Interaction of chlordecone with biological membranes

Chlordecone (Kepone) is a close structural analog of mirex, but it differs considerably from mirex in toxic action. Chlordecone primarily produces neurotoxic symptoms such as tremors in humans and animals. As with other organochlorine pesticides, the mechanism of the toxic action of chlordecone is not completely understood. An attempt is made in this paper to review the effects of chlordecone on the membrane-bound adenosinetriphosphatases (ATPases) and related phenomena. Chlordecone is shown to be a potent inhibitor of ATPases in different tissue preparations of several species. The order of sensitivity of the ATPases tested to chlordecone was: oligomycin-sensitive (mitochondrial) Mg2+-ATPase greater than Na+,K+-ATPase greater than Ca2+-ATPase greater than oligomycin-insensitive Mg2+-ATPase. Compared to other tissues tested, brain Na+K+-ATPase and heart mitochondrial Mg2+-ATPase were more sensitive to chlordecone. Oligomycin-insensitive Mg2+-ATPase was the least affected enzyme. Membrane-bound Na+, K+-ATPase has been associated with catecholamine uptake processes, and inhibitors of this enzyme, such as ouabain, have been found to decrease catecholamine uptake. Chlordecone decreased the uptake of catecholamines by rat heart membranes in a dose-dependent manner. Various cellular processes such as catecholamine uptake are dependent for energy on ATP, and most of this ATP is produced in the mitochondria through oxidative phosphorylation. Oligomycin-sensitive Mg2+-ATPase is involved in this coupling process. Chlordecone inhibition of this enzyme may result in depletion of mitochondrial ATP. This chain of events suggest that chlordecone interacts with membrane ATPases and thus may impair various energy-dependent cellular processes.