Role of a serine residue (S278) in the pore-facing region of the housefly l-glutamate-gated chloride channel in determining sensitivity to noncompetitive antagonists

γ-Hexachlorocyclohexane (γ-HCH), fipronil and picrotoxinin are noncompetitive antagonists (NCAs) of l-glutamate-gated chloride channels (GluCls), yet their potencies are weaker than those on γ-aminobutyric acid receptors (GABARs). The A302S mutation of Drosophila RDL (resistant to dieldrin) GABAR confers NCA resistance, and housefly GluCls (MdGluCls) possess S278 as the residue corresponding to the A302. Thus, the effects of S278A mutation on the NCA actions on MdGluCls were investigated. The S278A mutation resulted in enhanced blocking by NCAs of the MdGluCl response to 30 μM l-glutamate. However, such actions of γ-HCH and picrotoxinin, but not of fipronil, on the S278A mutant were reduced with 200 μM l-glutamate. Further increases in the l-glutamate concentration led to potentiation by NCAs of the mutant response to l-glutamate.