THE LOCATION OF THE GATE IN THE ACETYLCHOLINE-RECEPTOR CHANNEL

The cation-conducting channel of the nicotinic acetylcholine (ACh) rec eptor is lined by the first (M1) and second (M2) membrane-spanning seg ments of each of its five subunits. Six consecutive residues, alpha S2 39 to alpha T244, in the alpha subunit M1-M2 loop and at the intracell ular end of M2 were mutated to cysteine. The accessibility of the subs tituted cysteines were probed with small, cationic, sulfhydryl-specifi c reagents added extracellularly and intracellularly. In the closed st ate of the channel, there is a barrier to these reagents added from ei ther side between alpha G240 and alpha T244. ACh induces the removal o f this barrier, which acts as an activation gate. The residues alpha G 240, alpha E241, alpha K242, and alpha T244 line a narrow part of the channel, in which this gate is located.