Localization and function of GABA transporter 1 in the retina

Abstract

Plasma membrane transporters, located in the presynaptic terminal and/or surrounding glial cells, terminate synaptic transmission by operating rapid, high affinity uptake of the neurotransmitter from the synaptic cleft. Pharmacological blockade of transporters increases extracellular neurotransmitter levels and prolongs transmitter exposure to the receptors. GABA transporters (GATs) belong to the Na+ and Cl--dependent transporter family. Four GATs have been isolated and cloned in mammals. Of them, GAT-1 and GAT-3 are expressed in the retina. GAT-1 has a widespread distribution to different retinal cell types, but it is prominently expressed in amacrine cells of all vertebrate species studied to date. There are some species differences in the expression patterns of GAT-1 in the retina. It is expressed by horizontal cells in non-mammalian but not in mammalian retinas, and it is expressed in Müller glial cells of rats and guinea pigs, but not of rabbits and primates. Functionally, GAT-1, together with GAT-3, regulates the extracellular GABA levels in the retina, thereby determining the level of inhibitory interactions and affecting visual processing in the retinal pathways. GAT-1 may interact with GABAC receptors on bipolar cell terminals and influence ganglion cell responses. It may also interact with GABAB receptors in the regulation of retinal waves of spontaneous activity which are known to play critical roles during development of the visual system. Other important functional actions are exerted by GAT-1 through reversed GABA transport. These include GABA release by cholinergic/GABAergic starburst amacrine cells and GABA release during early retinal development.