title: The role of Ca2+ in the regulation of intramitochondrial energy production in heart.
abstract: In the heart and other mammalian tissues, there are three exclusively intramitochondrial dehydrogenases that occupy key sites in oxidative metabolism which can be activated by increases in Ca2+ in the range 0.1-10 microM. They are the pyruvate, NAD+-isocitrate and 2-oxoglutarate dehydrogenases. Activation of these enzymes can be demonstrated within intact mitochondria (incubated with Na+ and Mg2+) when extramitochondrial Ca2+ is raised within the expected physiological range (0.05-5 microM). Evidence is presented to suggest that the increase in cytoplasmic [Ca2+] caused by positive inotropic agents in the heart result in increases in intramitochondrial [Ca2+] and activation of the dehydrogenases and hence oxidative energy metabolism. Therefore it is proposed that the main function of the mitochondrial Ca2+-transport system is to regulate matrix rather than cytoplasmic Ca2+. In this way the stimulation of energy utilisation as contraction is enhanced is balanced by a parallel stimulation of ATP producing reactions.
authors.affiliation: Department of Biochemistry, University of Leeds, U.K.
authors.forename: J G
authors.initials: JG
authors.lastname: McCormack
authors.forename: R M
authors.initials: RM
authors.lastname: Denton
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects; D066298:In Vitro Techniques; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D010088:Oxidoreductases; D002118:Calcium