Mutations in the channel domain of a neuronal nicotinic receptor convert ion selectivity from cationic to anionic

Introduction by site-directed mutagenesis of three amino acids from the Mil segment of glycine or & GAMMA;-aminobutyric acid (GABA A ) receptors into the Mil segment of α7 nicotinic receptor was sufficient to convert a cation-selective channel into an an ion-selective channel gated by acetylcholine. A critical mutation was the insertion of an uncharged residue at the amino-terminal end of Mil, stressing the importance of protein geometrical constraints on ion selectivity.