KEGG   PATHWAY: hsa04727Help
Entry
hsa04727                    Pathway                                

Name
GABAergic synapse - Homo sapiens (human)
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
BRITE hierarchy
Pathway map
GABAergic synapse
hsa04727

All organismsOrtholog table
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
Drug
D00058  
gamma-Aminobutyric acid (JAN)
D00225  
Alprazolam (JP16/USP/INN)
D00241  
Baclofen (JP16/USP/INN)
D00267  
Chlordiazepoxide (JP16/USP/INN)
D00280  
Clonazepam (JP16/USP/INN)
D00293  
Diazepam (JP16/USP/INN)
D00304  
Divalproex sodium (USP)
D00311  
Estazolam (JP16/USAN/INN)
D00329  
Flurazepam (JAN/INN)
D00331  
Furosemide (JP16/USP/INN)
D00365  
Lorazepam (JP16/USP/INN)
D00370  
Temazepam (USP/INN)
D00376  
Meprobamate (JAN/USP/INN)
D00387  
Triazolam (JAN/USP/INN)
D00399  
Valproic acid (USP)
D00430  
Secobarbital (USP/INN)
D00457  
Quazepam (JAN/USP/INN)
D00470  
Prazepam (JP16/USAN/INN)
D00499  
Pentobarbital (USP/INN)
D00500  
Pentobarbital sodium (JAN/USP)
D00506  
Phenobarbital (JP16/USP/INN)
D00531  
Nitrazepam (JP16/USAN/INN)
D00532  
Glutethimide (JAN/INN)
D00535  
Vigabatrin (JAN/USAN/INN)
D00537  
Topiramate (JAN/USAN/INN)
D00549  
Propofol (JAN/USAN/INN)
D00550  
Midazolam (JAN/USP/INN)
D00555  
Amobarbital (JP16/INN)
D00557  
Methaqualone (JAN/USAN/INN)
D00693  
Chlordiazepoxide hydrochloride (JAN/USP)
D00694  
Clorazepate dipotassium (JP16/USP)
D00695  
Flurazepam hydrochloride (USP)
D00696  
Midazolam hydrochloride (USAN)
D00697  
Flumazenil (JAN/USP/INN)
D00700  
Mephobarbital (JAN/USP)
D00701  
Phenobarbital sodium (JAN/USP/INN)
D00706  
Zolpidem tartrate (JP16/USAN)
D00710  
Sodium valproate (JP16)
D00713  
Thiamylal sodium (JP16)
D00714  
Thiopental sodium (JP16/USP/INN)
D01071  
Hexobarbital (JAN/INN)
D01230  
Flunitrazepam (JP16/USAN/INN)
D01245  
Bromazepam (JP16/USAN/INN)
D01253  
Clobazam (JAN/USAN/INN)
D01254  
Tofisopam (JP16/INN)
D01268  
Cloxazolam (JP16/INN)
D01278  
Oxazolam (JP16/INN)
D01279  
Flutoprazepam (JP16/INN)
D01286  
Flutazolam (JAN/INN)
D01292  
Medazepam (JP16/INN)
D01293  
Ethyl loflazepate (JAN/INN)
D01310  
Secobarbital sodium (JAN/USP)
D01316  
Mexazolam (JAN/INN)
D01328  
Clotiazepam (JP16/INN)
D01354  
Fludiazepam (JP16/INN)
D01372  
Zopiclone (JAN/INN)
D01408  
Flurazepam hydrochloride (JP16)
D01514  
Etizolam (JP16/INN)
D01564  
Rilmazafone hydrochloride hydrate (JAN)
D01593  
Nimetazepam (JAN/INN)
D01657  
Lormetazepam (JAN/USAN/INN)
D01740  
Barbital (JP16/INN)
D01744  
Brotizolam (JP16/USAN/INN)
D01758  
Haloxazolam (JP16/INN)
D02097  
Tiagabine hydrochloride (USP)
D02252  
Amobarbital sodium (JAN/USP)
D02253  
Pentobarbital calcium (JP16)
D02283  
Iomazenil (123I) (JAN/INN)
D02594  
Abecarnil (INN)
D02616  
Pagoclone (USAN/INN)
D02617  
Ocinaplon (USAN/INN)
D02624  
Eszopiclone (JAN/USAN/INN)
D03155  
Bretazenil (USAN/INN)
D03562  
Clorazepate monopotassium (USAN)
D03737  
Dextofisopam (USAN/INN)
D04257  
Fospropofol disodium (USAN)
D04282  
Gaboxadol (USAN/INN)
D04300  
Ganaxolone (USAN/INN)
D04721  
Levotofisopam (USAN/INN)
D04882  
