TY - JOUR T1 - Desensitization of Homomeric α1 Glycine Receptor Increases with Receptor Density JF - Molecular Pharmacology JO - Mol Pharmacol SP - 817 LP - 827 DO - 10.1124/mol.62.4.817 VL - 62 IS - 4 AU - Pascal Legendre AU - Emilie Muller AU - Carmen Ionela Badiu AU - Jochen Meier AU - Christian Vannier AU - Antoine Triller Y1 - 2002/10/01 UR - http://molpharm.aspetjournals.org/content/62/4/817.abstract N2 - Variations in the number of receptors at glycinergic synapses are now established and are believed to contribute to inhibitory synaptic plasticity. However, the relation between glycine receptor (GlyR) kinetics and density is still unclear. We used outside-out patch-clamp recordings and fast-flow application techniques to resolve fast homomeric GlyRα1 kinetics and to determine how the functional properties of these receptors depend on their density and on the presence of the anchoring protein gephyrin. The expression of GlyRs in human embryonic kidney cells increased with time and was correlated with an increase in GlyR desensitization at 2 days after transfection. Cotransfection of homomeric GlyRα1 bearing the gephyrin-binding site with gephyrin also increased desensitization but at 1 day after transfection compared with transfections of homomeric GlyRα1 without gephyrin. This increase results from the occurrence of a fast desensitization component and short applications of a saturating concentration of glycine suffice to promote a rapidly entered desensitized closed state. The level of desensitization changed neither the EC50 value nor the Hill coefficient of the glycine dose-response curves because the amplitude of the current was measured at the peak of the responses. These results demonstrate that variations in GlyR density during cluster formation result from a change in GlyR efficiency due to modifications in their desensitization properties. ER -