Page last updated: 2024-10-24

gamma-aminobutyric acid:sodium:chloride symporter activity

Definition

Target type: molecularfunction

Enables the transfer of a solute or solutes from one side of a membrane to the other according to the reaction: gamma-aminobutyric acid(out) + Na+(out) + Cl-(out) = gamma-aminobutyric acid(in) + Na+(in) + Cl(in). [PMID:7589472, PMID:7861179]

Gamma-aminobutyric acid (GABA):sodium:chloride symporter activity is a crucial process in the nervous system responsible for the reuptake of GABA, the primary inhibitory neurotransmitter in the brain. This process is critical for maintaining normal brain function and preventing neuronal hyperexcitability.

The GABA:sodium:chloride symporter is a transmembrane protein that facilitates the simultaneous movement of one GABA molecule, two sodium ions (Na+), and one chloride ion (Cl-) across the neuronal membrane. This movement occurs in the same direction, from the synaptic cleft (the space between neurons) into the presynaptic neuron.

The process begins with the binding of GABA to the symporter, which initiates a conformational change in the protein, allowing the entry of sodium and chloride ions. The electrochemical gradient of sodium ions drives the transport of GABA, chloride, and sodium into the neuron. Once inside the neuron, GABA is packaged into vesicles for subsequent release at the synapse.

The reuptake of GABA by this symporter plays a vital role in terminating the inhibitory signal at the synapse. By removing GABA from the synaptic cleft, the symporter prevents prolonged activation of GABA receptors, thus ensuring precise control of neuronal activity.

Several factors can influence the activity of the GABA:sodium:chloride symporter, including the concentration of GABA, sodium, and chloride ions, as well as the presence of specific medications. Drugs that inhibit the activity of this symporter, such as tiagabine, can increase GABA levels in the synaptic cleft, leading to enhanced inhibitory neurotransmission.

In summary, the GABA:sodium:chloride symporter activity is a fundamental process in the nervous system that controls the reuptake of GABA, ensuring proper neuronal inhibition and regulating brain function.'
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Proteins (9)

ProteinDefinitionTaxonomy
Sodium- and chloride-dependent GABA transporter 2A sodium- and chloride-dependent GABA transporter 2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9NSD5]Homo sapiens (human)
Sodium- and chloride-dependent GABA transporter 3A sodium- and chloride-dependent GABA transporter 3 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P48066]Homo sapiens (human)
Sodium- and chloride-dependent GABA transporter 1A sodium- and chloride-dependent GABA transporter 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P30531]Homo sapiens (human)
Sodium- and chloride-dependent creatine transporter 1A sodium- and chloride-dependent creatine transporter 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P48029]Homo sapiens (human)
Sodium- and chloride-dependent GABA transporter 2A sodium- and chloride-dependent GABA transporter 2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9NSD5]Homo sapiens (human)
Sodium- and chloride-dependent GABA transporter 3A sodium- and chloride-dependent GABA transporter 3 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P48066]Homo sapiens (human)
Sodium- and chloride-dependent betaine transporterA sodium- and chloride-dependent betaine transporter that is encoded in the genome of human. [PRO:DNx, UniProtKB:P48065]Homo sapiens (human)
Sodium- and chloride-dependent taurine transporterA sodium- and chloride-dependent taurine transporter that is encoded in the genome of human. [PRO:DNx, UniProtKB:P31641]Homo sapiens (human)
Sodium- and chloride-dependent GABA transporter 1A sodium- and chloride-dependent GABA transporter 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P30531]Homo sapiens (human)

Compounds (20)

CompoundDefinitionClassesRoles
gamma-aminobutyric acidgamma-aminobutyric acid : A gamma-amino acid that is butanoic acid with the amino substituent located at C-4.

