Chlordecone inhibition of calmodulin activated calcium ATPase in rat brain synaptosomes

The effect of chlordecone on Ca2+-ATPase of rat brain synaptosomes in the absence and presence of calmodulin was determined in vitro and in vivo. A 50% activation of Ca2+-ATPase was obtained at 5 micrograms calmodulin per 1.5 ml reaction mixture containing 50 micrograms synaptosomal protein. Chlordecone inhibited Ca2+-ATPase in the absence of calmodulin with an IC50 of 10 microM, whereas chlordecone at 1.0 microM, which had no effect on the basal enzyme activity, completely inhibited the calmodulin activated Ca2+-ATPase. Chlordecone-treated rats showed a significant reduction in calmodulin levels in brain P2 fraction. Brain synaptosomal Ca2+-ATPase in chlordecone-treated rats showed a 50% reduction, which was restored by exogenously added calmodulin. These results suggest that chlordecone may be altering calmodulin-regulated synaptic processes in the brain.