KEGG PATHWAY: ko04727

PATHWAY: ko04727

Entry

ko04727 Pathway

Name

GABAergic synapse

Description

Gamma aminobutyric acid (GABA) is the most abundant inhibitory neurotransmitter in the mammalian central nervous system (CNS). When released in the synaptic cleft, GABA binds to three major classes of receptors: GABAA, GABAB, and GABAC receptors. GABAA and GABAC receptors are ionotropic and mediate fast GABA responses by triggering chloride channel openings, while GABAB receptors are metabotropic and mediate slower GABA responses by activating G-proteins and influencing second messenger systems. GABAA receptors, the major sites for fast inhibitory neurotransmission in the CNS, are regulated by phosphorylation mechanisms, affecting both their functional properties and their cell surface mobility and trafficking. GABA release by the presynaptic terminal is negatively regulated by GABAB autoreceptors, and is cleared from the extracellular space by GABA transporters (GATs) located either on the presynaptic terminal or neighboring glial cells.

Class

Organismal Systems; Nervous system

Pathway map

ko04727

GABAergic synapse

Disease

H00746	Hypokalemic periodic paralysis (HypoPP)
H00749	Episodic ataxias
H00775	Familial or sporadic hemiplegic migraine
H00783	Febrile seizures
H00808	Idiopathic generalized epilepsies (IGEs)
H00923	Congenital systemic glutamine deficiency (CSGD)
H01097	Cerebral palsy

Other DBs

BSID:

377129

GO:

0051932

Orthology

K14990	solute carrier family 38 (sodium-coupled neutral amino acid transporter), member 1
K14207	solute carrier family 38 (sodium-coupled neutral amino acid transporter), member 2
K01425	glutaminase [EC:3.5.1.2]
K01580	glutamate decarboxylase [EC:4.1.1.15]
K15015	solute carrier family 32 (vesicular inhibitory amino acid transporter)
K13524	4-aminobutyrate aminotransferase / (S)-3-amino-2-methylpropionate transaminase [EC:2.6.1.22 2.6.1.19]
K05175	gamma-aminobutyric acid receptor subunit alpha
K05181	gamma-aminobutyric acid receptor subunit beta
K05186	gmma-aminobutyric acid receptor subunit gamma
K05184	gamma-aminobutyric acid receptor subunit delta
K05185	gamma-aminobutyric acid receptor subunit epsilon
K05192	gamma-aminobutyric acid receptor subunit theta
K05189	gamma-aminobutyric acid receptor subunit pi
K04345	protein kinase A [EC:2.7.11.11]
K05704	tyrosine-protein kinase Src [EC:2.7.10.2]
K02677	classical protein kinase C [EC:2.7.11.13]
K04647	huntingtin-associated protein 1
K08341	GABA(A) receptor-associated protein (autophagy-related protein 8)
K06027	vesicle-fusing ATPase [EC:3.6.4.6]
K15374	trafficking kinesin-binding protein 2
K15375	inactive phospholipase C-like protein 1
K15376	gephyrin [EC:2.7.7.75 2.10.1.1]
K05190	gamma-aminobutyric acid receptor subunit rho
K04344	voltage-dependent calcium channel P/Q type alpha-1A
K04849	voltage-dependent calcium channel N type alpha-1B
K04850	voltage-dependent calcium channel L type alpha-1C
K04851	voltage-dependent calcium channel L type alpha-1D
K04853	voltage-dependent calcium channel L type alpha-1F
K04857	voltage-dependent calcium channel L type alpha-1S
K04615	gamma-aminobutyric acid type B receptor
K04630	guanine nucleotide-binding protein G(i) subunit alpha
K04534	guanine nucleotide-binding protein G(o) subunit alpha
K04536	guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
K04537	guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2
K07825	guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3
K04538	guanine nucleotide-binding protein subunit beta-4
K04539	guanine nucleotide-binding protein subunit beta-5
K07826	guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
K04540	guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3
K04541	guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4
K04542	guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5
K04543	guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7
K04544	guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8
K04545	guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10
K04546	guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11
K04347	guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12
K04547	guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13
K04548	guanine nucleotide-binding protein G(T) subunit gamma-T1
K04549	guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2
K08041	adenylate cyclase 1 [EC:4.6.1.1]
K08042	adenylate cyclase 2 [EC:4.6.1.1]
K08043	adenylate cyclase 3 [EC:4.6.1.1]
K08044	adenylate cyclase 4 [EC:4.6.1.1]
K08045	adenylate cyclase 5 [EC:4.6.1.1]
K08046	adenylate cyclase 6 [EC:4.6.1.1]
K08047	adenylate cyclase 7 [EC:4.6.1.1]
K08048	adenylate cyclase 8 [EC:4.6.1.1]
K08049	adenylate cyclase 9 [EC:4.6.1.1]
K05000	potassium inwardly-rectifying channel subfamily J member 6
K05034	solute carrier family 6 (neurotransmitter transporter, GABA) member 1
K01915	glutamine synthetase [EC:6.3.1.2]
K13576	solute carrier family 38 (sodium-coupled neutral amino acid transporter), member 3
K14992	solute carrier family 38 (sodium-coupled neutral amino acid transporter), member 5

Compound

C00025	L-Glutamate
C00026	2-Oxoglutarate
C00042	Succinate
C00064	L-Glutamine
C00076	Calcium cation
C00238	Potassium cation
C00334	4-Aminobutanoate
C00575	3',5'-Cyclic AMP
C00698	Cl-

Reference

Authors

Davis KL, Charney D, Coyle JT, Nemeroff C (ed).

