The ionic stoichiometry of the GLAST glutamate transporter in salamander retinal glia.
Maintaining a low extracellular glutamate concentration in the central nervous system is important for terminating synaptic transmission and preventing excitotoxic cell death. The stoichiometry of the most abundant glutamate transporter, GLT-1, predicts that a very low glutamate concentration, approximately 2 nM, should be reached in the absence of glutamate release, yet microdialysis measurements give a value of approximately 1 microM. If other glutamate transporters had a different stoichiometry, the predicted minimum glutamate concentration could be higher, for example if those transporters were driven by the cotransport of 2 Na+ (rather than of 3 Na+ as for GLT-1). Here we investigated the ionic stoichiometry of the glutamate transporter GLAST, which is the major glutamate transporter expressed in the retina and cerebellum, is expressed in other adult brain areas at a lower level than GLT-1, and is present throughout the brain early in development when expression of GLT-1 is low. Glutamate transport by GLAST was found to be driven, as for GLT-1, by the cotransport of 3 Na+ and 1 H+ and the counter-transport of 1 K+, suggesting that the minimum extracellular glutamate concentration should be similar during development and in the adult brain. A less powerful accumulation of glutamate by GLAST than by GLT-1 cannot be used to explain the high glutamate concentration measured by microdialysis.
Owe
Simen Gylterud
SG
Department of Physiology, University College London, London, WC1E 6BT, UK.
Marcaggi
Païkan
P
Attwell
David
D
D027322:Amino Acid Transport System X-AG / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology; D003198:Computer Simulation; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D050580:Excitatory Amino Acid Transporter 3 / Q000378:metabolism; D050582:Excitatory Amino Acid Transporter 5 / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D008954:Models, Biological; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D011522:Protons; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D014562:Caudata
D027322:Amino Acid Transport System X-AG; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D050580:Excitatory Amino Acid Transporter 3; D050582:Excitatory Amino Acid Transporter 5; D011522:Protons; C120673:benzyloxyaspartate; D001224:Aspartic Acid; D018698:Glutamic Acid; D012964:Sodium; D011188:Potassium