Noradrenaline effects on pyruvate decarboxylation: correlation with calcium signaling

Noradrenaline effects on the rate of metabolism of pyruvate to acetyl coenzyme A, catalyzed by the pyruvate dehydrogenase complex, was measured in primary cultures of mouse astrocytes as rate of production of labeled CO(2) from 1-[(14) C]pyruvate in the absence of competing glucose in the medium. The subtype specificity of a noradrenaline-stimulated increase in rate of CO(2) formation was identical to that for noradrenaline-induced increase in free intracellular calcium ([Ca(2+)](i)), suggesting a causal relationship between these two phenomena. The noradrenaline-induced stimulation of pyruvate decarboxylation was abolished in the presence of 10 mM magnesium chloride in the medium, combined with the omission of calcium, a procedure known to prevent an increased [Ca(2+)] in the cytosol from raising intramitochondrial [Ca(2+)]. Thus, the stimulation of metabolic flux through the reaction catalyzed by the pyruvate dehydrogenase complex appears to result from an increase in intramitochondrial [Ca(2+)] ions in astrocytes. Such a mechanism for stimulation of the same enzyme has been convincingly demonstrated in other cell types, primarily heart muscle and hepatic cells, but it has not previously been demonstrated in any cell type from the central nervous system.