title: Ca2+ ions, an allosteric activator of calcium uptake in rat liver mitochondria.
abstract: In a previous investigation, I have shown that the kinetics of the Ca uniporter change fundamentally when mitochondria have transitorily lost their membrane potential. The sigmoidal kinetics, usually observed in liver mitochondria, became almost hyperbolic. This means an increase in the affinity for calcium, and hence a considerable acceleration of Ca uptake in the range of low, e.g., physiological calcium concentration. In this investigation I show that extramitochondrial calcium released from the deenergized mitochondria causes the allosteric activation of the Ca uniporter. The dependence of the allosterical activation on the extramitochondrial Ca2+ concentration and on time is described. It is also reported that it is possible to activate allosterically the Ca uniporter of energized mitochondria by a short-term elevation of the extramitochondrial Ca2+ concentration. The process of activation is reversible. It is quickly reversed by the addition of chelators for Ca2+, and it is slowly reversed when the activating Ca2+ has to be removed by the mitochondrial Ca uniporter, though the bulk of extramitochondrial calcium is taken up by it very quickly. Several kinetics of the Ca uniporter are described. The implications of continually changing kinetics of the Ca uniporter are considered for carbon tetrachloride intoxication and the action of alpha 1-adrenergic agonists in liver cells.
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001711:Biotransformation / Q000187:drug effects; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels; D002135:Calcium-Binding Proteins / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D008930:Mitochondria, Liver / Q000378:metabolism*; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D012402:Rotenone / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D002135:Calcium-Binding Proteins; C034703:mitochondrial calcium uniporter; D012402:Rotenone; C051128:2,2-dimethylnitrilotriacetate; D009571:Nitrilotriacetic Acid; D002118:Calcium