Uptake and Release of N-Methyl-d-Aspartate by Rat Brain Slices

Abstract: The excitant amino acid, N -methyl- d -aspartate, was actively taken up by slices of rat cerebral cortex. This uptake was Na⁺ - and temperature-dependent, but was relatively inefficient (K_m 3 MM, V_max 0.07 μmol/g/min) compared with that of other acidic amino acids. The uptake of N -methyl- d -aspartate does not appear to have a rate-limiting influence on the time course of N -methyl- d -aspartate-induced excitation since potent uptake inhibitors, such as threo-3-hydroxy- l -aspartate, do not influence the excitant action of N -methyl- d -aspartate. The relatively prolonged excitant action of this acidic amino acid may be the result of relatively slow dissociation of the activated receptor complex. Reloaded N -methyl- d -aspartate can be released from rat brain slices by stimulation with K⁺ ions. Such K⁺-stimulated release appeared to be Ca²⁺-independent, unlike the K⁺-stimulated release of preloaded d -aspartate. These findings suggest that N -methyl- d -aspartate may be a weak but selective substrate for a glial acidic amino acid uptake system.