Title

Neuropsychopharmacology: The fifth generation of progress

Journal

Lippincott Williams & Wikins (2002)

Reference

PMID:17499109

Authors

Farrant M, Kaila K

Title

The cellular, molecular and ionic basis of GABA(A) receptor signalling.

Journal

Prog Brain Res 160:59-87 (2007)

Reference

PMID:9364667

Authors

Ben-Ari Y, Khazipov R, Leinekugel X, Caillard O, Gaiarsa JL

Title

GABAA, NMDA and AMPA receptors: a developmentally regulated 'menage a trois'.

Journal

Trends Neurosci 20:523-9 (1997)

Reference

PMID:20655485

Authors

Pinard A, Seddik R, Bettler B

Title

GABAB receptors: physiological functions and mechanisms of diversity.

Journal

Adv Pharmacol 58:231-55 (2010)

Reference

PMID:21376567

Authors

Chalifoux JR, Carter AG

Title

GABAB receptor modulation of synaptic function.

Journal

Curr Opin Neurobiol 21:339-44 (2011)

Reference

PMID:20655481

Authors

Padgett CL, Slesinger PA

Title

GABAB receptor coupling to G-proteins and ion channels.

Journal

Adv Pharmacol 58:123-47 (2010)

Reference

PMID:17499108

Authors

Emson PC

Title

GABA(B) receptors: structure and function.

Journal

Prog Brain Res 160:43-57 (2007)

Reference

PMID:16932937

Authors

Kornau HC

Title

GABA(B) receptors and synaptic modulation.

Journal

Cell Tissue Res 326:517-33 (2006)

Reference

PMID:18382465

Authors

Jacob TC, Moss SJ, Jurd R

Title

GABA(A) receptor trafficking and its role in the dynamic modulation of neuronal inhibition.

Journal

Nat Rev Neurosci 9:331-43 (2008)

Reference

PMID:12086709

Authors

Kneussel M

Title

Dynamic regulation of GABA(A) receptors at synaptic sites.

Journal

Brain Res Brain Res Rev 39:74-83 (2002)

Reference

PMID:21555068

Authors

Luscher B, Fuchs T, Kilpatrick CL

Title

GABAA receptor trafficking-mediated plasticity of inhibitory synapses.

Journal

Neuron 70:385-409 (2011)

Reference

PMID:19374920

Authors

Arancibia-Carcamo IL, Kittler JT

Title

Regulation of GABA(A) receptor membrane trafficking and synaptic localization.

Journal

Pharmacol Ther 123:17-31 (2009)

Reference

(Japanese)

Authors

Kanematsu T, Terunuma M, Goto H, Kuratani A, Hirata M.

Title

[The life cycle of the GABAA receptor and its regulating molecules] (In Japanese)

Journal

Folia Pharmacol. Jpn. (Nippon Yakurigaku Sasshi) (2004)

Reference

PMID:16787421

Authors

Bak LK, Schousboe A, Waagepetersen HS

Title

The glutamate/GABA-glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer.

Journal

J Neurochem 98:641-53 (2006)

Reference

PMID:15210304

Authors

Conti F, Minelli A, Melone M

Title

GABA transporters in the mammalian cerebral cortex: localization, development and pathological implications.

Journal

Brain Res Brain Res Rev 45:196-212 (2004)

Reference

PMID:12888801

Authors

Brambilla P, Perez J, Barale F, Schettini G, Soares JC

Title

GABAergic dysfunction in mood disorders.

Journal

Mol Psychiatry 8:721-37, 715 (2003)

Reference

PMID:10780899

Authors

Chebib M, Johnston GA

Title

GABA-Activated ligand gated ion channels: medicinal chemistry and molecular biology.

Journal

J Med Chem 43:1427-47 (2000)

All links

Ontology (2)   
   KEGG BRITE (1)   
   GO (1)   
Pathway (2)   
   KEGG PATHWAY (1)   
   BioSystems (1)   
Disease (7)   
   KEGG DISEASE (7)   
Chemical substance (9)   
   KEGG COMPOUND (9)   
Chemical reaction (12)   
   KEGG ENZYME (12)   
Gene (63)   
   KEGG ORTHOLOGY (63)   
Literature (15)   
   PubMed (15)   
All databases (110)   

Download RDF

DBGET integrated database retrieval system