Desensitization of homomeric alpha1 glycine receptor increases with receptor density.
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 GlyRalpha1 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 GlyRalpha1 bearing the gephyrin-binding site with gephyrin also increased desensitization but at 1 day after transfection compared with transfections of homomeric GlyRalpha1 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 EC(50) 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.
Legendre
Pascal
P
Unité Mixte Recherche Centre National de la Recherche Scientifique 7102, Université Pierre et Marie Curie, Paris, France. pasal.legendre@snv.jussieu.fr
Muller
Emilie
E
Badiu
Carmen Ionela
CI
Meier
Jochen
J
Vannier
Christian
C
Triller
Antoine
A
D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D015870:Gene Expression; D005998:Glycine / Q000378:metabolism*; D006801:Humans; D018009:Receptors, Glycine / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D013997:Time Factors; D014162:Transfection
D018009:Receptors, Glycine; D005998:Glycine