Structure, function, and plasticity of GABA transporters

Abstract

GABA transporters belong to a large family of neurotransmitter:sodium symporters. They are widely expressed throughout the brain, with different levels of expression in different brain regions. GABA transporters are present in neurons and in astrocytes and their activity is crucial to regulate the extracellular concentration of GABA under basal conditions and during ongoing synaptic events. Numerous efforts have been devoted to determine the structural and functional properties of GABA transporters. There is also evidence that the expression of GABA transporters on the cell membrane and their lateral mobility can be modulated by different intracellular signaling cascades. The strength of individual synaptic contacts and the activity of entire neuronal networks may be finely tuned by altering the density, distribution and diffusion rate of GABA transporters within the cell membrane. These findings are intriguing because they suggest the existence of complex regulatory systems that control the plasticity of GABAergic transmission in the brain. Here we review the current knowledge on the structural and functional properties of GABA transporters and highlight the molecular mechanisms that alter the expression and mobility of GABA transporters at central synapses.

Chronic Cerebral Hypoperfusion Induced Synaptic Proteome Changes in the rat Cerebral Cortex

“…immunoreactivity is mainly present in axon terminals of symmetrical synapses in the cortex, suited for GABA recycling in the presynaptic terminals following a release event, which is essential to sustain GABAergic synaptic transmission (Scimemi, 2014). Metabotropic GABA receptors are coupled to second-messenger systems through G-proteins and mediate slow and prolonged inhibitory effects (Misgeld et al, 1995).…”

El papel del ácido gamma-aminobutírico en la depresión de la mujer

“…Los transportadores del GABA, que se encuentran distribuidos por diferentes lugares del SNC (Tabla 1), se encargan de recaptar el GABA extracelular desde las terminales presinápticas, ya que este neurotransmisor no está sujeto a degradación enzimática 11 . El GABA que es captado por los astrocitos no se utiliza de primera instancia, ya que es metabolizado a semialdehído succínico (SSA) por la GABA-transaminasa.…”

“…El glutamato, en los astrocitos, se transforma en glutamina por la glutamina sintetasa para posteriormente ser transportado a los axones terminales. En las terminaciones nerviosas, la glutamina es convertida en glutamato por la enzima glutaminasa; posteriormente, la GAD transforma el glutamato en GABA [10][11][12] . El GABA es captado por los transportadores neuronales para liberarse, ya que las terminaciones nerviosas contienen GAD o en ellas se encuentran los transportadores para la recaptura del GABA hacia las vesículas sinápticas 13 ( Fig.…”

Epigenetic Regulations of GABAergic Neurotransmission: Relevance for Neurological Disorders and Epigenetic Therapy

“…GATs, located in pre- and postsynaptic terminals, then terminate phasic GABAergic neurotransmission and also recycle GABA for reuse (fig. 1a) [12]. …”