INTERACTION BETWEEN NEURONAL Na+, K+-ATPase AND NMDA RECEPTOR

M. G. BERSIER; G. RODRÍGUEZ DE LORES ARNAIZ

Buenos Aires

Congreso; XXXIX Reunion Anual de la Asociacion Argentina de Farmacologia Experimental (SAFE); 2007

Asociacion Argentina de Farmacologia Experimental (SAFE)

Ouabain increases the activated population of NMDA receptors. The participation of NMDA receptor in the ouabain neurotoxic effect has been suggested. Herein the effect of ouabain on the expression of NMDA subunits and Na+, K+-ATPase alfa3 subunit, as well as on the activity of neuronal Na+, K+-ATPase was evaluated. Wistar rats of 250 g were administered via i.c.v. with 1 microliter 10 mM ouabain or saline solution (control). Two days later, membranes of cerebral cortex and hippocampus were isolated. Western blots with antibodies for the NMDA receptor subunits: NR1; NR2A; NR2B; NR2C and NR2D and with the specific antibody for Na+, K+-ATPase subunit alfa3 were carried out. Na+, K+-ATPase activity was measured in synaptosomal membranes. The treatment produced the following changes: subunits NR2B and NR2C diminished in cerebral cortex and hippocampus, NR2A decreased only in hippocampus, whereas subunit NR1 did not changed in the studied areas. NR2D increased in cerebral cortex, but remained unaltered in hippocampus. Na+, K+-ATPase alfa3 subunit increased in cerebral cortex whereas Na+, K+-ATPase activity diminished 50%. It is concluded that ouabain administration led to a differential decrease in the expression of NMDA subunits. These results may be correlated with the modulatory action of ouabain on NMDA receptor. Enhancement of Na+, K+-ATPase alfa3 subunit may be a compensatory response to the inhibition of the Na+, K+-ATPase activity induced by ouabain.