title: Brain mitochondrial calcium transport: Origins of the set-point concept and its application to physiology and pathology.
abstract: The transport of calcium across the inner mitochondrial membrane plays a key role in neuronal physiology and pathology. The kinetic responses of the uniporter and efflux pathways are such that a cytosolic free calcium 'set-point' can be established - above which there is net calcium accumulation into the matrix that is reversed when plasma membrane transport lowers cytosolic calcium. Pathological activation of N-methyl-d-aspartate receptor mediated sodium and calcium entry into the neuron, as occurs in stroke and spreading depression, places severe demands on both the ATP-generating and calcium loading capacities of the neuronal mitochondria as the set-point is exceeded. Experiments that led to the concept of the set-point are reviewed.
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Bld., Novato, CA 94945, United States. Electronic address: dnicholls@buckinstitute.org.
authors.forename: David G
authors.initials: DG
authors.lastname: Nicholls
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D006801:Humans; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000378:metabolism
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D002118:Calcium
keywords: Brain; Calcium; Excitotoxicity; Mitochondria; Set-point