gamma-Aminobutyric Acid: The most common inhibitory neurotransmitter in the central nervous system.
amino acid zwitterion;
gamma-amino acid;
monocarboxylic acid
human metabolite;
neurotransmitter;
Saccharomyces cerevisiae metabolite;
signalling molecule
beta-alanineamino acid zwitterion;
beta-amino acid
agonist;
fundamental metabolite;
human metabolite;
inhibitor;
neurotransmitter
2,3-diaminopropionic acid3-aminoalanine : A diamino acid that is alanine in which one of the hydrogens of the methyl group is replaced by an amino group.alanine derivative;
amino acid zwitterion;
beta-amino acid;
diamino acid;
non-proteinogenic alpha-amino acid
Escherichia coli metabolite
creatineglycine derivative;
guanidines;
zwitterion
geroprotector;
human metabolite;
mouse metabolite;
neuroprotective agent;
nutraceutical
taurineamino sulfonic acid;
zwitterion
antioxidant;
Escherichia coli metabolite;
glycine receptor agonist;
human metabolite;
mouse metabolite;
nutrient;
radical scavenger;
Saccharomyces cerevisiae metabolite
guvacineguvacine : A alpha,beta-unsaturated monocarboxylic acid that is nicotinic acid which has been hydrogenated at the 1-2 and 5-6 positions of the pyridine ring.

guvacine: RN given refers to parent cpd
alpha,beta-unsaturated monocarboxylic acid;
beta-amino acid;
pyridine alkaloid;
secondary amino compound;
tetrahydropyridine
GABA reuptake inhibitor;
plant metabolite
nipecotic acidnipecotic acid : A piperidinemonocarboxylic acid that is piperidine in which one of the hydrogens at position 3 is substituted by a carboxylic acid group.

nipecotic acid: RN given refers to cpd without isomeric designation
beta-amino acid;
piperidinemonocarboxylic acid
tiagabinetiagabine : A piperidinemonocarboxylic acid that is (R)-nipecotic acid in which the hydrogen attached to the nitrogen has been replaced by a 1,1-bis(3-methyl-2-thienyl)but-1-en-4-yl group. A GABA reuptake inhibitor, it is used (generally as the hydrochloride salt) for the treatment of epilepsy.

Tiagabine: A nipecotic acid derivative that acts as a GABA uptake inhibitor and anticonvulsant agent. It is used in the treatment of EPILEPSY, for refractory PARTIAL SEIZURES.
beta-amino acid;
piperidinemonocarboxylic acid;
tertiary amino compound;
thiophenes
anticonvulsant;
GABA reuptake inhibitor
tiagabine hydrochloridetiagabine hydrochloride : A hydrochloride resulting from the reaction of equimolar amounts of tiagabine and hydrogen chloride. A GABA reuptake inhibitor, it is used for the treatment of epilepsy.hydrochlorideanticonvulsant;
GABA reuptake inhibitor
n-(4,4-diphenyl-3-butenyl)nipecotic acidN-(4,4-diphenyl-3-butenyl)nipecotic acid: structure given in first sourcediarylmethane
nnc 711NNC 711: structure in first source
sk&f 100330-aSK&F 100330-A: structure given in first source
ci 966CI 966: GABA uptake blocker; RN from Toxlitdiarylmethane
hinokininhinokinin : A lignan that is dihydrofuran-2(3H)-one (gamma-butyrolactone) substituted by a 3,4-methylenedioxybenzyl group at positions 3 and 4 (the 3R,4R-diastereoisomer).

hinokinin: suppresses expression of both HBsAg and HBeAg
benzodioxoles;
gamma-lactone;
lignan
trypanocidal drug
n-(1-benzyl-4-piperidinyl)-2,4-dichlorobenzamideN-(1-benzyl-4-piperidinyl)-2,4-dichlorobenzamide: inhibits the betaine-GABA transporter 1; structure in first source
nipecotic acid(R)-nipecotic acid : The (R)-enantiopmer of nipecotic acid.amino acid zwitterion;
nipecotic acid
nipecotic acid, (s)-isomer(S)-nipecotic acid : The (S)-enantiomer of nipecotic acid.nipecotic acid
2-ethoxy-N-[1-(phenylmethyl)-4-piperidinyl]benzamidepiperidines
nnc 05-2090NNC 05-2090: structure given in first sourcecarbazoles
snap 5114