The effect of 2,3-butanedione monoxime, verapamil and cardiac work
on the mitochondrial membrane potential in perfused rat hearts.
Doumen, Chris, Bang Wan, and Olga Ondrejickova.
Department of Cellular and Molecular Physiology, Milton S. Hershey
Medical Center, Pennsylvania State University, Hershey, Pa 17033
APStracts 2:0108H, 1995.
The biochemical link providing effective coordination between the
mitochondrial ATP synthetic machinery and the contractile apparatus
following transitions in cardiac work remains enigmatic. Studies were
designed to determine whether activation of the actomyosin ATPase is
a necessary part of the signaling mechanism to the mitochondrial ATP
synthase or whether a rise in cytosolic free Ca2+ is sufficient to
activate the synthase. Using Langendorff perfused rat hearts, cardiac
work was varied via changes in perfusion pressure and by the
inclusion of a [beta]-adrenergic agent. Furthermore, 2,3-butanedione
monoxime and verapamil were used to independently vary either the
activity of the actomyosin ATPase or the level of cytosolic free
Ca2+. Determinations of the in vivo Dym (Am.J. Physiol,
265:H445,1993) and its vectorial displacement during work transitions
provide valuable information concerning direct activation of the ATP
synthase and proton movement through the membrane domain of the
synthase. Increased cardiac work in the presence of the [beta]
-adrenergic agent resulted in a decrease in Dym. Addition of 2,3
-butanedione monoxime decreased cardiac work but did not change Dym.
The inclusion of verapamil resulted in similar decreases in cardiac
work. However Dym reversed back to a value observed under control,
low work conditions. These results in conjunction with data regarding
levels of high-energy phosphates, free Mg2+ and cAMP suggest a
calcium mediated increase in the activity of the ATP synthase.
Received 5 September 1994; accepted in final form 23 February
1995.
APS Manuscript Number H827-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 4 April 1995.