Non-GABA(A)-mediated effects of lindane on neurite development and intracellular free calcium ion concentration in cultured rat hippocampal neurons.
Changes in transmembrane Ca(2+) fluxes and intracellular free Ca(2+) ion concentrations ([Ca(2+)](in)) regulate many aspects of neurite development in cultured neurons. Lindane has been shown to increase [Ca(2+)](in) in several cell types. It was therefore hypothesized that lindane exposure would increase [Ca(2+)](in) and thereby alter neurite development in cultured rat hippocampal neurons. The study reported here showed that lindane (50-100 muM) increased [Ca(2+)](in) during short-term exposure (up to 4 hr); in contrast, with long-term exposure (24-48 hr) lindane (1-50 mum) decreased [Ca(2+)](in) significantly below control levels. Lindane decreased neurite initiation at high concentrations (25 mum or above). Lindane increased dendrite number at low concentrations (0.5-1 muM), but decreased dendrite number at high concentrations (50 mum or above). Lindane decreased axon and dendrite elongation and branching at 50 mum. Loading neurons with 1 mum 1,2-bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA), a calcium chelator that partially 'clamps' [Ca(2+)](in), eliminated the effects of 50 mum lindane on [Ca(2+)](in) in short-term exposures. BAPTA did not significantly reverse the inhibition of neurite initiation or axonal elongation caused by 50 mum lindane. However, BAPTA partially reversed the inhibition of dendrite elongation and completely reversed the inhibition of axon and dendrite branching caused by 50 mum lindane. Therefore, some, but not all, of lindane's effects on neurite development may be due to changes in [Ca(2+)](in). Picrotoxin, a gamma-aminobutyric acid A (GABA(A))-associated chloride channel antagonist, had no effect on [Ca(2+)](in) or any parameters of neurite growth, suggesting that the effects of lindane on neurite development and [Ca(2+)](in) were not mediated through actions on GABA(A)-associated chloride channels.
Ferguson
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Biology Department, University of Colorado at Denver, PO Box 173364, Denver, CO 80217-3364, USA.
Audesirk
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