Assentoft Mette, Larsen Brian Roland, MacAulay Nanna
Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, Bldg. 12.6, 2200, Copenhagen, Denmark.
Neurochem Res. 2015 Dec;40(12):2615-27. doi: 10.1007/s11064-015-1519-z. Epub 2015 Jan 29.
Aquaporin 4 (AQP4) is the predominant water channel in the mammalian brain and is mainly expressed in the perivascular glial endfeet at the brain-blood interface. Based on studies on AQP4(-/-) mice, AQP4 has been assigned physiological roles in stimulus-induced K(+) clearance, paravascular fluid flow, and brain edema formation. Conflicting data have been presented on the role of AQP4 in K(+) clearance and associated extracellular space shrinkage and on the stroke-induced alterations of AQP4 expression levels during edema formation, raising questions about the functional importance of AQP4 in these (patho)physiological aspects. Phosphorylation-dependent gating of AQP4 has been proposed as a regulatory mechanism for AQP4-mediated osmotic water transport. This paradigm was, however, recently challenged by experimental evidence and molecular dynamics simulations. Regulatory patterns and physiological roles for AQP4 thus remain to be fully explored.
水通道蛋白4（AQP4）是哺乳动物大脑中主要的水通道，主要表达于脑血界面的血管周围神经胶质终足。基于对AQP4基因敲除小鼠的研究，AQP4在刺激诱导的钾离子清除、血管周围液体流动和脑水肿形成中发挥生理作用。关于AQP4在钾离子清除及相关细胞外间隙收缩中的作用，以及在水肿形成过程中中风诱导的AQP4表达水平变化，存在相互矛盾的数据，这引发了关于AQP4在这些（病理）生理方面功能重要性的疑问。有人提出AQP4的磷酸化依赖性门控是AQP4介导的渗透性水转运的一种调节机制。然而，最近的实验证据和分子动力学模拟对这一范式提出了挑战。因此，AQP4的调节模式和生理作用仍有待充分探索。
