the activation of a nonselective permeation pathway by the P2X7 receptor, a phenomenon called "pore formation." However, with the emergence of new data, it became apparent that large molecules enter the cell directly through the pore of the ion channel, similar to the smaller ions. This explanation seems to be true for cationic large molecules. On the other hand, there is still convincing evidence indicating that the P2X7 receptor activates a separate pathway that permeates anionic large molecules in some cell types. Furthermore, there exist functional data suggesting that the P2X7 receptor may also activate other intracellular signaling molecules or other ion channels. Interestingly and contrary to what is expected from a ligand-gated channel, these activations occur in a seemingly direct manner. Somewhat overshadowed by the pore formation hypothesis, these action mechanisms may lead to a better understanding of not only the P2X7 receptor itself but also some important physiologic functions such as the release of anionic autocoids/neurotransmitters in the central nervous system. This review discusses, assesses, and draws attention to the data concerning these neglected but potentially important points in the P2X7 receptor field.
配体门控离子通道 P2X7 受体因其广泛存在和异常反应而备受关注。除了相对了解的机制，如细胞内 Ca2+增加和 K+耗竭外，P2X7 受体还激活其他机制尚未完全了解的特殊反应。其中最著名的是细胞膜对大分子的通透性增加。这种通透性的增加是通过 P2X7 受体激活非选择性渗透途径来解释的，这种现象称为“孔形成”。然而，随着新数据的出现，很明显，大分子通过离子通道的孔直接进入细胞，类似于较小的离子。这种解释似乎适用于阳离子大分子。另一方面，仍有令人信服的证据表明，在某些细胞类型中，P2X7 受体激活一种独立的途径，使阴离子大分子渗透。此外，还有功能数据表明，P2X7 受体还可以激活其他细胞内信号分子或其他离子通道。有趣的是，与配体门控通道的预期相反，这些激活似乎是以直接的方式发生的。这些作用机制在某种程度上被孔形成假说所掩盖，但它们可能导致对 P2X7 受体本身以及一些重要生理功能（如中枢神经系统中阴离子自体活性物质/神经递质的释放）的更好理解。本文综述了这些被忽视但可能重要的 P2X7 受体领域的相关数据，并对其进行了评估和关注。
