A Single Site on the ε Subunit Is Responsible for the Change in ACh Receptor Channel Conductance during Skeletal Muscle Development

Abstract Four critically positioned amino acids on each of the αβ, δ and γ sunits of the Torpedo nicotinic acetylcholine receptor are determinants of channel conductance. Our results show that the γ and ϵ subunits of Xenopus muscle receptors are identical at all four positions, despite the fact that α 2 βδϵ receptors have a 50% greater conductance than α 2 βδγ receptors. Instead, the functional difference is conferred by a single charged residue that lies extracellular to all four positions, corresponding to a location in the Torpedo receptor previously shown to have no influence on conductance. Substitution of a positively charged lysine residue in γ by the neutral methionine in ϵ at this extracellular position is responsible for the increased conductance during maturation of the amphibian neuromuscular junction.