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Ischemia‐Induced Inhibition of Calcium Uptake into Rat Brain Microsomes Mediated by Mg 2+ /Ca 2+ ATPase
Author(s) -
Parsons J. T.,
Churn S. B.,
DeLorenzo R. J.
Publication year - 1997
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1997.68031124.x
Subject(s) - calcium , endoplasmic reticulum , microsome , calcium atpase , ischemia , calcium in biology , calcium metabolism , atpase , homeostasis , chemistry , biochemistry , endocrinology , medicine , biology , enzyme
It is well established that ischemia is associated with prolonged increases in neuronal intracellular free calcium levels. Recent data suggest that regulation of calcium uptake and release from the endoplasmic reticulum is important in maintaining calcium homeostasis. The endoplasmic reticulum Mg 2+ /Ca 2+ ATPase is the major mechanism for sequestering calcium in this organelle. Inhibition of this enzyme may play a causal role in the loss of calcium homeostasis. In order to investigate the effect of ischemia on calcium sequestration into the endoplasmic reticulum, microsomes were isolated from control and ischemic whole brain homogenates by differential centrifugation. Calcium uptake was measured by radioactive calcium ( 45 Ca 2+ ) accumulation in the microsomes mediated by Mg 2+ /Ca 2+ ATPase. Ischemia caused a statistically significant inhibition of presteady‐state and steady‐state calcium uptake. Duration of ischemia was directly proportional to the degree of inhibition. Decreased calcium uptake was shown not to be the result of increased calcium release from ischemic compared with control microsomes nor the result of selective isolation of ischemic microsomes from the homogenate with a decreased capacity for calcium uptake. The data demonstrate that ischemia inhibits the ability of brain microsomes to sequester calcium and suggest that loss of calcium homeostasis is due, in part, to ischemia‐induced inhibition of endoplasmic reticulum Mg 2+ /Ca 2+ ATPase.