Direct exposure to N-methyl-d-aspartate alters mitochondrial function

N-methyl-d-aspartate (NMDA) receptors have long been known to be associated with the plasma membrane, providing a channel for the passage of extracellular Ca(2+) into the cytosol during synaptic transmission. Recent results from our laboratory indicate that in addition to this classic location, an NMDA-sensitive site (NMDAm) may also exist within the inner mitochondrial membrane. We report direct exposure of mitochondrial to NMDA enhances the production of reactive oxygen species and attenuate ROS-induced cytochrome c release, all the while slowing the rate of Ca(2+)-induced mitochondrial swelling. Treatment with NMDA did not alter the mitochondrial membrane potential. The findings of this study lend further support for the existence of NMDAm and suggest that this site may serve to stabilize mitochondrial function.