Mode of Action of Trichloroethylene on Squid Axon Membranes

The mode of action of trichloroethylene on electrical properties of squid giant axons has been studied by means of voltage clamp techniques. Trichloroethylene decreased the resting membrane potential in a manner dependent upon the concentration, the depolarization by 50% saturated trichloroethylene attaining 28.4 and 32.7% of the initial value at 20 and 10 degrees C, respectively. Leakage conductance was decreased to 34.6% of the control by 30% saturated trichloroethylene at 10-12 degrees C. It appears that the trichloroethylene-induced depolarization is at least in part due to a decrease in resting potassium permeability. Both peak transient and steady-state conductance increases were suppressec by trichloroethylene, and the curve relating the steady-state conductance to the membrane potential was shifted in the depolarizing direction while the peak transient conductance curve was not appreciably shifted. The reversal potential for the peak transient current was greatly shifted by trichloroethylene in the direction of hyperpolarization in a manner dependent on the concentration, the maximum shift amounting to 25 mV at 10 degrees C. This effect was less pronounced at 20 degrees C. The shift in the reversal potential is mostly due to a decrease in selectivity of the peak transient channel and partly due to an accumulation of sodium ions inside. Analyes of dose-response relation in suppressing peak transient and steady-state conductances show that trichloroethylene interacts with receptor on a one-to-one stoichiometric basis. Steady-state sodium inactivation curve was shifted by trichloroethylene in the direction of hyperpolarization. All of these effects were partially reversed after washing the axon with anesthetic-free media. The accumulation of sodium ions inside would be much more pronounced in small nerve fibers in the brain than in giant axon and, together with the observed decrease in the selectivity of peak transient channels, would play a significant role in general anesthesia.