Medazepam hydrochloride (USAN)
D05028  
Midazolam maleate (USAN)
D06106  
Thiamylal
D06363  
Ziconotide (USAN/INN)
D07326  
Loprazolam (INN)
D07409  
Pentetrazol (INN)
D07784  
Delorazepam (INN)
D07999  
Sodium furosemide
D08001  
Furosemide diolamine
D08145  
Loprazolam mesilate
D08283  
Nordazepam (INN)
D08356  
Phenobarbital diethylamine
D08481  
Rilmazafone (INN)
D08507  
Sarmazenil (INN)
D08588  
Tiagabine (INN)
D08667  
Calcium valproate
D08686  
Ziconotide acetate
D08690  
Zolpidem (INN)
D08840  
Adipiplon (USAN)
D08861  
Arbaclofen placarbil (USAN/INN)
D09791  
Arbaclofen (USAN)
D10194  
Remimazolam besilate (JAN)
Other DBs
BSID: 
GO: 
Organism
Homo sapiens (human) [GN:hsa]
Gene
81539  
SLC38A1; solute carrier family 38, member 1 [KO:K14990]
54407  
SLC38A2; solute carrier family 38, member 2 [KO:K14207]
27165  
GLS2; glutaminase 2 (liver, mitochondrial) [KO:K01425] [EC:3.5.1.2]
2744  
GLS; glutaminase [KO:K01425] [EC:3.5.1.2]
2571  
GAD1; glutamate decarboxylase 1 (brain, 67kDa) [KO:K01580] [EC:4.1.1.15]
2572  
GAD2; glutamate decarboxylase 2 (pancreatic islets and brain, 65kDa) [KO:K01580] [EC:4.1.1.15]
140679  
SLC32A1; solute carrier family 32 (GABA vesicular transporter), member 1 [KO:K15015]
18  
ABAT; 4-aminobutyrate aminotransferase [KO:K13524] [EC:2.6.1.22 2.6.1.19]
2554  
GABRA1; gamma-aminobutyric acid (GABA) A receptor, alpha 1 [KO:K05175]
2555  
GABRA2; gamma-aminobutyric acid (GABA) A receptor, alpha 2 [KO:K05175]
2556  
GABRA3; gamma-aminobutyric acid (GABA) A receptor, alpha 3 [KO:K05175]
2557  
GABRA4; gamma-aminobutyric acid (GABA) A receptor, alpha 4 [KO:K05175]
2558  
GABRA5; gamma-aminobutyric acid (GABA) A receptor, alpha 5 [KO:K05175]
2559  
GABRA6; gamma-aminobutyric acid (GABA) A receptor, alpha 6 [KO:K05175]
2560  
GABRB1; gamma-aminobutyric acid (GABA) A receptor, beta 1 [KO:K05181]
2562  
GABRB3; gamma-aminobutyric acid (GABA) A receptor, beta 3 [KO:K05181]
2561  
GABRB2; gamma-aminobutyric acid (GABA) A receptor, beta 2 [KO:K05181]
2565  
GABRG1; gamma-aminobutyric acid (GABA) A receptor, gamma 1 [KO:K05186]
2566  
GABRG2; gamma-aminobutyric acid (GABA) A receptor, gamma 2 [KO:K05186]
2567  
GABRG3; gamma-aminobutyric acid (GABA) A receptor, gamma 3 [KO:K05186]
2563  
GABRD; gamma-aminobutyric acid (GABA) A receptor, delta [KO:K05184]
2564  
GABRE; gamma-aminobutyric acid (GABA) A receptor, epsilon [KO:K05185]
55879  
GABRQ; gamma-aminobutyric acid (GABA) A receptor, theta [KO:K05192]
2568  
GABRP; gamma-aminobutyric acid (GABA) A receptor, pi [KO:K05189]
5566  
PRKACA; protein kinase, cAMP-dependent, catalytic, alpha [KO:K04345] [EC:2.7.11.11]
5567  
PRKACB; protein kinase, cAMP-dependent, catalytic, beta [KO:K04345] [EC:2.7.11.11]
5568  
PRKACG; protein kinase, cAMP-dependent, catalytic, gamma [KO:K04345] [EC:2.7.11.11]
5613  
PRKX; protein kinase, X-linked [KO:K04345] [EC:2.7.11.11]
6714  
SRC; v-src avian sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog [KO:K05704] [EC:2.7.10.2]
5578  
PRKCA; protein kinase C, alpha [KO:K02677] [EC:2.7.11.13]
5579  
PRKCB; protein kinase C, beta [KO:K02677] [EC:2.7.11.13]
5582  
