Effect of substituted benzyl chrysanthemates on sodium and potassium currents in the crayfish giant axon

Abstract

The effects of substituted benzyl (1 R)- trans-chrysanthemates on sodium and potassium currents were studied in voltage-clamped crayfish giant axons. The o-SO 2Me derivative decelerated the rate of the falling phase of the action potential (type A effect), and the p-SO 2Me derivative elevated the depolarizing afterpotential (type B effect). The o-SO 2Me derivative inhibited the inactivation of sodium channels. The time constant of the inactivation of sodium channels affected by the ortho derivative was 5–10 times that of the unaffected channels. The fraction of channels affected compared to the total sodium channels progressively increased during the administration of the drug. Voltage-sensitive potassium channels also were blocked progressively. The p-SO 2Me derivative markedly slowed down the inactivation and induced a large residual current during depolarization. The time constant of the inactivation of sodium channels affected by this drug was 50–100 times that in control axons. Upon repolarization, a large tail current was observed, indicating that the restoration of gating groups responsible for the activation to the nonconducting position on repolarization also was suppressed in some affected channels. The m-CN derivative, which had a mixed effect of both types A and B on the action potential, caused both moderate slowing of the inactivation of some sodium channels and induction of the residual current. During the administration of this drug, a small tail current was observed upon step repolarization. We concluded that the type A effect on action potential is due to moderate slowing of the inactivation of the sodium channels and blocking of some fraction of voltage-sensitive potassium channels, and that the type B effect is due to extremely slow inactivation of sodium channels and the slowing of closing kinetics of the activation gate upon repolarization affected by drugs of this group.