Increased aquaporin-4 immunoreactivity in rat brain in response to systemic hyponatremia

The present study was undertaken to assess whether the protein and mRNA exp ression levels of the glial water channel aquaporin-4 (AQP4) undergo downre gulation and whether there is a subcellular redistribution of AQP4 protein in rat brain in response to systemic hyponatremia and brain edema. Systemic hyponatremia was induced for 4 or 48 h by combined administration of hypot onic dextrose i.p. and 8-deamino-arginine vasopressin (dDAVP) s.c. Semiquan titative immunoblotting of membrane enriched fractions showed significantly increased immunoreactivity to 164 +/- 12% (n = 6) and 153 +/- 12% (n = 6) of control levels in brain after 4 or 48 h of systemic hyponatremia, respec tively. Similarly, immunoblots of cerebellar samples revealed an increase i n AQP4 immunoreactivity to 136 +/- 6% (n = 6) and 218 +/- 44% (n = 6) of co ntrol levels, after 4 or 48 h of hyponatremia. In contrast, AQP4 mRNA level s were unchanged after 4 h of severe hyponatremia (104 +/- 14% of control l evels; n = 17), indicating that there are no changes in AQP4 expression in response to systemic hypoosmolarity. Immunocytochemistry and high-resolutio n immunogold electron microscopy revealed highly polarized labeling of AQP4 in astrocyte end-feet surrounding capillaries and forming the glia limitan s, This pattern of labeling was not changed whereas an increased labeling i ntensity of AQP4 could be observed in response to hyponatremia. In conclusi on, hyponatremia causes a pronounced and rapid increase in AQP4 immunoreact ivity that is not accompanied by any increase in AQP4 mRNA expression. The increased AQP4 immunosignal may reflect secondary conformational modificati ons of AQP4 protein.