A comparative study of the activation of the cholinergic receptor by various agonists

Abstract

At the frog neuromuscular junction, a dose--response curve for the activation of the nicotinic receptor by carbachol has been determined under conditions where desensitization could be estimated and corrected for. The value of the Hill coefficient was 2 and that of the dissociation constant for carbachol was 400 $\mu $M, the two binding sites of the receptor being assumed identical. The properties of six cholinergic agonists were then compared. The potencies and mean open times of these agonists are ranked in the same order, but the range of the potencies is much larger (1-200) than that of the mean open times (1-4). The differences in the properties of the different agonists could simply be due to differences in the rate of dissociation of the agonist, if it is assumed that one apparent opening of the channel is in fact a burst of several oscillations between the open and closed conformations, such that a burst is interrupted by the dissociation of one agonist molecule.