Defects in regulation of mitochondrial ATP synthase in cardiomyocytes from spontaneously hypertensive rats.
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.
Das
A M
AM
Department of Biochemistry, University of Oxford, United Kingdom.
Harris
D A
DA
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D008297:Male; D008929:Mitochondria, Heart / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology* / Q000648:ultrastructure; D006180:Proton-Translocating ATPases / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000255:Adenosine Triphosphate; D006180:Proton-Translocating ATPases; D002118:Calcium