RT Journal Article
SR Electronic
T1 Desensitization of Homomeric α1 Glycine Receptor Increases with Receptor Density
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 817
OP 827
DO 10.1124/mol.62.4.817
VO 62
IS 4
A1 Legendre, Pascal
A1 Muller, Emilie
A1 Badiu, Carmen Ionela
A1 Meier, Jochen
A1 Vannier, Christian
A1 Triller, Antoine
YR 2002
UL http://molpharm.aspetjournals.org/content/62/4/817.abstract
AB 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.