Conductances of single ion channels opened by nicotinic agonists are indistinguishable

Abstract

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^1–3. On the basis of noise analysis it has been reported that certain agonists open ion channels of lower conductance than usual^4–8, though many potent agonists give similar conductances^9–13, and hence that differences in the conductance of ion channels opened by different agonists may contribute to differences in efficacy¹⁴. Here we have reinvestigated this question by recording single ion channel currents¹⁵ 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^4,5. 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 conductances evoked by various agonists but presumably on the position of the open–shut equilibrium of the agonist–channel complexes¹⁶.