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Flow cytometric study of mitochondrial dysfunction after AMPA receptor activation

Abstract:

The effect of AMPA-receptor stimulation on MMP and on the concentration of intracellular calcium ([Ca2+](i)) was studied in dissociated CGC from rat pups, by flow cytometry. In the presence of cyclothiazide, AMPA induced a sodium-independent decrease in MMP up to 30.7 ± 2.5%. This effect was antagonized by CNQX and NBQX. Mepacrine and dibucaine reversed the effect of AMPA on MMP, suggesting that it is mediated by a release of arachidonic acid. AMPA alone induced a slight (about 7%) increase 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 observed 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 AMPA receptors. It is concluded that when AMPA-receptor desensitization is blocked, a decrease in MMP and an increase in [Ca2+](i) occurs, which could be additional events to potentiate neuronal cell death induced by glutamate.