Gambierol blocks a K(+) current fraction and affects action potential duration and the firing rate in rat fetal chromaffin cells
Résumé
The dinoflagellate genus Gambierdiscus, particularly Gambierdiscus toxicus is known to produce numerous ladder polycyclic ether compounds, including gambierol, characterized by a transfused octacyclic polyether core, as well as the identified ciguatoxins responsible for ciguatera poisoning. Gambierol inhibits voltage-gated K$^+$ (K$_V$) channels in various mammalian excitable and nonexcitable cells, and motor nerve terminals of the neuromuscular junction. In the present study, we investigated the action of gambierol on outward K$^+$ currents of cultured rat fetal adrenal medulla chromaffin cells using the whole-cell configuration voltage-clamp method. The pharmacological dissection of the outward K$^+$current, using selective K$^+$ channel inhibitors, revealed that gambierol reduced just a small fraction of the total outward current without affecting calcium-activated K$^+$ currents that were sensitive to apamin and iberiotoxin, and ATP-sensitive K$^+$ currents sensitive to glibenclamide. Cultured fetal chromaffin cells were excitable and generated either evoked (upon direct electric stimulation) or spontaneous action potentials. These action potentials were sensitive to tetrodotoxin that blocks voltage-gated Na$^+$(Na$_V$) channels. Gambierol neither affected the rising phase nor the overshoot of action potentials but significantly prolonged their repolarizing phase and increased the firing rate of action potentials during sustained current depolarization, as determined using current-clamp recordings. Our results highlight the effects of gambierol on K$_V$ channels and on the electrical properties of rat fetal chromaffin cells. It is likely that gambierol may cross the placental barrier as ciguatoxins do. Further studies are needed to determine whether such actions may have deleterious effects on fetuses.
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