Dehydrogenase Activation by Ca2+ in Cells and Tissues

The activation of intramitochondrial dehydrogenases by Ca2+ provides a link between the intensity of work performance by a tissue and the activity of pyruvate dehydrogenase and the tricarboxylate cycle, and hence the rate of ATP production by the mitochondria. Several aspects of this model of the control of oxidative phosphorylation are examined in this article, with particular emphasis on mitochondrial functioning in situ in cardiac myocytes and in the intact heart. Recent use of the fluorescent Ca2+ chelating agents indo-1 and fura-2 has allowed a more quantitative description of the dependence of dehydrogenase activity upon concentration of free intramitochondrial Ca2+, in experiments with isolated mitochondria. Further, a novel technique developed by Miyata et al. has allowed description of free intramitochondrial Ca2+ within a single cardiac myocyte, and the conclusion that this parameter changes in response to electrical excitation of the cell over a range which would be expected to give substantial modulation of dehydrogenase activity.