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 Pb2+ during incubation in vitro; Pb2+ was also shown to enter mitochondria within the slices. The uptake of Pb2+ by isolated mitochondria was inhibited by N-3, La3+ 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 microM and inhibition ensued at higher concentrations. A substantial inhibitor-resistant component of Pb2+ uptake was noted, especially at medium Pb2+ concentrations greater than 25 microM, 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 degree in medium with various concentrations of Pb2+ showed two fractions of uptake, one saturating at 50-100 microM external Pb2+ and the other at 150-200 microM. Subsequent incubation for 60 min at 25 degrees led to further uptake at all concentrations. Upon isolation of mitochondria from incubated slices, significant amounts of Pb2+ were detected in the mitochondria within 5 min of addition of Pb2+ (200 microM), with maximum attained at 30 min. Electron microscopy of slices showed electron-dense particles, apparently of Pb2+, in the cortical cells but the greatest concentration was deposited in the basement membranes. The results indicate the importance of the basement membrane in limiting access of Pb2+ to cortical cells, and of mitochondria in accumulating Pb2+ once it is in the cells. They also illustrate the importance of interactions between Pb2+ and Ca2+.