Pb2+-mediated down-regulation of dihydropyridine receptors in skeletal muscle

This study examines the influence of chronic treatment with inorganic lead (Pb(2+)) on the presence of dihydropyridine receptors in two types of excitable cells, primary cultures of skeletal muscle and neural retina from embryonic chick. As assessed through binding of the dihydropyridine antagonist [3H] PN 200-110, treatment of skeletal muscle cultures with Pb2+ caused measurable reductions in the numbers of dihydropyridine receptors. The reductions were dose-dependent, requiring concentrations greater than 1microM, slow in onset, requiring incubation times greater than 12h, and tissue specific, being pronounced in skeletal muscle but absent from neural retina. The reduction in dihydropyridine receptors is attributable to enhanced rates of receptor degradation or reductions in biosynthesis, without activation or inhibition of protein kinase C, and are discussed with respect to the role of dihydropyridine receptors in excitation-contraction coupling.