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Alteration of calcium influx in rat cortical synaptosomes by soman
1Pharmacology and Therapeutics, Biomedical Defence Section, Defence Research Establishment Suffield, Hat, Alberta, Canada.
Abstract:
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.
Insights
Organophosphate poisoning, like soman, disrupts calcium (Ca2+) homeostasis in the brain, leading to neuronal damage. This study shows elevated Ca2+ influx after soman exposure contributes to neurotoxicity.
Area of Science:
- Neuroscience
- Toxicology
- Biochemistry
Background:
- Organophosphate (OP) compounds, such as soman, are known neurotoxins.
- OP poisoning can lead to neuronal death in various brain regions.
- Disruption of calcium (Ca2+) homeostasis is a potential mechanism for OP-induced neurotoxicity.
Purpose of the Study:
- To investigate if impaired Ca2+ homeostasis is sufficient to cause OP-induced neurotoxicity.
- To determine the effect of soman exposure on neuronal Ca2+ influx.
- To assess the duration of altered Ca2+ homeostasis following soman intoxication.
Main Methods:
- Assessment of K(+)-stimulated synaptosomal Ca2+ influx in rodents post-soman exposure.
- Measurement of resting Ca2+ accumulation in synaptosomes.
- Comparison of Ca2+ influx at different time points and soman doses (1 or 4 LD50).
Main Results:
- K(+)-stimulated Ca2+ influx was significantly elevated 24 hours after soman challenge.
- Elevated neuronal Ca2+ influx persisted for 2 days (1 LD50) and at least 7 days (4 LD50).
- No significant effect on resting Ca2+ accumulation was observed, indicating specificity for depolarization-induced influx.
Conclusions:
- Increased intracellular Ca2+ levels resulting from soman exposure may contribute to neuronal degeneration.
- Disruption of Ca2+ homeostasis is a significant factor in soman-induced neurotoxicity.
- These findings highlight the role of calcium dysregulation in OP poisoning pathology.