Interaction of DDT with sodium channels in squid giant axon membranes

The effects of DDT on the sodium channel gating mechanism were studied with internally perfused squid giant axons under voltage clamp conditions. In contrast to earlier studies, DDT has pronounced effects on the sodium conductance system of squid axons. Internal application of 1 × 10^?4M DDT had no effect on the activation time constant (τ_m) or on the peak current, but the falling phase of the sodium current and the tail current upon repolarization were slowed dramatically (τ_tail= 3–13 ms). The sodium inactivation process became second order after DDT treatment. The time constant of the fast phase (τ₁) was identical to τ_h recorded in the control axon, while the time constant of the slow phase (τ₂) was more than 10 times greater. The voltage dependence of τ₂ was different from τ_h, increasing with depolarization. The steady-state inactivation curve was shifted in the direction of hyperpolarization by 6–8 mV, but even after prolonged depolarizing pulses, the sodium conductance did not inactivate completely.These data are consistent with the hypothesis that a population of sodium channels modified by DDT activates normally but is then retained in a second open state which inactivates slowly.