Modification of sodium channel kinetics by the insecticide tetramethrin in crayfish giant axons.

The effects of the pyrethroid insecticide tetramethrin on voltage-dependent sodium channels were studied with internally perfused crayfish giant axons. At low concentrations in the order of 10-8-10-9M, tetramethrin caused an increase in depolarizing after-potential which in turn triggered repetitive after-discharges. Under Voltage clamp conditions, the sodium current was markedly prolonged during a step depolarization, and a large and prolonged sodium tail current appeared upon step repolarization. A population of sodium channels having activation and inactivation kinetics identical to those in control axons was observed in the tetramethrin-poisoned axons, indicating that only a fraction of the channels was modified. The modified channels exhibited remarkably slow kinetics, activating with a time course of 100 msec to 2 sec and inactivating with a time course of 1-5 sec depending on the membrane potential. The voltage dependence of the modified channels was shifted in the direction of hyperpolarization by about 10-20 mV with respect to normal sodium channels. The large inward sodium tail current associated with step repolarization of the membrane decayed with a time course of 20-600 msec. A kinetic hypothesis describing the behavior of sodium channels in a tetramethrin-poisoned axon is presented and discussed in relation of the behavior of the sodium channels modified by other toxins.