Calcium metabolism is affected by ischemia-reperfusion syndromes but the entire mechanism of this perturbation needs to be clarified15. Almost the entire intra-cellular calcium concentration is bound to phospholipids or proteins, or sequestered into the endoplasmatic reticulum, to calciosomes and mitochondria. In physiologic conditions, a very large electrochemical driving force tends to translocate calcium into cells. This force has two components: (1) a chemical gradient - intra-cellular calcium concentration being 104 lower than the extra-cellular concentration - and (2) an electrical gradient - the electrical potential across plasma membranes (the inside being 60-90 mV negative to the outside). It is clear that a coupling exists between influx of calcium into the cells and their production of reactive oxygen species. Mitochondrial calcium accumulation and oxidative stress can trigger the assembly of a high-conductance pore (i.e., MPT or mitochondrial permeability transition) in the inner mitochondrial membrane. This leads to a collapse of the electrochemical potential for H+, thereby arresting ATP production and triggering the generation of reactive oxygen species. During the hypoxic ischemia phase, calcium homeostasis is greatly affected, it starts activating phospholipases, endonucleases and proteases and it affects protein phosphorylation by altering the activity of protein kinases and phosphatases. Moreover, it activates enzymes that give rise to the production of reactive oxygen species and NO. For instance, the intracellular calcium concentration activates proteases permitting the conversion of xanthine dehydrogenase (d-form) to xanthine oxydase (o-form) with the formation of free radicals during reperfusion and re-oxygenation.
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