Effect of glutamate receptor ligands on mitochondrial membrane potential in rat dissociated cerebellar cells

The effect of three different glutamate receptor ligands on mitochondrial membrane potential has been studied in rat pup dissociated cerebellar cells by measuring rhodamine 123 fluorescence. L-glutamate, NMDA (N-methyl-D-aspartate) and kainate (from 10(-8) to 10(-3) M) decreased in a concentration-dependent manner the mitochondrial membrane potential with EC50 values of 6.7 +/- 1.7, 3.8 +/- 0.5, and 37.4 +/- 14 microM, respectively. Dizocilpine ((+)MK 801) was able to inhibit the NMDA- and L-glutamate-induced decrease in rhodamine 123 fluorescence, while kainate-induced fluorescence-decreases were unaffected. However, 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX) totally prevented the effect of kainate on mitochondrial membrane potential, but failed to block the L-glutamate effect. It is concluded that, in our cell preparation, L-glutamate exerts its action mainly through NMDA-subtype receptors, and that Ca2+ and Na+ entry through ionotropic glutamate receptors could be responsible for an impairment of mitochondrial membrane potential.