Inhibition of rat brain mitochondrial calcium transport by chlordecone

Abstract

Assessment of 45Ca 2+ transport in rat brain mitochondria following in vitro and in vivo exposures to the neurotoxic insecticide chlordecone revealed a locus for chlordecone's mitochondrial impairment in the coupling reactions of oxidative phosphorylation. Mitochondrial 45Ca 2+ transport supported by either 2 m m succinate (free energy supplied via electron transport) or 800 μ m ATP (free energy supplied via the Mg 2+ ATPase reaction) was inhibited by low concentrations of chlordecone (10 −8–10 −5 m). Administration of a tremorigenic dose (40 mg/kg, po) of chlordecone to rats similarly inhibited both succinate- and ATP-supported 45Ca 2+ uptake in brain mitochondria in vitro. Studies on the subcellular distribution of [ 14C]chlordecone in rat brain following in vivo administrations were compared to those on the mitochondrial uptake of [ 14C]chlordecone in vitro. Administration of the 40-mg/kg tremorigenic dose of chlordecone produced mitochondrial chlordecone concentrations which were comparable to the tissue concentrations achieved by exposing mitochondria to a 2 × 10 −6 m concentration of chlordecone in vitro. These data lend further support for mitochondrial inhibition as a mechanism for chlordecone toxicity.