LONIDAMINE-MEDIATED RESPIRATORY CHANGES IN RAT-HEART MYOCYTES - A REEXAMINATION OF THE FUNCTIONAL-RESPONSE OF MITOCHONDRIAL CYTOCHROME-C-OXIDASE

Respiratory activity of intact cardiac myocytes isolated from rats tre ated with lonidamine (LND) has bee examined under conditions where cyt ochrome oxidase turns over at its maximal rate. Compared to myocytes i solated from control rat hears, those treated with LND displayed a 60% increase in the cytochrome oxidase-dependent rate of respiration; ele ctron microscopy revealed, in agreement with the literature, that the membrane structure of the mitochondrion had become disorganized. The i ncrease in the rate of oxygen consumption was correlated with the (par tial) impairment of the membrane ability to maintain the proton electr ochemical potential gradient which normally inhibits oxidase activity. Results are discussed with reference to previous reports showing no e ffect of LND on cytochrome c oxidase activity. The evidence reported b etter clarifies the contribution of cytochrome oxidase to the demonstr ated energetic failure displayed by cells treated with LND.