Nomenclature: ε

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 4 506 Xq28 GABRE gamma-aminobutyric acid (GABA) A receptor, epsilon 2,4,13-14
Mouse 4 916 X A7.3 Gabre gamma-aminobutyric acid (GABA) A receptor, subunit epsilon 10
Rat 4 989 Xq37 Gabre gamma-aminobutyric acid (GABA) A receptor, epsilon 10
Previous and Unofficial Names
GABA(A) receptor, epsilon
GABA(A) receptor subunit epsilon
gamma-aminobutyric acid A receptor, epsilon
gamma-aminobutyric acid (GABA-A) receptor subunit epsilon
gamma-aminobutyric acid (GABA-A) receptor, subunit epsilon
gamma-aminobutyric acid receptor subunit epsilon
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Natural/Endogenous Ligands
GABA
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
Amygdala, thalamus, subthalamic nucleus, spinal cord
Species:  Human
Technique:  Northern blot
References:  2,13
Heart (sino-atrial and atrioventricular nodes, conduction bundle and Purkinje fibres)
Species:  Human
Technique:  In situ hybridisation
References:  4
Locus ceruleus, hypothalamus (ventromedial and dorsomedial areas)
Species:  Rat
Technique:  In situ hybridisation
References:  10
Numerous areas within the diencephalon, mesencephalon, pons, medulla, telencephalon; more restricted distribution within the telencephalon
Species:  Rat
Technique:  In situ hybridisation and immunohistochemistry
References:  7
Hypothalamus (peptidergic neurones)
Species:  Rat
Technique:  In situ hybridisation and immunohistochemistry
References:  8
Hypothalamus (arcuate-ventromedial area with weaker expression in the dorsomedial region), hippocampus (hilus of dentate gyrus)
Species:  Squirrel monkey
Technique:  Immunohistochemistry and in situ hybridisation.
References:  13
Physiological Consequences of Altering Gene Expression
Recombinant expression of the human ε subunit via adenoviral introduction into brainstem neurons innervating the heart caused ablation of pentobarbital-evoked potentiation of inhibitory synaptic currents.
Species:  Rat
Tissue:  Brainstem neurons
Technique:  Adenovirus-mediated transfection
References:  5
Gene Expression and Pathophysiology
Increased expression of the ε subunit has been observed in rats treated with pilocarpine to induce chronic temporal lobe epilepsy.
Tissue or cell type:  Dentate gyrus of the rat hippocampus.
Pathophysiology:  Temporal lobe epilespy
Species:  Rat
Technique:  Single cell RNA amplification
References:  1
Biologically Significant Variant Comments
Although a large ε subunit mRNA transcript (~5.5 - 6.0 kb versus 3.5 kb encoding the mature ε subunit) has been observed in numerous human peripheral tissues [13], it is thought to represent an incompletely spliced species that does not lead to the translation of a GABAA receptor subunit open reading frame [13]. Alternatively, it may represent a distinct mRNA species derived from the GABRE gene that does not express as a protein that can be detected in biochemical and electrophysiological assays [3].

The gene encoding the rodent ε subunit differs from the human ε subunit (εh) gene by virtue of a large nucleotide sequence that encodes a repetitive N-terminal extracellular Pro/Glu motif [10]. In addition to the transcript encoding the long ε subunit variant (εrL) a subsequent study additionally identified a transcript encoding a short variant (εr) similar to &epsilonh [7]. Electrophysiological studies suggest that the εr but not εrL subunit may incorporate into functional GABAAreceptors [3].
General Comments
The ε subunit confers distinguishing biophysical and pharmacological properties to recombinant GABAA receptors. GABAA receptors containing the ε subunit exhibit a relatively high level of picrotoxin inhibited spontaneous gating and have distinguishable desensitization kinetics [9,12]. The ε subunit reduces positive modulation of GABAA receptors by propofol and anaesthetic steroids and does not support the binding of the benzodiazepines flunitrazepam, or flumazenil [2]. The stoichiometry of epsilon subunit-containing receptors remains unresolved. It has been suggested that certain properties, such as anaesthetic sensitivity and spontaneous gating, may relate to the number of ε subunits assembled with α and β subunits in functional receptors [6,11]. However, there has been no demonstration of such variable stoichiometry using direct approaches.

