REGULATION OF THE MITOCHONDRIAL ATP SYNTHASE IS DEFECTIVE IN RAT-HEART DURING ALCOHOL-INDUCED CARDIOMYOPATHY

Mitochondrial ATP synthase capacity was measured in cardiomyocytes fro m sucrose-fed (control) and alcohol-fed (cardiomyopathic) rats. Cells from alcohol-fed rats showed an ATP synthase capacity raised by 40% re lative to the control values of 1.8 mumol/min per mg cell protein. Cel ls from control rats were able to increase their ATP synthase capacity by up to 80% in response to increased energy demand. In contrast, cel ls from alcohol-fed rats had lost the ability to up-regulate their ATP synthase. Cells from control rats maintained their internal ATP level s at 38 nmol/mg cell protein before and after an increased energy dema nd. In cells from alcohol-fed rats, ATP levels fell by 20% after 2 min of increased energy demand. It was concluded that the inability of ce lls from alcohol-fed rats to maintain ATP levels was due to their redu ced ability to increase mitochondrial ATP synthase activity as energy demand is increased. Such ATP deficits may contribute to heart dysfunc tion in alcohol-induced cardiomyopathy.