MODE OF ACTION OF TRICHLOROETHYLENE ON SQUID AXON-MEMBRANES

  • 1 January 1976
    • journal article
    • research article
    • Vol. 199  (1) , 179-188
Abstract
The mode of action of trichloroethylene [TCE] on electrical properties of squid [Loligo pealei] giant axons was studied using voltage clamp techniques. TCE decreased the resting membrane potential in a manner dependent upon the concentration, the depolarization by 50% saturated TCE attaining 28.4 and 32.7% of the initial value at 20 and 10.degree. C, respectively. Leakage conductance was decreased to 34.6% of the control by 30% saturated TCE at 10-12.degree. C. The TCE-induced depolarization was at least partly due to a decrease in resting K+ permeability. Both peak transient and steady-state conductance increases were suppressed by TCE, 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 TCE in the direction of hyperpolarization in a manner dependent on the concentration, the maximum shift amounting to 25 mV at 10.degree. C. This effect was less pronounced at 20.degree. C. The shift in the reversal potential was mostly due to a decrease in selectivity of the peak transient channel and partly due to an accumulation of Na+ inside. Analyses of dose-response relations in suppressing peak transient and steady-state conductances showed that TCE interacts with receptor on a one-to-one stoichiometric basis. Steady-state Na+ inactivation curve was shifted by TCE in the direction of hyperpolarization. All these effects were partially reversed after washing the axon with anesthetic-free media. The more pronounced accumulation of Na+ inside small nerve fibers in the brain than in giant axons together with the observed decrease in the selectivity of peak transient channels, probably plays a significant role in general anesthesia.