Chlordecone inhibition of calmodulin activated calcium ATPase in rat brain synaptosomes

Abstract

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 μg calmodulin per 1.5 ml reaction mixture containing 50 μg synaptosomal protein. Chlordecone inhibited Ca²⁺‐ATPase in the absence of calmodulin with an IC ₅₀ of 10 μM, whereas chlordecone at 1.0 μM, 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.