Mitochondrial membrane potential and the permeability transition in excitotoxicity.
Acute neuronal injury caused by activation of glutamate receptors in neurons, or excitotoxicity, can be triggered by the activation of N-methyl-D-aspartate receptors and the entry of large amounts of Ca2+. Recent studies have suggested that mitochondria have a critical role in the excitotoxicity injury mechanism. Mitochondria accumulate large amounts of Ca2+ following glutamate stimulation, and also generate reactive oxygen species. Moreover, the prevention of mitochondrial Ca2+ accumulation protects neurons from injury. The target for the actions of Ca2+ in the mitochondrial matrix has not yet been established. The permeability transition pore has the characteristics of a mechanism that is well suited to mediate neuronal injury. However, evidence for activation of the permeability transition pore in intact neurons is rather indirect, and these data suffer from some ambiguities that make it difficult to conclude that permeability transition is a critical contributor to mitochondrially mediated neuronal injury.
Reynolds
I J
IJ
Department of Pharmacology, University of Pittsburgh, Pennsylvania 15261, USA. iannmda@pop.pitt.edu
D000818:Animals; D001921:Brain / Q000502:physiology* / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D018698:Glutamic Acid / Q000494:pharmacology*; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D009498:Neurotoxins / Q000494:pharmacology*; D010539:Permeability
D009498:Neurotoxins; D018698:Glutamic Acid; D002118:Calcium