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.