Subunit-Specific Action of an Anticonvulsant Thiobutyrolactone on Recombinant Glycine Receptors Involves a Residue in the M2 Membrane-Spanning Region

The anticonvulsant a-ethyl, a-methyl-g-thiobutyrolactone (aEMTBL) potentiates the response to a submaximal concentration of gly-cine produced by receptors composed of human glycine a1-subunits but reduces the response of receptors composed of rat glycine a3-subunits. Both the potentiating and blocking actions of aEMTBL are reduced by higher concentrations of glycine. The subunit specificity of aEMTBL block is conferred by a residue in the second membrane-spanning region (M2), which is alanine in the a3-subunit (A254) and glycine in the a1-subunit. The mutation A254G in the a3-subunit removes blocking by aEMTBL and re-veals potentiation. Picrotin, a picrotoxinin analog, blocks re-sponses of receptors composed of either a1 or a3-subunits. Blocking of a3 receptors by picrotin is reduced in the presence of aEMTBL, indicating that the mechanisms interact at some point