REFERENCES

1. Brooks-Kayal AR, Shumate MD, Jin H, Rikhter TY, Coulter DA. (1998) Selective changes in single cell GABA(A) receptor subunit expression and function in temporal lobe epilepsy. Nat. Med.4 (10): 1166-72. [PMID:9771750]

2. Davies PA, Hanna MC, Hales TG, Kirkness EF. (1997) Insensitivity to anaesthetic agents conferred by a class of GABA(A) receptor subunit. Nature385 (6619): 820-3. [PMID:9039914]

3. Davies PA, McCartney MR, Wang W, Hales TG, Kirkness EF. (2002) Alternative transcripts of the GABA(A) receptor epsilon subunit in human and rat. Neuropharmacology43 (4): 467-75. [PMID:12367593]

4. Garret M, Bascles L, Boue-Grabot E, Sartor P, Charron G, Bloch B, Margolskee RF. (1997) An mRNA encoding a putative GABA-gated chloride channel is expressed in the human cardiac conduction system. J. Neurochem.68 (4): 1382-9. [PMID:9084408]

5. Irnaten M, Walwyn WM, Wang J, Venkatesan P, Evans C, Chang KS, Andresen MC, Hales TG, Mendelowitz D. (2002) Pentobarbital enhances GABAergic neurotransmission to cardiac parasympathetic neurons, which is prevented by expression of GABA(A) epsilon subunit. Anesthesiology97 (3): 717-24. [PMID:12218540]

6. Jones BL, Henderson LP. (2007) Trafficking and potential assembly patterns of epsilon-containing GABAA receptors. J. Neurochem.103 (3): 1258-71. [PMID:17714454]

7. Moragues N, Ciofi P, Lafon P, Odessa MF, Tramu G, Garret M. (2000) cDNA cloning and expression of a gamma-aminobutyric acid A receptor epsilon-subunit in rat brain. Eur. J. Neurosci.12 (12): 4318-30. [PMID:11122342]

8. Moragues N, Ciofi P, Lafon P, Tramu G, Garret M. (2003) GABAA receptor epsilon subunit expression in identified peptidergic neurons of the rat hypothalamus. Brain Res.967 (1-2): 285-9. [PMID:12650990]

9. Neelands TR, Fisher JL, Bianchi M, Macdonald RL. (1999) Spontaneous and gamma-aminobutyric acid (GABA)-activated GABA(A) receptor channels formed by epsilon subunit-containing isoforms. Mol. Pharmacol.55 (1): 168-78. [PMID:9882711]

10. Sinkkonen ST, Hanna MC, Kirkness EF, Korpi ER. (2000) GABA(A) receptor epsilon and theta subunits display unusual structural variation between species and are enriched in the rat locus ceruleus. J. Neurosci.20 (10): 3588-95. [PMID:10804200]

11. Thompson SA, Bonnert TP, Cagetti E, Whiting PJ, Wafford KA. (2002) Overexpression of the GABA(A) receptor epsilon subunit results in insensitivity to anaesthetics. Neuropharmacology43 (4): 662-8. [PMID:12367611]

12. Wagner DA, Goldschen-Ohm MP, Hales TG, Jones MV. (2005) Kinetics and spontaneous open probability conferred by the epsilon subunit of the GABAA receptor. J. Neurosci.25 (45): 10462-8. [PMID:16280584]

13. Whiting PJ, McAllister G, Vassilatis D, Bonnert TP, Heavens RP, Smith DW, Hewson L, O'Donnell R, Rigby MR, Sirinathsinghji DJ, Marshall G, Thompson SA, Wafford KA, Vasilatis D. (1997) Neuronally restricted RNA splicing regulates the expression of a novel GABAA receptor subunit conferring atypical functional properties [corrected; erratum to be published]. J. Neurosci.17 (13): 5027-37. [PMID:9185540]

14. Wilke K, Gaul R, Klauck SM, Poustka A. (1997) A gene in human chromosome band Xq28 (GABRE) defines a putative new subunit class of the GABAA neurotransmitter receptor. Genomics45 (1): 1-10. [PMID:9339354]

To cite this database page, please use the following:

Tim G. Hales, John A. Peters.
GABAA receptors: ε. Last modified on 14/03/2014. Accessed on 25/10/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=417.

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