Activation of muscle nicotinic acetylcholine receptor channels by nicotinic and muscarinic agonists

1 The dose-response parameters of recombinant mouse adult neuromuscular ace tylcholine receptor channels (nAChR) activated by carbamylcholine, nicotine , muscarine and oxotremorine were measured. Rate constants for agonist asso ciation and dissociation, and channel opening and closing, were estimated f rom single-channel kinetic analysis. 2 The dissociation equilibrium constants were (mM): ACh (0.16)<oxotremorine M (0.6)<carbamylcholine (0.8) <nicotine (2.6). 3 The gating equilibrium constants (opening/closing) were: ACh (45)> carbam ylcholine (5.1)> oxotremorine M (0.6)>nicotine (0.5)>muscarine (0.15). 4 Rat neuronal alpha(4)beta(2) nAChR can be activated by all of the agonist s. However, detailed kinetic analysis was impossible because the recordings lacked clusters representing the activity of a single receptor complex. Th us, the number of channels in the patch was unknown and the activation rate constants could not be determined. 5 Considering both receptor affinity and agonist efficacy, muscarine and ox otremorine are significant agonists of muscle-type nAChR. The results are d iscussed in terms of structure-function relationships at the nAChR transmit ter binding site.