An amino acid substitution in the pore region of a glutamate-gated chloride channel enables the coupling of ligand binding to channel gating

Abstract

Many of the subunits of ligand-gated ion channels respond poorly, if at all, when expressed as homomeric channels in Xenopus oocytes. This lack of a ligand response has been thought to result from poor surface expression, poor assembly, or lack of an agonist binding domain. The Caenorhabditis elegans glutamate-gated chloride channel subunit GluClβ responds to glutamate as a homomeric channel while the GluClα subunit is insensitive. A chimera between GluClα and GluClβ was used to suggest that major determinants for glutamate binding are present on the GluClα N terminus. Amino acid substitutions in the presumed pore of GluClα conferred direct glutamate gating indicating that GluClα is deficient in coupling of ligand binding to channel gating. Heteromeric channels of GluClα+β may differ from the prototypic muscle nicotinic acetylcholine receptor in that they have the potential to bind ligand to all of the subunits forming the channel.