Key Players in Astrocyte Regulatory Volume Reduction (RVD): VRAC and Aquaporin

Astrocytes play important roles in maintaining the homeostasis of brain, including the maintenance of brain's water balance. However, under various diseases such as ischemic stroke, astrocytes are the first to show significant cellular edema, which in turn promotes the development of cerebral edema and aggravates brain injury. Regulatory volume reduction (RVD) is a compensatory response of astrocytes to rapidly reduce part of their volume in the face of fast swelling. Recent advances have revealed that volume-regulated anion channel (VRAC) and aquaporin (AQP) are key players in the RVD process. VRAC is a heteromers composed of members of the LRRC8 family. During astrocyte fast swelling, VRAC is activated and mediates the rapid transport of anions and organic osmolytes to extracellular space, which is the main driver of RVD. AQP, a six-transmembrane protein, is a selective bidirectional water channel, which is the structural basis for rapid cellular edema in astrocytes and is also the "fast track" for water transport to the extracellular compartment during RVD. Further understanding of the structure and function of VRAC and AQP and their roles in RVD will help to finally understand the mechanism of astrocyte RVD and provide potential targets for the treatment of brain edema.