Effects of ciguatoxin on current and voltage clamped frog myelinated nerve fibre.

The effects of 0.25 X 10(-9) and 1.25 X 10(-9) g/ml of purified ciguatoxin (CgTX) upon the node of Ranvier of frog isolated nerve fibres were investigated under current and voltage clamp conditions. When added to the external solution, CgTX induced spontaneous action potentials at a frequency of about 100 Hz, which were reversible upon removal of the toxin. Under voltage clamp conditions, CgTX modified neither linear leakage and capacity currents nor K current, but reversibly induced a maintained (late) inward current (IL) during long lasting depolarizations. IL, as well as the peak Na current, was suppressed by tetrodotoxin (300 nM). The steady-state inactivation curve of the Na current showed that a fraction of the current (corresponding to IL) did not inactivate. IL activated and reversed at voltages about 30 mV more negative than the peak Na current (recorded under control conditions or in the presence of CgTX). During a given depolarizing pulse, the amplitude of IL depended on the holding potential. IL was about three times greater when the holding potential was -70 mV rather than -120 mV. We conclude that CgTX specifically interacts with and modifies Na channels. We also conclude that the effects of CgTX depend on membrane potential.