The present study was undertaken to assess whether the
protein and
mRNA expression levels of the glial
water channel aquaporin-4 (AQP4) undergo downregulation 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 hypotonic
dextrose i.p. and 8-deamino-arginine
vasopressin (
dDAVP) s.c. Semiquantitative 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, respectively. Similarly, immunoblots of cerebellar samples revealed an increase in AQP4 immunoreactivity to 136 +/- 6% (n = 6) and 218 +/- 44% (n = 6) of control levels, after 4 or 48 h of
hyponatremia. In contrast, AQP4
mRNA levels were unchanged after 4 h of severe
hyponatremia (104 +/- 14% of control levels; n = 17), indicating that there are no changes in AQP4 expression in response to systemic hypoosmolarity. Immunocytochemistry and high-resolution immunogold electron microscopy revealed highly polarized labeling of AQP4 in astrocyte end-feet surrounding capillaries and forming the glia limitans. This pattern of labeling was not changed whereas an increased labeling intensity of AQP4 could be observed in response to
hyponatremia. In conclusion,
hyponatremia causes a pronounced and rapid increase in AQP4 immunoreactivity that is not accompanied by any increase in AQP4
mRNA expression. The increased AQP4 immunosignal may reflect secondary conformational modifications of
AQP4 protein, leading to enhanced antibody binding. This post-translational modification of AQP4 may participate in the adaptation of cerebral tissue to systemic
hyponatremia.