THERMOREGULATORY UNCOUPLING IN HEART-MUSCLE MITOCHONDRIA - INVOLVEMENT OF THE ATP ADP ANTIPORTER AND UNCOUPLING PROTEIN/

Possible involvement of the ATP/ADP antiporter and uncoupling protein (UCP) in thermoregulatory uncoupling of oxidative phosphorylation in h eart muscle has been studied. To this end, effects of carboxyatractyla te (cAtr) and GDP, specific inhibitors of the antiporter and UCP, on t he membrane potential of the oligomycin-treated mitochondria from cold -exposed (6 degrees C, 48 h) and control rats have been measured. It i s found that cAtr increases the membrane potential level in both cold- exposed and non-exposed groups, the effect being strongly enhanced by cooling. As for GDP, it is effective only in mitochondria from the col d-exposed rats. In these mitochondria, the coupling effect of GDP is s maller than that of cAtr, CDP, which does not interact with UCP, is wi thout any influence on membrane potential. The cold exposure is found to increase the uncoupling efficiency of added natural (palmitate) or artificial (SF6847) uncouplers, the increase being cAtr- and GDP-sensi tive in the case of palmitate, The fatty acid-free bovine serum albumi n enhances Delta Psi in both cold-exposed and control groups, the effe ct being much larger in the former case. It is concluded that in heart muscle mitochondria the ATP/ADP antiporter is responsible for the 'mi ld uncoupling' under normal conditions and for major portion of the th ermoregulatory uncoupling in the cold whereas the rest of thermoregula tory uncoupling is served by UCP (presumably by UCP2 since the UCP2 mR NA level is shown to strongly increase in rat heart muscle under the c old exposure conditions used). (C) 1998 Federation of European Biochem ical Societies.