Dominant role of mitochondria in protection against a delayed neuronal Ca²⁺ overload induced by endogenous excitatory amino acids following a glutamate pulse

Abstract

The objective of this study was to evaluate the contribution of mitochondria to the clearance of Ca 2+ loads induced by glutamate or 25 mM K ÷ pulses. The mitochondrial Ca 2+ uptake was suppressed by application of 0.5 ttM antimycin A or 3-5 mM NaCN in combination with 2.5 Ixg/ml oligomycin. In most cells such treatments both in the presence and in the absence of external Na + failed to abolish the early fast phase of

The role of intracellular Na+ and mitochondria in buffering of kainate‐induced intracellular free Ca2+ changes in rat forebrain neurones

“…However, it is at present unclear which processes may be participating in this Ca¥ transport. Several previous studies have documented the role of mitochondria in buffering depolarization-or glutamateinduced [Ca¥]é changes in neurones (Thayer & Miller, 1990;Werth & Thayer, 1994;White & Reynolds, 1995;Kiedrowski & Costa, 1995;Wang & Thayer, 1996;Khodorov et al 1996). However, these previous studies have not explicitly documented the role of mitochondria in kainateinduced [Ca¥]é changes.…”

“…Previous studies that have focused on NMDA receptor-mediated Ca¥ loads have suggested that Ca¥ uptake by mitochondria is an important mechanism for buffering [Ca¥]é changes, and that mitochondria become progressively more important as the intensity of the stimulus increases (White & Reynolds, 1995, 1997Wang & Thayer, 1996;Khodorov, Pinelis, Storozhevykh, Vergun & Vinskaya, 1996). It has also become evident that mitochondrial Ca¥ loading shapes the recovery from increases in [Ca¥]é because the time necessary for [Ca¥]é to return to baseline following NMDA receptor activation is dominated by the Ca¥ release from the mitochondrial pool that is mediated by mitochondrial Na¤-Ca¥ exchange (Nicholls & Akerman, 1982;Kiedrowski & Costa, 1995;Wang & Thayer, 1996;White & Reynolds, 1997).…”

Early Mitochondrial Dysfunction after Cortical Contusion Injury

“…Neuronal survival is intimately linked to mitochondrial homeostasis. Mitochondria supply the central nervous system with energy (ATP), as well as regulating calcium within the cell (Khodorov et al, 1996). Several therapeutic interventions that target stabilizing mitochondria have shown promising results by reducing overall neuronal tissue damage as well as enhancing neurological outcome following TBI (Verweij et al, 1997;Sullivan et al, 1999;Sullivan et al, 2004;Hino et al, 2005;Xiong et al, 2005;Clark et al, 2007).…”

Role of Mitochondria in the Mechanisms of Glutamate Toxicity

“…Thus, mitochondrial membrane potential can be regarded as a factor contributing to intracellular Ca 2+ reg ulation in neurons, which definitely occurs during activa tion of Glu receptors. Khodorov et al [26] showed that antimycin, an inhibitor of the 3rd complex of the electron transport chain, combined with the inhibitor of ATP syn thase, oligomycin, significantly inhibits Ca 2+ uptake into mitochondria. The latest data show that Ca 2+ uptake into mitochondria depends on the degree of their association with cytoskeleton.…”