THE EFFECT OF GUANIDINE ON NEUROMUSCULAR TRANSMISSION

¹ Department of Pharmacology, University of Tokyo, Japan

The effect of guanidine on neuromuscular transmission was studied in the sciatic-sartorius preparation of the frog, using intracellular electrodes. The sensitivity of the ned-plate to ACh was measured by applying ACh electrophoretically. Guanidine was also applied in the same way.

Guanidine greatly increased the amplitude of e.p.p. of curarized muscle without changing the resting potential at the end-plate region. Guanidine exhibited no effect on the cholinesterase activity, and it did not change the sensitivity of the end-plate to ACh. It is concluded that the drug increases the amplitude of e.p.p. by increasing the quantity of ACh released from the nerve ending by a single nerve impulse.

Membrane potential was recorded from endplates of guanidine-treated nerve-muscle preparation showing spontaneous twitchings. The most striking event was the appearance of spontaneous e.p.p.'s of more than 5 mV size (‘giant potential’), some of which did not reach threshold the others elicited the conducted action potentials.

When neuromuscular transmission was blocked with deploarizing agents, guanidine incedased the amplitude of e.p.p. to the point of cliciting a propagated action potential and muscle contraction.

As a possible mechanism, the increased presynaptic excitability and enhancement of the presynaptic excitation process were discussed.