The real kinetics of the mitochondrial calcium uniporter of the liver and its role in cell calcium regulation.

The activity of the calcium uniporter of rat liver mitochondria, allosterically enhanced by a pulse of calcium, decreases with time and in dependence on extramitochondrial Ca2+ concentration. Therefore, the initial velocity of calcium uptake by mitochondria depends on the extramitochondrial Ca2+ concentration prior to uptake. The allosteric activation by calcium and the hysteretic behaviour of the uniporter are the reasons why the course of calcium distribution between mitochondria and extramitochondrial space is determined for many minutes by the initial extramitochondrial Ca2+ concentration. This dependence and also the independence on the intramitochondrial calcium content are shown in an in vitro system, simulating conditions prevailing in vivo during the action of alpha-adrenergic agonists or vasoactive peptides on liver and during the early phase of carbon tetrachloride intoxication.