Inhibition of CAMK II modulates water permeability by reducing AQP4 expression in astrocytes after oxygen-glucose deprivation.

The predominant form of edema that occurs during the early stage of ischemic stroke is cytotoxic, resulting in neuronal injury during brain ischemia and reperfusion. Intracellular calcium (Ca2+) is elevated following brain ischemia leading to increased cell membrane permeability. Ca2+/calmodulin-dependent protein kinase II (CaMK II), the downstream molecular signal of N-methyl-d-aspartate receptors (NMDARs), is sensitive to elevations in intracellular Ca2+. Aquaporin-4 (AQP4), which is expressed primarily in the brain, is a water-transport protein. However, it is unclear whether CaMK II regulates AQP4 expression to modulate cellular water permeability. We exposed cultured astrocytes to a hypoxic and glucose-free environment to mimic an ischemic environment in vitro. We investigated the effects of oxygen-glucose deprivation (OGD) on astrocytic viability and swelling, as well as CaMK II and AQP4 expression. We also studied the effects of CaMK II inhibition on cell swelling, viability and AQP4 expression. OGD increased astrocytic swelling and expression of CaMK II and AQP4, and it decreased astrocyte viability. Inhibition of CaMK II resulted in reduced astrocyte water permeability and AQP4 expression. We concluded that the upregulation of CaMK II promoted astrocyte swelling by increasing the expression of AQP4 after OGD.