Figure 1.

Schematic of AQP4 subcellular mislocalization. (A) After neuronal activation, water enters astrocytes (along with other ions and neurotransmitters such as K+ and glutamate). Water is then transported into nearby blood vessels via perivascular AQP4, overall maintaining water homeostasis. (B) During epilepsy, perivascular AQP4 (M23-AQP4) is lost due to loss of its anchoring protein α-syntrophin (not shown). Additionally, the rapid influx of water activates vasopressin receptors leading to phosphorylation of AQP4 by PKC followed by internalization and subsequent degradation of AQP4. Swelling of astrocytes occurs, resulting in impaired cell volume regulation and further increasing neuronal hyperexcitability.