Desensitization is a property of the cholinergic binding region of the nicotinic acetylcholine receptor, not of the receptor-integral ion channel

Abstract

The reversible acctylchollne esternse inhibitor (-}.physostiilmine (¢serine) is th© prolotypc of a new class of nie~tinlc ucetylcholinc receptor (nAChR) activating liga,ds: it induces cation fluxes into nAChR.rich membrane vesicl~s from 7~r#eda marmoeata cle~:tric tissue even under condl. lions of antalionist blocked :tcctylcholin~ binding sil~s (Okonjo, Kuhlm~mn. Maelicke. Neuron, in press). This su~tlest's that escrine exerts it~ than. nel.activating proi'~rty via binding sites at the nAChR separate from those of tile natural transmitter. We now report thllt eserine e'-m activate the channel wen when the receptor has t~en preincub~ttcd (des©nsitiz©d) with elevated concentrations of acetylcholi~e, Titus the confornudional state Of the receptor corresponding to de~nsitixation is confined to the transmitter bindinB rclli0n, leaving the ch=tr'4nel fully activatable ,-albeit only from other than the tr~msmitter bindin~ site(s)