A study of curare action with an electrical micro-method

Abstract

A micromethod is described by which depolarizing and inhibiting drugs can be applied, ionophoretically, from a common 'point source' to sensitive regions of a motor end-plate. The effects of the drugs on the membrane potential of a single end-plate are recorded, in the frog's sartorius muscle. The antagonism between d-tubocurarine (DTC) and acetylcholine (or carbachol) is studied with this method. Close-range application of small quantities of the depolarizing agents (of the order of several times $10^{-11}$ coulombs, or $10^{-16}$ $\text{M})$ sets up transient potential changes of several millivolts amplitude. Application of a somewhat larger quantity of DTC (about $4\times 10^{-10}$ $\text{C)}$ produces a transient 50% inhibition of the acetylcholine (or carbachol) potential. Curare does not alter the resting potential, nor the resistance or capacity of the end-plate or muscle fibre, but specifically interferes with the chemo-receptor properties of the end-plate. The inhibitory effect of DTC is obtained only with external application, but not with intracellular application from the inside of the muscle fibre. The decay of the inhibitory action of DTC is slow compared with the subsidence of the depolarization produced by acetylcholine or carbachol. The reason for this difference in time course is examined; it is probably due to relatively slow dissociation of the curare-receptor complex. Procaine in close-range, short-time application is as potent an inhibitor of acetylcholine action as DTC. The procaine effect subsides, however, much more rapidly than the action of curare.