Lindane-induced modulation of calcium levels within synaptosomes

Area of Science:

• Neuroscience
• Toxicology
• Cell Biology

Background:

• Hexachlorocyclohexane (HCH) isomers are organochlorine pesticides with varying toxicological profiles.
• Synaptosomes, isolated nerve terminals, are crucial for studying neurotransmission and calcium homeostasis.
• Understanding the impact of HCH isomers on neuronal calcium is vital for assessing neurotoxicity.

Purpose of the Study:

• To investigate the effects of three HCH isomers (alpha, beta, and gamma/lindane) on intracellular free calcium ([Ca2+]i) levels in synaptosomes.
• To determine how HCH isomers influence synaptosomal membrane permeability and calcium influx.
• To elucidate the mechanisms underlying lindane-induced neurotoxicity.

Main Methods:

• Measurement of intracellular free calcium ([Ca2+]i) in isolated synaptosomes.
• Assessment of synaptosomal membrane permeability using various techniques.
• Studies conducted in both calcium-containing and calcium-free incubation media.
• Evaluation of depolarization-stimulated calcium-45 (45Ca2+) uptake into synaptosomes.

Main Results:

• The convulsant gamma isomer (lindane) and beta isomer dose-dependently increased [Ca2+]i, while the alpha isomer was inactive.
• Lindane's effect on [Ca2+]i was significantly reduced in calcium-free media.
• All HCH isomers increased synaptosomal membrane permeability; lindane was most potent at lower concentrations.
• High concentrations of all isomers reduced depolarization-stimulated 45Ca2+ uptake, likely due to synaptosome damage.

Conclusions:

• Lindane and beta-HCH disrupt calcium homeostasis in synaptosomes, contributing to neurotoxic effects.
• Increased membrane permeability and altered calcium levels are key mechanisms of HCH neurotoxicity.
• While plasma membrane damage and calcium elevation are implicated, they do not fully explain lindane's convulsant action.