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

Abstract:

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 μM, 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.