The depression in action potential induced by procaine can be arrested or even reversed by acetylcholine in the previously eserinized frog sciatic single fiber preparation. The extent and time course of the reversal are related to the relative concentrations of both procaine and acetylcholine and to the duration of the previous procaine exposure. Resting membrane potential is not affected. Repeated exposures to procaine are characterized by increasingly rapid onset of block, reduced susceptibility to actylcholine competition, and failure of complete recovery after removal of procaine. The time parameters of recovery from procaine depression are independent of the previously applied concentrations of either acetylcholine or procaine. Since acetylcholine has been shown not to cross the nerve membrane, the results are interpreted as indicating that the receptor involved in the competition exists on the external surface of the membrane.
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