Substrate specific effects of calcium on the metabolism of rat
heart mitochondria.
Panov, Alexander V., and Russell C. Scaduto.
The Department of Cellular and Molecular Physiology, The Milton S.
Hershey Medical Center, The Pennsylvania State University, P.O. Box
850, Hershey, PA 17033
APStracts 2:0463H, 1995.
Oxidative metabolism in heart is tightly coupled to mechanical work.
Since this coupling process is believed to involve calcium, the roles
of mitochondrial calcium in the regulation of oxidative
phosphorylation was studied in isolated rat heart mitochondria. The
electrical component of the mitochondrial membrane potential (Dy) and
the redox state of the pyridine nucleotides were determined during
the oxidation of various substrates under different metabolic states.
In the absence of added adenine nucleotides, the NADP+ redox couple
was almost completely reduced, irrespective of the specific substrate
and the presence of Ca2+, whereas NAD+-couple redox state was highly
dependent on the substrate type and the presence of Ca2+. Titration
of respiration with ADP, in the presence of excess hexokinase and
glucose, showed that both respiration and NAD(P)+ reduction were very
sensitive to ADP. The Vmax of ADP-stimulated respiration Km values
for ADP were dependent on the particular substrate employed. Dy was
much less sensitive to ADP. With either [alpha]-ketoglutarate or
glutamate as substrate, Ca2+ significantly increased reduction of
NAD(P)+. Ca2+ did not influence NAD(P)+ reduction with either
acetylcarnitine or pyruvate as substrate. In the presence of ADP, Dy
was increased by Ca2+ at all metabolic states with either glutamate
plus malate, 0.5 mM [alpha]-ketoglutarate plus malate, or with
pyruvate plus malate as substrates. The data presented support the
hypothesis that cardiac respiration is controlled by the availability
of both calcium and ADP to mitochondria. The data indicate that an
increase in substrate supply to mitochondria can increase
mitochondrial respiration at given level of ADP. This effect can be
produced by calcium with substrates such as glutamate, with utilize
[alpha]-ketoglutarate dehydrogenase activity for oxidation. Increases
in respiration by calcium may mitigate an increase in ADP during
periods of increased cardiac work.
Received 10 January 1994; accepted in final form 25 September
1995.
APS Manuscript Number H25-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95