Although from outside the brain looks like a static organ, if we could see its activity we would be surprised. The millions of neurons it contains are in constant interaction, day and night. In some moments it is more active, in others less, but it never stops. Neurons interact with each other through the neuronal synapse, and one of the most important components in the synapse is neurotransmitters. Among the amount of neurotransmitters that exist, in this article we are going to address the neurotransmitter gamma-aminobutyric acid, better known as GABA.
- 1 GABA
- 2 Synthesis and storage of GABA
- 3 Inactivation
- 4 GABA receivers
- 5 GABA-ergic neurons
As the Cortés-Romero (2011) team states, "the amino acid gamma-aminobutyric acid (GABA) It is the most abundant inhibitor type chemical messenger in the central nervous system, suggesting that 30 or 40% of brain neurons use GABA as a neurotransmitter ". The presence of GABA in the nervous tissue ensures the balance between excitation and neuronal inhibition, which is a key requirement in cognitive, motor and sensory functions.
Synthesis and storage of GABA
The synthesis occurs almost entirely with glutamate as a precursor. GABA levels are maintained thanks to a cycle that consistently provides glutamate and involves glial cells and neuronal presynaptic terminals. When GABA is transported into the glial cell, it is transformed into glutamate by the action of GABA-Transaminase (GABA-T). The resulting glutamate, by the action of glutamine synthetase, is transformed into glutamine and it is exported to the neuron, where it is transformed back into glutamate by the action of glutaminase.
In the last step, thanks to the action of the above GAD (glutamic acid decarboxylase), glutamate is converted into GABA. GABA is stored in synaptic vesicles and is released thanks to the arrival of a depolarizing stimulus based on calcium concentration. GABA can be removed from the extracellular space through specific transports of the membrane. These transports are known as: GAT-1, GAT-2, GAT-3 and GAT-4.
When GABA is released into the synaptic space, the GABA-T transport protein (GABA alpha-oxoglutarate transaminase) recaptures it. A part of the recaptured GABA can be reused, but a part is inactivated by enzymatic degradation. When a molecule of GABA-T degrades one of GABA, a molecule of alpha-ketoglutarate is converted to glutamate. Thus, for each molecule of GABA that degrades, a new molecule of the glutamate precursor is produced. This process ensures that the neurotransmitter reserves are not depleted.
GABA can act on three types of receptors: GABA-A, GABA-B and GABA-C. The GABA-A and C receptors are ionotropic, while the GABA-B receptor is metabotropic.
It is an ionotropic receptor. It is coupled to a Cl- e channel hyperpolarizes the membrane. It is located in the postsynaptic membranes. GABA-B receptors are widely distributed throughout the brain and are found in both neurons and glial cells. This type of receptor causes rapid and transient responses and is part of a macromolecular group with points of attachment to other substances such as alcohol, GABA, barbiturates, benzodiazepines, neurosteroids, inhalatable anesthetics and picrotoxin.
The GABA-B receptor is metabotropic and there are two subtypes: GABA B1 and GABA B2. It is inhibitory. It inhibits the production of cAMP (cyclic adenosine monophosphate) and facilitates the opening of sodium channels. GABA-B receptors, are found especially in the cortex, the thalamus, the superior collicles, the cerebellum and in the dorsal horns of the spinal cord. Its location is both presynaptic and postsynaptic.
It is an ionotropic receptor and despite its resemblance to GABA-A, it is insensitive to benzodiazepines and barbiturates. It is coupled to a Cl- channel, so its effect is to hyperpolarize the membrane.GABA-C receptors have only been found in the pituitary and retina. Its location is in the postsynaptic membranes. These receptors cause slow and lasting responses. The abundance of this receptor in the retina has been associated with the processing of retinal signals.
GABA-ergic neurons are especially numerous in the striatum, in the pale globe, in the black substance and in the cerebellum. They are neurons immune to GABA or its GAD synthesizing enzyme. The local or long-range GABA-ergic action is inhibitory and controls the activity of the exciter systems to maintain a correct balance between excitation and neuronal inhibition.
Alterations in the development and function of the GABA-ergic system lead to a destabilization of this delicate balance, which produces neurological disorders and developmental and psychiatric disorders. Among these types of alterations can be found: epilepsy, schizophrenia, mental retardation, autism, Tourette's syndrome and anxiety.
- Cortés-Romero, C., Galindo, F., Galicia-Isasmendi, S. and Flores, A. (2011). GABA Functional duality? Transition during neurodevelopment. Journal of Neurology, 52 (11), 665-675.
- Redolar, D. (2013). Cognitive neuroscience. Madrid: Pan American Medical Editorial.
- Redolar, D. (2010). Fundamentals of psychobiology. Barcelona: UOC Publishing.