Analysis of atropine action at the frog neutromuscular junction.

Abstract

Atropine action on the end-plate currents (e.p.c.s) was analyzed at the macroscopic and elementary levels. The shortening effect of atropine on the e.p.c. and m.e.p.c. [miniture end-plate current] level can be fully explained by a reduction of the life time of the elementary current: this effect is markedly increased at more hyperpolarized membrane potentials and at higher concentrations of atropine. Atropine appears to bind to the open acetylcholine-receptor complex, leading to a state with a null conductance. According to this model, the forward rate constant of atropine binding could be calculated and was of the order of 107 M-1 s-1 at -90 mV and 20-22.degree. C. Although the conductance at the peak of the e.p.c. is reduced by atropine and becomes voltage sensitive, the elementary conductance is affected neither by voltage nor by atropine. The exclusive binding of atropine to the activated ACh-receptor complex, as proposed above, does not appear to explain this phenomenon. Another binding occurring before the channel is open with a dissociation constant of 60 .mu.M could account for this effect.