Mitochondrial response to calcium in the developing brain.
Developmental differences in mitochondrial content and metabolic enzyme activities have been defined, but less is understood about the responses of brain mitochondria to stressful stimuli during development. Cerebral mitochondrial response to high Ca(2+) loads after brain injury is a critical determinant of neuronal outcome. Brain mitochondria isolated from 16-18-day-old rats had lower maximal, respiration-dependent Ca(2+) uptake capacity than brain mitochondria isolated from adult rats in the presence of ATP at both a pH of 7.0 and 6.5. However, in the absence of ATP, immature brain mitochondria exhibited greater Ca(2+) uptake capacity at pH 7.0 and 6.5, indicating a greater resistance of immature brain mitochondria to Ca(2+)-induced dysfunction under conditions relevant to those that exist during acute ischemic and traumatic brain injury. Acidosis reduced the maximal Ca(2+) uptake capacity in both immature and adult brain mitochondria. Cytochrome c was released from both immature and adult brain mitochondria in response to Ca(2+) exposure, but was not affected by cyclosporin A, an inhibitor of the mitochondrial membrane permeability transition. Developmental changes in mitochondrial response to Ca(2+) loads may have important implications in the pathobiology of brain injury to the developing brain.
Robertson
Courtney L
CL
Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. croberts@peds.umaryland.edu
Bucci
Cynthia J
CJ
Fiskum
Gary
G
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western / Q000379:methods; D002118:Calcium / Q000502:physiology*; D016572:Cyclosporine / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D016548:Prosencephalon / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D051381:Rats
D004791:Enzyme Inhibitors; D016572:Cyclosporine; D000255:Adenosine Triphosphate; D045304:Cytochromes c; D002118:Calcium