Lindane-induced modulation of calcium levels within synaptosomes.
The effect of three isomers of hexachlorocyclohexane upon synaptosomal levels of free calcium [Ca2+]i have been studied. The convulsant gamma isomer (lindane) and also the beta isomer, both caused, dose increases in [Ca2+]i while the alpha isomer was inactive. In the case of lindane, this [Ca2+]i response was greatly attenuated in the absence of added calcium to the incubation medium. All isomers caused increased permeability of the synaptosomal limiting membrane but at a lower concentration only lindane was effective. This increased permeability was apparent even in calcium-free buffer. The depolarization-stimulated entry of radioactive calcium, 45Ca2+, into synaptosomes was reduced in the presence of a relatively high concentration of all hexachlorocyclohexane isomers, this effect being most pronounced for lindane. This was attributed to damage to a high proportion of synaptosomes by the high concentrations of isomers used, preventing evaluation of calcium uptake by surviving synaptosomes. Damage to the plasma membrane, and consequent elevation of [Ca2+]i may be an underlying factor in, but cannot totally account for, the hyperactive or convulsive states found after exposure to lindane.
Bondy
S C
SC
Department of Community and Environmental Medicine, University of California, Irvine 92717.
Halsall
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L
D000818:Animals; D002118:Calcium / Q000493:pharmacokinetics*; D005456:Fluorescent Dyes; D001556:Hexachlorocyclohexane / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013237:Stereoisomerism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D005456:Fluorescent Dyes; D001556:Hexachlorocyclohexane; D002118:Calcium