Uptake of inorganic lead in vitro by isolated mitochondria and tissue slices of rat renal cortex

Slices of rat renal cortex were shown to take up Pb 2+ during incubation in vitro; Pb 2+ was also shown to enter mitochondria within the slices. The uptake of Pb 2+ by isolated mitochondria was inhibited by N 3 −, La 3+ and ruthenium red. A steady state of uptake was attained within 60 sec. The concentration dependence of uptake was complex; maximum uptake was attained at 25 μM and inhibition ensued at higher concentrations. A substantial inhibitor-resistant component of Pb 2+ uptake was noted, especially at medium Pb 2+ concentrations greater than 25 μM, and these concentrations also inhibited respiration state 3. The effects on respiration were reduced if the mitochondria had been preincubated with ruthenium red. Slices of renal cortex incubated at 1° in medium with various concentrations of Pb 2+ showed two fractions of uptake, one saturating at 50–100 μM external Pb 2+ and the other at 150–200 μM. Subsequent incubation for 60 min at 25° led to further uptake at all concentrations. Upon isolation of mitochondria from incubated slices, significant amounts of Pb 2+ were detected in the mitochondria within 5 min of addition of Pb 2+ (200 μM), with maximum attained at 30 min. Electron microscopy of slices showed electron-dense particles, apparently of Pb 2+, in the cortical cells but the greatest concentrations was deposited in the basement membranes. The results indicate the importance of the basement membrane in limiting access of Pb 2+ to cortical cells, and of mitochondria in accumulating Pb 2+ once it is in the cells. They also illustrate the importance of interactions between Pb 2+ and Ca 2+.