Nomenclature: δ

Family: GABAA receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates. 

Contents

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 452 1p36.3 GABRD gamma-aminobutyric acid (GABA) A receptor, delta 7,22
Mouse 4 449 4 E2 Gabrd gamma-aminobutyric acid (GABA) A receptor, subunit delta 22
Rat 4 449 5q36 Gabrd gamma-aminobutyric acid (GABA) A receptor, delta 21
Previous and Unofficial Names
GABA(A) receptor, delta
GABAA-RD
MGC105467
GABA(A) receptor subunit delta
GABA-A receptor delta-subunit
GABAA receptor delta subunit
gamma-aminobutyric acid (GABA-A) receptor subunit delta
gamma-aminobutyric acid (GABA-A) receptor, subunit delta
gamma-aminobutyric acid A receptor, delta
gamma-aminobutyric acid receptor subunit delta
AI853201
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
Orphanet Gene
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Natural/Endogenous Ligands
GABA
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
gaboxadol Hs Full agonist - -
[Binds to: GABA site]
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Use-dependent Affinity Units Concentration range (M) Voltage-dependent (mV) Reference
TBPS Hs - no - - - no

Not voltage dependent
picrotoxin Hs - no - - - no

Not voltage dependent
Tissue Distribution
Dentate gyrus granule cells (located perisynaptically on dendrites)
Species:  Mouse
Technique:  Immunocytochemistry
References:  29
Hippocampal interneurons of the dentate molecular layer (assembles with the α1 subunit)
Species:  Mouse
Technique:  Immunohistochemistry, confocal microscopy
References:  9
Thalamic relay nuclei, caudate-putamen, molecular layer of the dentate gyrus, and outer layers of the cerebral cortex
Species:  Mouse
Technique:  Immunohistochemistry
References:  17
Cerebellar granule cells (selective partnering with α6 subunit) shown by loss of δ protein, but not mRNA, in α6 subunit knockout mouse
Species:  Mouse
Technique:  Immunoprecipitation, immunocytochemistry, immunoblot analysis
References:  11
Thalamus(assembles with the α4 subunit)
Species:  Rat
Technique:  Quantitative co-immunoprecipitation
References:  25
Cerebellar granule cells (restricted to extrasynaptic dendritic and somatic membranes)
Species:  Rat
Technique:  Immunohistochemistry
References:  16
Cerebellar granule cells, thalamus relay neurons, dentate gyrus granule cells, caudate-putamen, cortex, olfactory bulb (EP).
Species:  Rat
Technique:  Immunohistochemistry
References:  2,18,20
Medial geniculate thalamic nucleus (MGN)
Species:  Rat
Technique:  In situ hybridization and immunohistochemistry
References:  32
Physiological Consequences of Altering Gene Expression
Mice lacking the δ subunit show reduced sensitivity to neuroactive steroids (Mihalek et al., 1999) and ethanol (Wei et al., 2004; Mihalek et al., 2001), and reduced inhibition in neurons normally expressing the δ subunit (Mihalek et al., 1999; Spigelman et al., 2003; Vicini et al., 2002; Porcello et al., 2003).
Species:  Mouse
Tissue: 
Technique:  Gene knockout
References:  13-14,19,23,26,28,30
Knockout females, but not males, show improved fear conditioning
Species:  Mouse
Tissue:  Nervous system
Technique:  Knockout
References:  15,30
Clinically-Relevant Mutations and Pathophysiology
Disease:  Epilepsy
OMIM:  613060
Orphanet:  36387
Role: 
References:  6
Mutations not determined
Disease:  Chromosome 1p36 deletion syndrome
OMIM:  607872
Orphanet:  1606
References:  31
Mutations not determined
Disease:  Juvenile myoclonic epilepsy
OMIM:  613060
Orphanet:  307
References: 
Mutations not determined
General Comments
Extrasynaptic δ subunit-containing GABAA receptors show distinct pharmacology, including low efficacy to GABA, and high sensitivity to positive modulation by neurosteroids [3,24], ethanol [10,12,27-28] and general anesthetics [1,4-5,8].

