title: Glycinergic and GABAergic synaptic transmission are differentially affected by gephyrin in spinal neurons.
abstract: In the present study, we have examined the physiological properties of synaptic currents mediated by GlyRs and GABAARs after culturing spinal neurons with a gephyrin antisense oligonucleotide. Application of gephyrin antisense, but not the sense, reduced the glycinergic mIPSC amplitude ( approximately 50%) and frequency ( approximately 85%), indicating the importance of gephyrin for GlyR anchoring at postsynaptic sites. On the other hand, the glycine-evoked current amplitude was unchanged indicating that functional GlyRs were still located in the extrasynaptic membrane. The analysis of the GABAergic transmission in the same neurons revealed approximately 70% reduction in the frequency of the GABAergic mIPSCs, without changes in the amplitude. Interestingly, the modulation of remaining GABAAR-mediated synaptic events by zinc and diazepam was significantly altered by the antisense. These results indicate that gephyrin is required for the membrane insertion/stabilization of the GABAAR gamma2 subunit as well as for its subsequent localization in the postsynaptic membrane.
authors.affiliation: Department of Physiology, University of Concepción, Laboratory of Neurophysiology, P.O. Box 160-C, Concepción, Chile.
authors.forename: Brigitte
authors.initials: B
authors.lastname: van Zundert
authors.forename: Patricio
authors.initials: P
authors.lastname: Castro
authors.forename: Luis G
authors.initials: LG
authors.lastname: Aguayo
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D005333:Fetus / Q000166:cytology; D005998:Glycine / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D021122:Protein Subunits / Q000502:physiology*; D011963:Receptors, GABA-A / Q000502:physiology*; D018009:Receptors, Glycine / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D002352:Carrier Proteins; C546280:Gabrg2 protein, mouse; D008565:Membrane Proteins; D016376:Oligonucleotides, Antisense; D021122:Protein Subunits; D011963:Receptors, GABA-A; D018009:Receptors, Glycine; C073441:gephyrin; D005680:gamma-Aminobutyric Acid; D005998:Glycine