High-affinity glutamate transporters in the rat retina: a major role of the glial glutamate transporter GLAST-1 in transmitter clearance

• Published in: Cell and tissue research Vol. 291; no. 1; pp. 19 - 31
• Main Authors: Rauen, T, Taylor, W R, Kuhlbrodt, K, Wiessner, M
• Format: Journal Article
• Language: English
• Published: Germany 01.01.1998
• Subjects: Amino Acid Transport System X-AG; Animals; ATP-Binding Cassette Transporters - analysis; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - metabolism; Biological Transport - physiology; Carrier Proteins - analysis; Carrier Proteins - genetics; Carrier Proteins - metabolism; Excitatory Amino Acid Transporter 1; Female; Gene Expression - physiology; Glutamate Plasma Membrane Transport Proteins; Glutamic Acid - pharmacokinetics; Immunohistochemistry; Male; Neuroglia - chemistry; Neurotransmitter Agents - metabolism; Polymerase Chain Reaction; Rats; Rats, Wistar; Retina - chemistry; Retina - cytology; RNA, Messenger - analysis; Symporters; Synaptic Vesicles - chemistry; Synaptic Vesicles - metabolism; Tritium
• ISSN: 0302-766X; 1432-0878

Glutamate is the major excitatory neurotransmitter of the mammalian retina and glutamate uptake is essential for normal transmission at glutamatergic synapses. The reverse transcriptase-polymerase chain reaction (RT-PCR) has revealed the presence of three different high-affinity glutamate transporters in the rat retina, viz. GLAST-1, GLT-1 and EAAC-1. No message has been found in the retina for EAAT-4, a transporter recently cloned from human brain. By using membrane vesicle preparations of total rat retina, we show that glutamate uptake in the retina is a high-affinity electrogenic sodium-dependent transport process driven by the transmembrane sodium ion gradient. Autoradiography of intact and dissociated rat retinae indicates that glutamate uptake by Müller glial cells dominates total retinal glutamate transport and that this uptake is strongly influenced by the activity of glutamine synthetase. RT-PCR, immunoblotting and immunohistochemistry have revealed that Müller cells express only GLAST-1. The Km for glutamate of GLAST-1 is 2.1+/-0.4 microM. This study suggests a major role for the Müller cell glutamate transporter GLAST-1 in retinal transmitter clearance. By regulating the extracellular glutamate concentration, the action of GLAST-1 in Müller cells may extend beyond the protection of neurons from excitotoxicity; we suggest a mechanism by which Müller cell glutamate transport might play an active role in shaping the time course of excitatory transmission in the retina.