The mode of action of the nicotinic cholinergic receptor protein in the postsynaptic membrane

Abstract

The functional properties of the cholinergic (nicotinic) receptor protein were discussed. on the basis of in vitro studies of membrane fragments of Electrophorus and Torpedo electric tissues. The membrane fragments of both are excitable in vitro. In contrast with the membrane fragments of Electrophorus, however, those of Torpedo give dose-response curves of in vitro excitation that shift towards higher concentration of the agonists by one to two orders of magnitude compared with the actual binding curves of agonists to the receptor sites. Moreover, they exhibit the phenomenon of pharmacological desensitization in a completely cell-free system. It was suggested that the discrepancy between the dose-response and the binding curves is related to the desensitization. The mechanism and the molecular events of desensitization are discussed. Desensitization is a reflection of a conformational change of the receptor protein during the excitation caused by agonists. This conformational change causes desensitization in subsynaptic membranes, through amplification. The regulatory properties of the cholinergic receptor protein similar to those of allosteric enzymes were discussed