REFERENCES

1. Belelli D, Peden DR, Rosahl TW, Wafford KA, Lambert JJ. (2005) Extrasynaptic GABAA receptors of thalamocortical neurons: a molecular target for hypnotics. J. Neurosci.25 (50): 11513-20. [PMID:16354909]

2. Benke D, Mertens S, Trzeciak A, Gillessen D, Mohler H. (1991) Identification and immunohistochemical mapping of GABAA receptor subtypes containing the delta-subunit in rat brain. FEBS Lett.283 (1): 145-9. [PMID:1645294]

3. Bianchi MT, Macdonald RL. (2003) Neurosteroids shift partial agonist activation of GABA(A) receptor channels from low- to high-efficacy gating patterns. J. Neurosci.23 (34): 10934-43. [PMID:14645489]

4. Brown N, Kerby J, Bonnert TP, Whiting PJ, Wafford KA. (2002) Pharmacological characterization of a novel cell line expressing human alpha(4)beta(3)delta GABA(A) receptors. Br. J. Pharmacol.136 (7): 965-74. [PMID:12145096]

5. Caraiscos VB, Newell JG, You-Ten KE, Elliott EM, Rosahl TW, Wafford KA, MacDonald JF, Orser BA. (2004) Selective enhancement of tonic GABAergic inhibition in murine hippocampal neurons by low concentrations of the volatile anesthetic isoflurane. J. Neurosci.24 (39): 8454-8. [PMID:15456818]

6. Dibbens LM, Feng HJ, Richards MC, Harkin LA, Hodgson BL, Scott D, Jenkins M, Petrou S, Sutherland GR, Scheffer IE, Berkovic SF, Macdonald RL, Mulley JC. (2004) GABRD encoding a protein for extra- or peri-synaptic GABAA receptors is a susceptibility locus for generalized epilepsies. Hum. Mol. Genet.13 (13): 1315-9. [PMID:15115768]

7. Emberger W, Windpassinger C, Petek E, Kroisel PM, Wagner K. (2000) Assignment of the human GABAA receptor delta-subunit gene (GABRD) to chromosome band 1p36.3 distal to marker NIB1364 by radiation hybrid mapping. Cytogenet. Cell Genet.89 (3-4): 281-2. [PMID:10965146]

8. Feng HJ, Bianchi MT, Macdonald RL. (2004) Pentobarbital differentially modulates alpha1beta3delta and alpha1beta3gamma2L GABAA receptor currents. Mol. Pharmacol.66 (4): 988-1003. [PMID:15247320]

9. Glykys J, Peng Z, Chandra D, Homanics GE, Houser CR, Mody I. (2007) A new naturally occurring GABA(A) receptor subunit partnership with high sensitivity to ethanol. Nat. Neurosci.10 (1): 40-8. [PMID:17159992]

10. Hanchar HJ, Dodson PD, Olsen RW, Otis TS, Wallner M. (2005) Alcohol-induced motor impairment caused by increased extrasynaptic GABA(A) receptor activity. Nat. Neurosci.8 (3): 339-45. [PMID:15696164]

11. Jones A, Korpi ER, McKernan RM, Pelz R, Nusser Z, Mäkelä R, Mellor JR, Pollard S, Bahn S, Stephenson FA, Randall AD, Sieghart W, Somogyi P, Smith AJ, Wisden W. (1997) Ligand-gated ion channel subunit partnerships: GABAA receptor alpha6 subunit gene inactivation inhibits delta subunit expression. J. Neurosci.17 (4): 1350-62. [PMID:9006978]

12. Liang J, Zhang N, Cagetti E, Houser CR, Olsen RW, Spigelman I. (2006) Chronic intermittent ethanol-induced switch of ethanol actions from extrasynaptic to synaptic hippocampal GABAA receptors. J. Neurosci.26 (6): 1749-58. [PMID:16467523]

13. Mihalek RM, Banerjee PK, Korpi ER, Quinlan JJ, Firestone LL, Mi ZP, Lagenaur C, Tretter V, Sieghart W, Anagnostaras SG, Sage JR, Fanselow MS, Guidotti A, Spigelman I, Li Z, DeLorey TM, Olsen RW, Homanics GE. (1999) Attenuated sensitivity to neuroactive steroids in gamma-aminobutyrate type A receptor delta subunit knockout mice. Proc. Natl. Acad. Sci. U.S.A.96 (22): 12905-10. [PMID:10536021]

14. Mihalek RM, Bowers BJ, Wehner JM, Kralic JE, VanDoren MJ, Morrow AL, Homanics GE. (2001) GABA(A)-receptor delta subunit knockout mice have multiple defects in behavioral responses to ethanol. Alcohol. Clin. Exp. Res.25 (12): 1708-18. [PMID:11781502]

15. Moore MD, Cushman J, Chandra D, Homanics GE, Olsen RW, Fanselow MS. (2010) Trace and contextual fear conditioning is enhanced in mice lacking the alpha4 subunit of the GABA(A) receptor. Neurobiol Learn Mem93 (3): 383-7. [PMID:20018248]

16. Nusser Z, Sieghart W, Somogyi P. (1998) Segregation of different GABAA receptors to synaptic and extrasynaptic membranes of cerebellar granule cells. J. Neurosci.18 (5): 1693-703. [PMID:9464994]

