Mechanism(s) of altered mitochondrial calcium transport in acutely ischemic canine hearts.
Studies were undertaken to determine the mechanisms leading to altered mitochondrial function in ischemic myocardium. A new procedure has been developed to routinely isolate 60-70% of the total mitochondrial protein from heart tissue. After 1 hour of ischemia, mitochondria exhibit decreases of more than 50% in phosphorylating respiration for both NADH- and succinate-linked substrates compared to controls. However, no significant decreases in the efficiency of mitochondrial ATP synthesis (ADP:0) or ATPase activity are observed. Rates of substrate-driven Ca2+ uptake exhibit decreases greater than that seen with phosphorylating respiration with incomplete uptake and premature release of Ca2+. Spectrophotometric measurements in ischemic heart reveal rapid oxidation or loss of mitochondrial NADH with marked "swelling" of the inner membrane compartment; both changes parallel the loss of Ca2+. Significant losses in intramitochondrial adenine nucleotides also are found. Mitochondrial retention of accumulated Ca2+ can be restored by addition of small amounts of exogenous adenine nucleotides (ATP or ADP) with concomitant attenuation of both NADH oxidation and "swelling." The data indicate that, following 1 hour of ischemia, the efficiency of mitochondrial ATP production is still relatively intact whereas both electron transport chain activity and calcium transport are severely compromised. These decreases appear to be related to selective membrane damage in the mitochondrial inner membrane.
D000208:Acute Disease; D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D003327:Coronary Disease / Q000378:metabolism*; D004285:Dogs; D003576:Electron Transport Complex IV / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism; D008929:Mitochondria, Heart / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D009243:NAD; D013386:Succinates
D013386:Succinates; D009243:NAD; D003576:Electron Transport Complex IV; D008274:Magnesium; D002118:Calcium