ALTERATION OF OXYTOCIN-INDUCED CALCIUM OSCILLATIONS IN CLONE-9 CELLS BY TOXIN EXPOSURE

A communication-competent rat liver cell line (Clone 9) was examined a s a model system to investigate the action of toxins on [Ca2+](i) indu ced by extracellular signals. Clone 9 cells exhibit an initial [Ca2+]( i) spike followed by Ca2+ oscillations for at least 30 min after expos ure to oxytocin (10 to 1000 nM). Oscillations of mitochondrial membran e potential were also detected using the potentiometric fluorescent pr obe rhodamine 123. Fast Fourier Transform showed that complex patterns of oscillations in Clone 9 cells exhibit both amplitude- and frequenc y-encoded signals. The initial Ca2+ peak and oscillations were not alt ered by ryanodine pretreatment but were suppressed by nifedipine and b locked by thapsigargin. Brief exposure of cells to the food-borne toxi ns patulin or gossypol or the environmental toxicant 2,3,7,8-tetrachlo ro-dibenzo-p-dioxin at doses which have no effect on cell viability wi thin the duration of experiments was used to monitor any changes in Ca 2+ oscillations. Toxin treatment either blocked or changed the amplitu de and/or frequency of Ca2+ oscillations depending upon the toxin-spec ific mechanisms of cellular injury. These studies indicate that toxic agents mag. alter amplitude- and frequency-encoded information derived from cell signaling events which could result in altered cellular hom eostasis at nonlethal doses of toxin. (C) 1996 Society of Toxicology