NON-GABA(A)-MEDIATED EFFECTS OF LINDANE ON NEURITE DEVELOPMENT AND INTRACELLULAR FREE CALCIUM-ION CONCENTRATION IN CULTURED RAT HIPPOCAMPAL-NEURONS

Changes in transmembrane Ca2+ fluxes and intracellular free Ca2+ ion c oncentrations ([Ca2+](in)) regulate many aspects of neurite developmen t in cultured neurons. Lindane has been shown to increase [Ca2+](in) i n several cell types. It was therefore hypothesized that lindane expos ure would increase [Ca2+](in) and thereby alter neurite development in cultured rat hippocampal neurons. The study reported here showed that lindane (50-100 mu M) increased [Ca2+](in) during short-term exposure (up to 4 hr); in contrast, with long-term exposure (24-48 hr) lindane (1-50 mu M) decreased [Ca2+](in) significantly below control levels. Lindane decreased neurite initiation at high concentrations (25 mu M o r above). Lindane increased dendrite number at low concentrations (0.5 -1 mu M), but decreased dendrite number at high concentrations (50 mu M or above). Lindane decreased axon and dendrite elongation and branch ing at 50 mu M. Loading neurons with 1 mu M -bis-(o-aminophenoxy)-etha ne-N,N,N',N'-tetraacetic acid (BAPTA), a calcium chelator that partial ly 'clamps' [Ca2+](in), eliminated the effects of 50 mu M lindane on [ Ca2+](in) in short-term exposures. BAPTA did not significantly reverse the inhibition of neurite initiation or axonal elongation caused by 5 0 mu M lindane. However, BAPTA partially reversed the inhibition of de ndrite elongation and completely reversed the inhibition of axon and d endrite branching caused by 50 mu M lindane. Therefore, some, but not all, of lindane's effects on neurite development may be due to changes in [Ca2+](in). Picrotoxin, a gamma-aminobutyric acid A (GABA(A))-asso ciated chloride channel antagonist, had no effect on [Ca2+](in) or any parameters of neurite growth, suggesting that the effects of lindane on neurite development and [Ca2+](in) were not mediated through action s on GABA(A)-associated chloride channels.