| Annotated protein: | Gamma-aminobutyric acid receptor subunit delta (GABA(A) receptor subunit delta). Gene symbol: GABRD. Taxonomy: Mus musculus (Mouse). Uniprot ID: P22933 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ GABRD |
| Ontology domain: | Biological Process |
| SynGO term: | transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential (GO:1904315) |
| Synapse type(s): | hippocampus, GABAergic |
| Annotated paper: | Wei W, et al. "Perisynaptic localization of delta subunit-containing GABA(A) receptors and their activation by GABA spillover in the mouse dentate gyrus" J Neurosci. 2003 Nov 19;23(33):10650-61 PMID:14627650 |
| Figure(s): | Fig.3, 5-7 |
| Annotation description: | Background: as far as I could find the GABRD is part of GABARs that are located at extra synaptic sites. This paper is an example of the functional role of delta subunit containing GABARs for synaptic transmission via activation via GABA that spills over after excessive presynaptic stimulation. One of the characteristics of the delta subunit is Zn2+ sensitivity. The temperature is used as an experimental variable since at low temp the re-uptake of GABA is perturbed, whereas at higher temp the uptake is ok. Fig.3: "sIPSC conductance and voltage dependence of τw in wt and δ-/- granule cells" - Literal: " This shows that transmembrane voltage does not change the characteristics of GABAA receptor-mediated sIPSC amplitude and decay shaping." Shows that KO of GABRD does not affect the properties of sIPSC Fig.5: "The effect of Zn2+ on sIPSC kinetics in wt and δ-/-. A, At 34°C, ZnCl2 (10 μm) had no significant effect on the decay time constants of sIPSCs recorded in either wt (n = 5) or δ-/- (n = 6) granule cells." When GABA uptake is ok, then there is no effect of Zn2+ since the GABRD receptors do not get activated via spillover. Fig.6: "The effect of Zn2+ on eIPSCs elicited from somatic and dendritic stimulation sites in wt and δ-/- granule cells" Fig.7: "Effect of the GAT-1 GABA transporter inhibitor NO711 (10 μm) on somatically and dendritically elicited eIPSCs in wt and δ-/- granule cells" The pharmacological block of GABA import has an effect on IPSCs in the wt but not in the δ-/- cells. Summary by the authors: "The main findings of our study are as follows: (1) in granule cells of the mouse dentate gyrus, δ subunit-containing GABAA receptors are localized predominantly at the edge of symmetric synapses on dendrites in the molecular layer, and (2) at near-physiological temperature, these receptors do not participate in shaping sIPSCs unless GABA overspill occurs when the GAT-1-dependent GABA uptake system is impaired or when large amounts of GABA are released from inhibitory terminals. This very specific localization together with a high Zn2+ sensitivity endows these receptors with a special role in regulating the excitability of granule cells." |
| Evidence tracking, Biological System: | Intact tissue |
| Evidence tracking, Protein Targeting: | Genetic transformation (eg; knockout, knockin, mutations) |
| Evidence tracking, Experiment Assay: | Whole-cell patch clamp |
| Annotator(s): | Pim van Nierop (ORCID:0000-0003-0593-3443) Guus Smit (ORCID:0000-0002-2286-1587) Matthijs Verhage (ORCID:0000-0002-2514-0216) |
| Lab: | Department of Functional Genomics, Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands |
| SynGO annotation ID: | 2260 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |