The effect of lead on the calcium-handling capacity of rat heart mitochondria.
1. Very low concentrations of Pb2+ decrease the capacity of rat heart mitochondria, oxidizing pyruvate plus malate, to remove Ca2+ from the medium. 2. The primary effect is on the rate of Ca2+ sequestration; this is reflected in the overall extent of Ca2+ removal. 3. Pb2+ has at least two separate actions. Below about 0.5 nmol/mg of protein, it acts solely by competing with Ca2+ (Ki = 0.4 muM); above this concentration it also inhibits the production or use of respiratory energy, so that at 1 nmol of Pb2+/mg of protein, Ca2+ removal is almost completely abolished. 4. Pb2+ inhibits coupled and uncoupled respiratory O2 use by mitochondria oxidizing pyruvate plus malate, but at higher concentrations than those that affect Ca2+ removal; similar concentrations of Pb2+ inhibit pyruvate uptake, but not malate uptake, by the mitochondria. 5. Mg2+ only decreases Ca2+ removal by competition, and is a far-less effective competitor than Pb2+ (Ki = 0.15 mM). It is possible that the primary cause of the second effect of Pb2+ is displacement of membrane Mg2+. 6. The consequences of these results are discussed in terms of the possible involvement of heart mitochondria in excitation-contraction coupling, and the Pb2+ levels that might occur in heart tissue in vivo.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005260:Female; D007700:Kinetics; D007854:Lead / Q000494:pharmacology*; D008274:Magnesium / Q000494:pharmacology; D008293:Malates / Q000378:metabolism; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D011773:Pyruvates / Q000378:metabolism; D051381:Rats
D008293:Malates; D011773:Pyruvates; D007854:Lead; D000255:Adenosine Triphosphate; D008274:Magnesium; D002118:Calcium