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

ε

Family: GABAA receptors

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Tissue Distribution
Physiological Consequences of Altering Gene Expression
Gene Expression and Pathophysiology
Biologically Significant Variants
General Comments
References
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 10228 (Hs)
Ensembl ENSG00000102287 (Hs), ENSMUSG00000031340 (Mm), ENSRNOG00000016533 (Rn)
Entrez Gene 2564 (Hs), 14404 (Mm), 65191 (Rn)
GeneCards GABRE (Hs)
GenitoUrinary Development Molecular Anatomy Project Gabre (Mm)
HomoloGene 68425 (Hs)
Human Protein Reference Database 02104 (Hs)
InterPro P78334 (Hs), Q9ES14 (Rn)
KEGG Gene hsa:2564 (Hs), mmu:14404 (Mm), rno:65191 (Rn)
OMIM 300093 (Hs)
PharmGKB Gene PA28499 (Hs)
PhosphoSitePlus P78334 (Hs), O88966 (Mm)
Protein Ontology (PRO) PRO:000007776 (Hs)
RefSeq Nucleotide NM_004961 (Hs), NM_017369 (Mm), NM_023091 (Rn)
RefSeq Protein NP_004952 (Hs), NP_059065 (Mm), NP_075579 (Rn)
TreeFam ENSG00000102287 (Hs), ENSMUSG00000031340 (Mm), ENSRNOG00000016533 (Rn)
UniGene Hs. 22785 (Hs)
UniProt P78334 (Hs), Q9ES14 (Rn)
Wikipedia ε
GABAA receptors
Search for 3D structures on the PDB
Search by keyword: GABAA receptors ε Search by accession number: P78334, Q9ES14
Natural/Endogenous Ligand(s)
GABA
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
Hypothalamus (peptidergic neurones)
Species:  Rat
Technique:  In situ hybridisation and immunohistochemistry
References:  8
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 (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

Show »

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. Nature, 385 (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. Neuropharmacology, 43 (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. Anesthesiology, 97 (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. Neuropharmacology, 43 (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. Genomics, 45 (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 11/10/2012. Accessed on 19/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=417.


Contact us | Print | Back to top | Help