PHARMACOLOGY OF THE NICOTINIC ACETYLCHOLINE-RECEPTOR FROM FETAL-RAT MUSCLE EXPRESSED IN XENOPUS OOCYTES

The fetal rat muscle nicotinic acetylcholine receptor was expressed in Xenopus oocytes. Using the voltage-clamp technique, the response to a range of agonists was measured, listed in order of (decreasing) activ ity efficacy: anatoxin greater than or equal to epibatidine > acetylch oline > DMPP (1,1-dimethyl-4-phenylpiperazinium) much greater than cyt isine > pyrantel > nicotine > coniine > tubocurare > lobeline. The ago nist responses were compared with the steric and electrostatic propert ies of the molecules, using molecular modelling. Single-channel curren ts were measured in outside-out patches for acetylcholine, nicotine, c ytisine, anatoxin and epibatidine. The conductance of the single chann els was independent of the type of agonist. The mean open times were c haracteristic of the agonist applied. Tubocurare, better known for its antagonist properties, was also a partial agonist. Single-channel cur rents were also observed for tubocurare, and for methyllycaconitine in patches with a very high density of the muscle nicotinic acetylcholin e receptor, and these were blocked by alpha-bungarotoxin. The agonist properties of physostigmine, galanthamine and their methyl derivatives were also investigated. The conductance of the channels observed in o utside-out patches was similar to that obtained for the classical agon ists. The single-channel currents observed for physostigmine, galantha mine and their methyl derivatives were blocked by alpha-bungarotoxin, methyllycaconitine and mecamylamine, in contrast to previously reporte d studies on neuronal and adult muscle nicotinic acetylcholine recepto rs.