RESPIRATORY CONTROL IN HEART-MUSCLE DURING FATTY-ACID OXIDATION - ENERGY-STATE OR SUBSTRATE-LEVEL REGULATION BY CA2+

Fatty acids are the main fuel for the myocardium in vivo. They increas e oxygen consumption, but the regulation of their beta-oxidation is no t well known, Since Ca2+ and matrix volume have been implicated in the regulation of fatty acid oxidation in liver mitochondria, we set out to investigate the effects of Ca2+ on cellular respiration and energet ics in the isolated perfused rat heart when oxidizing a short-chain fa tty acid. Infusion of hexanoate increased oxygen consumption, while st epwise changes in the perfusate Ca2+ concentration in the range 0.5-2. 5 mM caused the mechanical work output and oxygen consumption to chang e in parallel, Hexanoate addition increased the cellular energy state as determined by P-31 NMR and evaluated from the cytosolic [ATP]/[ADP] .[Pi] ratio. During fatty acid infusion the energy state decreased sli ghtly upon Ca2+-induced inotropy, and after discontinuation of the hex anoate infusion the de-energization was more pronounced. The fatty aci d caused an extensive partially reversible reduction of navoproteins a nd NAD with a slight tendency for oxidation during Ca2+-induced inotro py. The data are in agreement with the notion that oxygen consumption during fatty acid oxidation is mainly determined by the energy expendi ture, even in the presence of Ca2+-induced alterations in the inotropi c state, The constancy of the redox states of mitochondrial flavins an d NADH/NAD during large changes in oxygen consumption is interpreted a s indicating stabilization of the mitochondrial redox states by Ca2+-l inked regulation. (C) 1995 Academic Press Limited.