FLOW CYTOMETRIC STUDY OF MITOCHONDRIAL DYSFUNCTION AFTER AMPA RECEPTOR ACTIVATION

The effect of AMPA-receptor stimulation on MMP and on the concentratio n of intracellular calcium ([Ca2+](i)) was studied in dissociated CGC from rat pups, by flow cytometry, In the presence of cyclothiazide, AM PA induced a sodium-independent decrease in MMP up to 30.7 +/- 2.5%, T his effect was antagonized by CNQX and NBQX, Mepacrine and dibucaine r eversed the effect of AMPA on MMP, suggesting that it is mediated by a release of arachidonic acid, AMPA alone induced a slight (about 7%) i ncrease in [Ca2+](i), In the presence of cyclothiazide, AMPA induced a concentration-dependent [Ca2+](i) increase up to 29.10 +/- 2.10% that was not reversed by flunarizine, This increase was similar to that ob served in a Na+-free medium, and was antagonized by CNQX and NBQX, but not by MK-801. Mitochondria play a key role in the modulation of [Ca2 +](i) since a significant [Ca2+](i) increase was found in the presence of FCCP, On the other hand, the dantrolene-sensitive calcium pools do not participate in the [Ca2+](i) increase induced by stimulation of A MPA receptors, It is concluded that when AMPA-receptor desensitization is blocked, a decrease in MMP and an increase in [Ca2+](i) occurs, wh ich could be additional events to potentiate neuronal cell death induc ed by glutamate, (C) 1998 Wiley-Liss,Inc.