Alteration of oxytocin-induced calcium oscillations in Clone 9 cells by toxin exposure

A communication-competent rat liver cell line (Clone 9) was examined as a model system to investigate the action of toxins on [Ca²⁺](i) induced by extracellular signals. Clone 9 cells exhibit an initial [Ca²⁺](i) spike followed by Ca²⁺ oscillations for at least 30 min after exposure to oxytocin (10 to 1000 nM). Oscillations of mitochondrial membrane potential were also detected using the potentiometric fluorescent probe rhodamine 123. Fast Fourier Transform showed that complex patterns of oscillations in Clone 9 cells exhibit both amplitude- and frequency-encoded signals. The initial Ca²⁺ peak and oscillations were not altered by ryanodine pretreatment but were suppressed by nifedipine and blocked by thapsigargin. Brief exposure of cells to the food-borne toxins patulin or gossypol or the environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin at doses which have no effect on cell viability within the duration of experiments was used to monitor any changes in Ca²⁺ oscillations. Toxin treatment either blocked or changed the amplitude and/or frequency of Ca²⁺ oscillations depending upon the toxin-specific mechanisms of cellular injury. These studies indicate that toxic agents may alter amplitude- and frequency-encoded information derived from cell signaling events which could result in altered cellular homeostasis at nonlethal doses of toxin.