AJP - Heart and Circulatory Physiology, Vol 259, Issue 4 1264-H1269, Copyright © 1990 by American Physiological Society
Defects in regulation of mitochondrial ATP synthase in cardiomyocytes from spontaneously hypertensive rats
A. M. Das and D. A. Harris
Department of Biochemistry, University of Oxford, United Kingdom.
Control of mitochondrial ATP synthase capacity was investigated in cultured
cardiomyocytes from normotensive (Wistar-Kyoto) and spontaneously
hypertensive (SHR) rats. The basal ATP synthase capacity in quiescent
cardiomyocytes was raised in the hypertensive rats (2.9 +/- 0.1
mumol.min-1.mg protein-1) compared with normotensive rats (2.2 +/- 0.1
mumol.min-1.mg-1). However, this high value is restored to normal after
treatment of the cells with verapamil or ruthenium red; agents that do not
affect ATP synthase capacity in normal cells. It is concluded that
abnormally high intramitochondrial Ca2+ levels, or an abnormal
mitochondrial response to Ca2+ concentration, are responsible for ATP
synthase activation in quiescent SHR cells. Cardiomyocytes from
normotensive rats respond to increased energy demand (caused by electrical
stimulation or treatment with positive inotropic agents) by increasing
their ATP synthase capacity up to twofold. Cells from SHR rats are unable
to control their ATP synthase in this way. It is concluded that some defect
in regulation of the mitochondrial ATP synthase occurs in myocytes from
hypertensive rats.