PRKCG; protein kinase C, gamma [KO:K02677] [EC:2.7.11.13]
9001  
HAP1; huntingtin-associated protein 1 [KO:K04647]
11337  
GABARAP; GABA(A) receptor-associated protein [KO:K08341]
23710  
GABARAPL1; GABA(A) receptor-associated protein like 1 [KO:K08341]
11345  
GABARAPL2; GABA(A) receptor-associated protein-like 2 [KO:K08341]
4905  
NSF; N-ethylmaleimide-sensitive factor [KO:K06027] [EC:3.6.4.6]
66008  
TRAK2; trafficking protein, kinesin binding 2 [KO:K15374]
5334  
PLCL1; phospholipase C-like 1 [KO:K15375]
10243  
GPHN; gephyrin [KO:K15376] [EC:2.7.7.75 2.10.1.1]
2569  
GABRR1; gamma-aminobutyric acid (GABA) A receptor, rho 1 [KO:K05190]
2570  
GABRR2; gamma-aminobutyric acid (GABA) A receptor, rho 2 [KO:K05190]
200959  
GABRR3; gamma-aminobutyric acid (GABA) A receptor, rho 3 [KO:K05190]
773  
CACNA1A; calcium channel, voltage-dependent, P/Q type, alpha 1A subunit [KO:K04344]
774  
CACNA1B; calcium channel, voltage-dependent, N type, alpha 1B subunit [KO:K04849]
775  
CACNA1C; calcium channel, voltage-dependent, L type, alpha 1C subunit [KO:K04850]
776  
CACNA1D; calcium channel, voltage-dependent, L type, alpha 1D subunit [KO:K04851]
778  
CACNA1F; calcium channel, voltage-dependent, L type, alpha 1F subunit [KO:K04853]
779  
CACNA1S; calcium channel, voltage-dependent, L type, alpha 1S subunit [KO:K04857]
2550  
GABBR1; gamma-aminobutyric acid (GABA) B receptor, 1 [KO:K04615]
9568  
GABBR2; gamma-aminobutyric acid (GABA) B receptor, 2 [KO:K04615]
2770  
GNAI1; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 1 [KO:K04630]
2773  
GNAI3; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 3 [KO:K04630]
2771  
GNAI2; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 2 [KO:K04630]
2775  
GNAO1; guanine nucleotide binding protein (G protein), alpha activating activity polypeptide O [KO:K04534]
2782  
GNB1; guanine nucleotide binding protein (G protein), beta polypeptide 1 [KO:K04536]
2783  
GNB2; guanine nucleotide binding protein (G protein), beta polypeptide 2 [KO:K04537]
2784  
GNB3; guanine nucleotide binding protein (G protein), beta polypeptide 3 [KO:K07825]
59345  
GNB4; guanine nucleotide binding protein (G protein), beta polypeptide 4 [KO:K04538]
10681  
GNB5; guanine nucleotide binding protein (G protein), beta 5 [KO:K04539]
54331  
GNG2; guanine nucleotide binding protein (G protein), gamma 2 [KO:K07826]
2785  
GNG3; guanine nucleotide binding protein (G protein), gamma 3 [KO:K04540]
2786  
GNG4; guanine nucleotide binding protein (G protein), gamma 4 [KO:K04541]
2787  
GNG5; guanine nucleotide binding protein (G protein), gamma 5 [KO:K04542]
2788  
GNG7; guanine nucleotide binding protein (G protein), gamma 7 [KO:K04543]
94235  
GNG8; guanine nucleotide binding protein (G protein), gamma 8 [KO:K04544]
2790  
GNG10; guanine nucleotide binding protein (G protein), gamma 10 [KO:K04545]
2791  
GNG11; guanine nucleotide binding protein (G protein), gamma 11 [KO:K04546]
55970  
GNG12; guanine nucleotide binding protein (G protein), gamma 12 [KO:K04347]
648044  
guanine nucleotide binding protein (G protein); K04347 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347]
