Carta V Pangerl M Baur R Puthenkalam R Ernst M Trauner D Sigel E 2014 γ-Aminobutyric acid type A receptors (GABAA receptors) are chloride ion channels composed of five subunits, mediating fast synaptic and tonic inhibition in the mammalian brain. These receptors show near five-fold symmetry that is most pronounced in the second trans-membrane domain M2 lining the Cl- ion channel. To take advantage of this inherent symmetry, we screened a variety of aromatic anions with matched symmetry and found an inhibitor, pentacyanocyclopentdienyl anion (PCCP-) that exhibited all characteristics of an open channel blocker. Inhibition was strongly dependent on the membrane potential. Through mutagenesis and covalent modification, we identified the region α1V256-α1T261 in the rat recombinant GABAA receptor to be important for PCCP- action. Introduction of positive charges into M2 increased the affinity for PCCP- while PCCP- prevented the access of a positively charged molecule into M2. Interestingly, other anion selective cys-loop receptors were also inhibited by PCCP-, among them the Drosophila RDL GABAA receptor carrying an insecticide resistance mutation, suggesting that PCCP- could serve as an insecticide. application/pdf https://sonar.ch/global/documents/138917 eng info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0106688 info:eu-repo/semantics/altIdentifier/pmid/25184303 info:eu-repo/semantics/openAccess PloS one. - 2014 Amino Acid Substitution Animals Drosophila Proteins Drosophila melanogaster GABA-A Receptor Antagonists Mutation, Missense Protein Structure, Secondary Protein Structure, Tertiary Rats Receptors, GABA-A A pentasymmetric open channel blocker for Cys-loop receptor channels. http://purl.org/coar/resource_type/c_6501