The role of Ca2+ in the regulation of intramitochondrial energy production in heart.

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.