Pacific ciguatoxin‐1b effect over Na + and K + currents, inositol 1,4,5‐triphosphate content and intracellular Ca 2+ signals in cultured rat myotubes

The action of the main ciguatoxin involved in ciguatera fish poisoning in the Pacific region (P‐CTX‐1b) was studied in myotubes originated from rat skeletal muscle cells kept in primary culture. The effect of P‐CTX‐1b on sodium currents at short times of exposure (up to 1 min) showed a moderate increase in peak Na + current. During prolonged exposures, P‐CTX‐1b decreased the peak Na + current. This action was always accompanied by an increase of leakage currents, tail currents and outward Na + currents, resulting in an intracellular Na + accumulation. This effect is blocked by prior exposure to tetrodotoxin (TTX) and becomes evident only after washout of TTX. Low to moderate concentrations of P‐CTX‐1b (2–5 n M ) partially blocked potassium currents in a manner that was dependent on the membrane potential. P‐CTX‐1b (2–12 n M ) caused a small membrane depolarization (3–5 mV) and an increase in the frequency of spontaneous action potential discharges that reached in general low frequencies (0.1–0.5 Hz). P‐CTX‐1b (10 n M ) caused a transient increase of intracellular inositol 1,4,5‐trisphosphate (IP 3 ) mass levels, which was blocked by TTX. In the presence of P‐CTX‐1b (10 n M ) and in the absence of external Ca 2+ , the intracellular Ca 2+ levels show a transient increase in the cytoplasm as well as in the nuclei. The time course of this effect may reflect the action of IP 3 over internal stores activated by P‐CTX‐1b‐induced membrane depolarization.British Journal of Pharmacology (2002) 137 , 1055–1062. doi: 10.1038/sj.bjp.0704980