Modulation of levels of free calcium within synaptosomes by organochlorine insecticides.
Effects of the organochlorine insecticides chlordecone, mirex, 1-(2-chlorophenyl)-1-(4-chlorophenyl)-2,2,2-trichloroethane and 1,1-bis(4-chlorophenyl)-2,2,2-trichloroethane on free intrasynaptosomal Ca2+ [( Ca++]i), synaptosomal 45Ca uptake and synaptosomal plasma and mitochondrial membrane potentials in vitro were studied. Chlordecone (10-50 microM) increased [Ca++]i from the resting level of 370 nM in a dose- and time-dependent manner to above 1.5 microM. This took place in the presence of 1 mM extrasynaptosomal Ca++ but not in nominally Ca++-free medium. Verapamil, a voltage sensitive Ca++ channel blocker, inhibited the initial increase of [Ca++]i caused by chlordecone, by 40%. Chlordecone also elevated [Ca++]i in synaptosomes in which mitochondrial Ca++ uptake had been abolished by valinomycin. Chlordecone depolarized partially the synaptosomal plasma membrane and, to a lesser extent, the potential of mitochondria within synaptosomes. However, chlordecone appeared to inhibit synaptosomal K+-stimulated and unstimulated 45Ca++ uptake by 20 to 30%. Inasmuch as chlordecone also stimulated release of 45Ca++ and the fluorescent dye fura-2 from preloaded synaptosomes, the apparent inhibition of uptake might be due to lysis of some synaptosomes by chlordecone. The effect of chlordecone on [Ca++]i decreased when the total amount of tissue in incubations was increased. [Ca++]i was only elevated marginally by mirex at the same concentration range. The results suggest that chlordecone increases free intrasynaptosomal Ca++ mainly by increasing influx of extrasynaptosomal Ca++. The principal mechanism appears to be a nonspecific leakage of Ca++ through the plasma membrane but some Ca++ may pass through voltage-sensitive Ca++ channels due to chlordecone-induced membrane depolarization.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D007631:Chlordecone / Q000494:pharmacology; D003634:DDT / Q000494:pharmacology; D007306:Insecticides / Q000494:pharmacology*; D007536:Isomerism; D008297:Male; D008433:Mathematics; D008917:Mirex / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D014634:Valinomycin / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D007306:Insecticides; D014634:Valinomycin; D003634:DDT; D014700:Verapamil; C016340:o,p'-DDT; D007631:Chlordecone; D002118:Calcium; D008917:Mirex