Activation of ion channels in the frog endplate by several analogues of acetylcholine.
1. Single-ion-channel recording has been used to estimate the equilibrium concentration-response relationship for several acetylcholine analogues. The response, corrected for desensitization, was taken as the probability of a channel being open during clusters of openings that were separated by desensitized periods. 2. All agonists were able to block the channels which they themselves opened. Carbachol, suberyldicholine and the sulphonium analogue of acetylcholine were all found to be efficacious agonists in the sense that the results indicate that all of them, in sufficiently high concentration, would be able to open 90% or more of channels if it were not for channel block. 3. In the case of suberyldicholine the results are much as predicted by the interpretation of the fine structure of channel openings at low agonist concentrations. 4. The maximum probability of opening that could be obtained with decamethonium and with phenyltrimethylammonium was low (below 4%), and it was not possible to distinguish whether this was wholly a result of the powerful (relative to activation potency) channel-blocking action of these agonists, or whether it was to some extent attributable to their being genuine partial agonists. 5. The results suggest that, for a range of agonists, differences in equilibrium potency are usually more strongly influenced by affinity for binding to the resting state of the receptor than by ability to activate the receptor once bound, though in the case of suxamethonium (relative to acetylcholine) the contributions of each factor are similar.
Marshall
C G
CG
Department of Pharmacology, University College London.
Ogden
D
D
Colquhoun
D
D
D000109:Acetylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002794:Choline / Q000031:analogs & derivatives / Q000494:pharmacology; D003650:Decamethonium Compounds / Q000494:pharmacology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D009045:Motor Endplate / Q000187:drug effects* / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D011896:Rana temporaria; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D003650:Decamethonium Compounds; D007473:Ion Channels; D000644:Quaternary Ammonium Compounds; D013757:Tetraethylammonium Compounds; C009335:subecholine; D019789:Tetraethylammonium; D002217:Carbachol; C033019:decamethonium; C027917:tetramethylammonium; D002794:Choline; D000109:Acetylcholine