GABA and glutamate transporters: New events and function in the vertebrate retina.

Abstract

The neural retina is a highly complex tissue composed of excitatory and inhibitory neurons and glial cells. Glutamate, the main excitatory neurotransmitter, mediates information transfer from photoreceptors, bipolar cells, and ganglion cells, whereas interneurons, mainly amacrine and horizontal cells, use γ-aminobutyric acid (GABA), the main inhibitory neurotransmitter. In this review we place an emphasis on glutamate and GABA transporters as highly regulated molecules that play fundamental roles in neurotransmitter clearance, neurotransmitter release, and oxidative stress. We pharmacologically characterized glutamate transporters in chicken retina cells and identified two glutamate transporters: one Na + -dependent transporter and one Na + -independent transporter. The Na + -dependent uptake system presented characteristics related to the high-affinity x AG -system (EAAT1), and the Na + -independent uptake system presented characteristics related to the x CG -system, which highly contributes to glutamate transport in the retina. Glutamate shares the x CG -system with another amino acid, L-cysteine, suggesting the possible involvement of glutathione. Both transporter proteins are present mainly in Müller glial cells. GABA transporters (GATs) mediate high-affinity GABA uptake from the extracellular space and terminate the synaptic action of GABA in the central nervous system. GABA transporters can be modulated by molecules that act on specific sites to promote transporter phosphorylation and dephosphorylation. In addition to a role in the clearance of GABA, GATs may also release GABA through a reverse transport mechanism. In the chicken retina, a GAT-1 blocker, but not GAT2/3 blocker, was shown to inhibit GABA uptake, suggesting that GABA release from retina cells is mainly mediated by a GAT-1-like transporter.

Neuroimmunology of rabies: New insights into an ancient disease

“…On the other hand, because of the unique metabolism of the brain, in particular, that of the cortical region, which is directly linked to both GABAergic and glutamatergic synapses, high energy consumption is the direct consequence. However, GABAergic activity requires less energy catabolism than glutamatergic neurons 161 . Howarth et al 162 indicated that most energy used for excitatory signaling is related to postsynaptic glutamate NMDA and non‐NMDA receptors.…”

“…However, GABAergic activity requires less energy catabolism than glutamatergic neurons. 161 Howarth et al 162 indicated that most energy used for excitatory signaling is related to postsynaptic glutamate NMDA and non-NMDA receptors. They require energy to reverse the influx of Ca 2+ and Na 2+ ions associated with the ionotropic glutamate receptors, showing the influence of excitatory signaling on CNS metabolism homeostasis.…”

Structure, Function, and Modulation of γ-Aminobutyric Acid Transporter 1 (GAT1) in Neurological Disorders: A Pharmacoinformatic Prospective

“…Bio-physiologically, GAT1 encompass four basic properties thoroughly determined by [ 3 H] GABA uptake assays performed on rats: (i) GAT1 have strong affinity for GABA molecules as a substrate at low micromolar concentration (Guastella et al, 1990 ), (ii) the increase rate of GABA uptake in the presence of K + - selective ionophore valinomycin help in the determination of the fact that this transport is voltage dependent across the membrane (Kanner, 1978 ; D'adamo et al, 2013 ), (iii) replacement of Na + ion with other cations e.g., Li + , K + , Tris + may affect the transport mechanism thus, suggesting Na + ion crucial for the transport (Iversen and Neal, 1968 ; Nascimento et al, 2013 ), and (iv) the GABA transport requires electrochemical gradient of Na + ion which is generated by Na + /K + ATPase activity (Guastella et al, 1990 ; Hertz et al, 2013 ).…”