Exposure to lindane and two other hexachlorocyclohexane isomers increases free intracellular calcium levels in neurohybridoma cells.
NCB-20 neurohybridoma cells were exposed to isomers of hexachlorocyclohexane (HCH) for periods of time ranging from 5-45 min, and intracellular free calcium [Ca++]i levels were determined using the INDO1/AM method. Exposure to lindane (gamma HCH) produced a dose-dependent increase in [Ca++]i, significant increases being observed with exposures from 10-400 microM. During exposure, [Ca++]i increased to a peak and then declined over the next 45 min. After 45 min levels were still elevated above control levels. This action of the gamma isomer of HCH was shared by the alpha and beta isomers. The potencies of the isomers were alpha (0.5), beta (0.75) and gamma (1.0). The effects of HCH isomers on [Ca++]i in neurohybridoma cells are similar to those reported for the isomers using rat brain synaptosomes. The ability of lindane to increase [Ca++]i may explain the previously reported ability of lindane to increase spontaneous and evoked (under low quantal release conditions) release of transmitter from frog neuromuscular junction. The relevance of this effect to mammalian CNS hyperexcitability, however, remains unsettled. These effects occur at concentrations of lindane higher than those effective in antagonizing GABA-mediated inhibition, and they lack the specificity shown by the isomers under other circumstances.
Joy
R M
RM
Department of Pharmacology and Toxicology, School of Veterinary Medicine, University of California Davis 95616.
Burns
V W
VW
D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D001556:Hexachlorocyclohexane / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism*
D001556:Hexachlorocyclohexane; D002118:Calcium