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

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 GluCl beta responds to glutamate as a homomeric channel while the GluCl alpha subunit is insensitive. A chimera between GluCl alpha and GluCl beta was used to suggest that major determinants for glutamate binding are present on the GluCl alpha N terminus, Amino acid substitutions in the presumed pore of GluCl alpha conferred direct glutamate gating indicating that GluCl alpha is deficient in coupling of ligand binding to channel gating. Heteromeric channels of GluCl alpha+beta 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.