51764  
GNG13; guanine nucleotide binding protein (G protein), gamma 13 [KO:K04547]
2792  
GNGT1; guanine nucleotide binding protein (G protein), gamma transducing activity polypeptide 1 [KO:K04548]
2793  
GNGT2; guanine nucleotide binding protein (G protein), gamma transducing activity polypeptide 2 [KO:K04549]
107  
ADCY1; adenylate cyclase 1 (brain) [KO:K08041] [EC:4.6.1.1]
108  
ADCY2; adenylate cyclase 2 (brain) [KO:K08042] [EC:4.6.1.1]
109  
ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
196883  
ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
111  
ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
112  
ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
113  
ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
114  
ADCY8; adenylate cyclase 8 (brain) [KO:K08048] [EC:4.6.1.1]
115  
ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
3763  
KCNJ6; potassium inwardly-rectifying channel, subfamily J, member 6 [KO:K05000]
6529  
SLC6A1; solute carrier family 6 (neurotransmitter transporter), member 1 [KO:K05034]
2752  
GLUL; glutamate-ammonia ligase [KO:K01915] [EC:6.3.1.2]
10991  
SLC38A3; solute carrier family 38, member 3 [KO:K13576]
92745  
SLC38A5; solute carrier family 38, member 5 [KO:K14992]
57468  
SLC12A5; solute carrier family 12 (potassium/chloride transporter), member 5 [KO:K14427]
6538  
SLC6A11; solute carrier family 6 (neurotransmitter transporter), member 11 [KO:K05039]
6540  
SLC6A13; solute carrier family 6 (neurotransmitter transporter), member 13 [KO:K05039]
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
  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
  Authors
Pinard A, Seddik R, Bettler B
  Title
GABAB receptors: physiological functions and mechanisms of diversity.
  Journal
Adv Pharmacol 58:231-55 (2010)
Reference
  Authors
Chalifoux JR, Carter AG
  Title
GABAB receptor modulation of synaptic function.
  Journal
Curr Opin Neurobiol 21:339-44 (2011)
Reference
  Authors
Padgett CL, Slesinger PA
  Title
GABAB receptor coupling to G-proteins and ion channels.
  Journal
Adv Pharmacol 58:123-47 (2010)
Reference
  Authors
Emson PC
  Title
GABA(B) receptors: structure and function.
  Journal
Prog Brain Res 160:43-57 (2007)
Reference
  Authors
Kornau HC
  Title
GABA(B) receptors and synaptic modulation.
  Journal
Cell Tissue Res 326:517-33 (2006)
Reference
  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
  Authors
Kneussel M
  Title
Dynamic regulation of GABA(A) receptors at synaptic sites.
  Journal
Brain Res Brain Res Rev 39:74-83 (2002)
Reference
  Authors
Luscher B, Fuchs T, Kilpatrick CL
  Title
GABAA receptor trafficking-mediated plasticity of inhibitory synapses.
  Journal
Neuron 70:385-409 (2011)
Reference
  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
  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
  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
  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
  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)
KO pathway
 

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