Conductances of single ion channels opened by nicotinic agonists are indistinguishable

Hypotheses concerning the mechanism by which acetylcholine-like agonists cause ion channels to open often suppose that the receptor-ionophore complex can exist in either of two discrete conformations, open and shut. On the basis of noise analysis it has been reported that certain agonists open ion channels of lower conductance than usual, though many potent agonists give similar conductances, and hence that differences in the conductance of ion channels opened by different agonists may contribute to differences in efficacy. Here we have reinvestigated this question by recording single ion channel currents evoked by acetylcholine-like agonists on embryonic rat muscle in tissue culture and on adult frog muscle endplate. Ten different agonists (Fig. 1) were tested, including several that noise analysis has suggested have a low conductance. The single-channel conductance was found to be the same, within a few per cent, for all 10 agonists. It seems that noise analysis has given erroneously low conductances in some cases. Therefore efficacy differences do not depend on differences in single-channel conductance evoked by various agonists but presumably on the position of the open-shunt equilibrium of the agonist-channel complexes.