17. Peng Z, Hauer B, Mihalek RM, Homanics GE, Sieghart W, Olsen RW, Houser CR. (2002) GABA(A) receptor changes in delta subunit-deficient mice: altered expression of alpha4 and gamma2 subunits in the forebrain. J. Comp. Neurol.446 (2): 179-97. [PMID:11932935]

18. Pirker S, Schwarzer C, Wieselthaler A, Sieghart W, Sperk G. (2000) GABA(A) receptors: immunocytochemical distribution of 13 subunits in the adult rat brain. Neuroscience101 (4): 815-50. [PMID:11113332]

19. Porcello DM, Huntsman MM, Mihalek RM, Homanics GE, Huguenard JR. (2003) Intact synaptic GABAergic inhibition and altered neurosteroid modulation of thalamic relay neurons in mice lacking delta subunit. J. Neurophysiol.89 (3): 1378-86. [PMID:12626617]

20. Schwarzer C, Berresheim U, Pirker S, Wieselthaler A, Fuchs K, Sieghart W, Sperk G. (2001) Distribution of the major gamma-aminobutyric acid(A) receptor subunits in the basal ganglia and associated limbic brain areas of the adult rat. J. Comp. Neurol.433 (4): 526-49. [PMID:11304716]

21. Shivers BD, Killisch I, Sprengel R, Sontheimer H, Köhler M, Schofield PR, Seeburg PH. (1989) Two novel GABAA receptor subunits exist in distinct neuronal subpopulations. Neuron3 (3): 327-37. [PMID:2561970]

22. Sommer B, Poustka A, Spurr NK, Seeburg PH. (1990) The murine GABAA receptor delta-subunit gene: structure and assignment to human chromosome 1. DNA Cell Biol.9 (8): 561-8. [PMID:2176788]

23. Spigelman I, Li Z, Liang J, Cagetti E, Samzadeh S, Mihalek RM, Homanics GE, Olsen RW. (2003) Reduced inhibition and sensitivity to neurosteroids in hippocampus of mice lacking the GABA(A) receptor delta subunit. J. Neurophysiol.90 (2): 903-10. [PMID:12702713]

24. Stell BM, Brickley SG, Tang CY, Farrant M, Mody I. (2003) Neuroactive steroids reduce neuronal excitability by selectively enhancing tonic inhibition mediated by delta subunit-containing GABAA receptors. Proc. Natl. Acad. Sci. U.S.A.100 (24): 14439-44. [PMID:14623958]

25. Sur C, Farrar SJ, Kerby J, Whiting PJ, Atack JR, McKernan RM. (1999) Preferential coassembly of alpha4 and delta subunits of the gamma-aminobutyric acidA receptor in rat thalamus. Mol. Pharmacol.56 (1): 110-5. [PMID:10385690]

26. Vicini S, Losi G, Homanics GE. (2002) GABA(A) receptor delta subunit deletion prevents neurosteroid modulation of inhibitory synaptic currents in cerebellar neurons. Neuropharmacology43 (4): 646-50. [PMID:12367609]

27. Wallner M, Hanchar HJ, Olsen RW. (2003) Ethanol enhances alpha 4 beta 3 delta and alpha 6 beta 3 delta gamma-aminobutyric acid type A receptors at low concentrations known to affect humans. Proc. Natl. Acad. Sci. U.S.A.100 (25): 15218-23. [PMID:14625373]

28. Wei W, Faria LC, Mody I. (2004) Low ethanol concentrations selectively augment the tonic inhibition mediated by delta subunit-containing GABAA receptors in hippocampal neurons. J. Neurosci.24 (38): 8379-82. [PMID:15385620]

29. Wei W, Zhang N, Peng Z, Houser CR, Mody I. (2003) Perisynaptic localization of delta subunit-containing GABA(A) receptors and their activation by GABA spillover in the mouse dentate gyrus. J. Neurosci.23 (33): 10650-61. [PMID:14627650]

30. Wiltgen BJ, Sanders MJ, Ferguson C, Homanics GE, Fanselow MS. (2005) Trace fear conditioning is enhanced in mice lacking the delta subunit of the GABAA receptor. Learn. Mem.12 (3): 327-33. [PMID:15897254]

31. Windpassinger C, Kroisel PM, Wagner K, Petek E. (2002) The human gamma-aminobutyric acid A receptor delta (GABRD) gene: molecular characterisation and tissue-specific expression. Gene292 (1-2): 25-31. [PMID:12119096]

32. Wisden W, Laurie DJ, Monyer H, Seeburg PH. (1992) The distribution of 13 GABAA receptor subunit mRNAs in the rat brain. I. Telencephalon, diencephalon, mesencephalon. J. Neurosci.12 (3): 1040-62. [PMID:1312131]

To cite this database page, please use the following:

Richard Olsen.
GABAA receptors: δ. Last modified on 17/03/2014. Accessed on 31/10/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=416.

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