In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 98, No. 26 ( 2001-12-18), p. 15324-15329
Abstract:
Excitatory amino acid transporters (EAATs) buffer and remove
synaptically released l -glutamate and maintain its
concentrations below neurotoxic levels. EAATs also mediate a thermodynamically uncoupled substrate-gated anion conductance that may
modulate cell excitability. Here, we demonstrate that modification of a cysteine substituted within a C-terminal domain of EAAT1 abolishes
transport in both the forward and reverse directions without affecting activation of the anion conductance. EC 50 s for l -glutamate and sodium are significantly lower after
modification, consistent with kinetic models of the transport cycle that link anion channel gating to an early step in substrate
translocation. Also, decreasing the pH from 7.5 to 6.5 decreases the EC 50 for l -glutamate to activate the anion
conductance, without affecting the EC 50 for the entire
transport cycle. These findings demonstrate for the first time a structural separation of transport and the uncoupled anion flux.
Moreover, they shed light on some controversial aspects of the EAAT transport cycle, including the kinetics of proton binding and anion
conductance activation.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.011400198
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2001
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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