Alteration of calcium influx in rat cortical synaptosomes by soman.
Poisoning by soman causes changes in brain activity leading to neuronal death in several brain areas. We investigated whether disruption of normal Ca2+ homeostasis was sufficient to account for at least some of the OP-induced neurotoxicity. Beginning 24 h after a challenge with soman (1 or 4 LD50) K(+)-stimulated synaptosomal Ca2+ influx was significantly elevated above that in control animals. Neuronal Ca2+ influx remained elevated for two days after 1 LD50 of soman and at least 7 days after 4 LD50. The effect was specific for depolarization induced influx as there was no effect on resting (5 mM K+) Ca2+ accumulation. These results suggest that increased intracellular Ca2+ may contribute to the neuronal degeneration and neurotoxicity observed after poisoning with soman.
Hamilton
M G
MG
Pharmacology and Therapeutics, Biomedical Defence Section, Defence Research Establishment Suffield, Hat, Alberta, Canada.
Posavad
C
C
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002801:Cholinesterase Reactivators / Q000494:pharmacology; D066298:In Vitro Techniques; D007928:Lethal Dose 50; D008297:Male; D010091:Oximes; D011189:Potassium Chloride / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012999:Soman / Q000494:pharmacology* / Q000633:toxicity; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D002801:Cholinesterase Reactivators; D010091:Oximes; D011726:Pyridinium Compounds; D011189:Potassium Chloride; D012999:Soman; C022870:asoxime chloride; D002118:Calcium