Glutamate Receptors Mediate Regulation of Na Pump Isoform Activities in Neurons

Rat cerebral neurons matured in culture were stimulated with glutamate analogues, and the K+ uptake activities of Na pump isoforms were measured. Ionotropic receptor agonists, kainate, AMPA, and NMDA, increased total K+ uptake activity via activation of the alpha2/alpha3 isoforms and an inhibition of the alpha1 isoform as reported previously for glutamate. The effects of kainate or AMPA were antagonized by CNQX and those of NMDA were by APV or MK-801. In contrast, metabotropic receptor agonist ACPD had no effects on the Na pump isoform activities. Glutamate transporter substrate, PDC, was effective, but NMDA receptor antagonists abolished the effects of PDC. These results suggest that the ionotropic glutamate receptors mediate the regulation of Na pump isoform activities in neurons.