Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 479, Issue 1-3, Pages 213-221Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2003.08.070
Keywords
DAT (dopamine transporter); dopamine recognition; cation; Na+; access model
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Funding
- NIDA NIH HHS [DA 08379, DA 13261] Funding Source: Medline
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Advances have been made in characterizing the relationship between Na+ and the substrate permeation pathway in the dopamine transporter. This review covers the role of Na+ in co-transport with dopamine as well as in the recognition of dopamine. Apparent recognition depends on the preparation studied: it differs between intact cells heterologously expressing the dopamine transporter and membranes prepared from these cells. In our search for amino acid residues in the transporter involved in Na+ action, W84 and D313 were found to play a special role in cation interaction, with evidence for regulation of both Na and H+ sensitivity. Mutation of D313 to N appeared to decrease the affinity for the dopamine transporter in intact cells, not by altering recognition per se. A model is proposed in which access of dopamine, not recognition itself is regulated by D313 and Na+. Thus, the role of external Na+ in intact cell preparations is to turn dopamine transporters to the externally facing form, allowing access of dopamine to its binding site. (C) 2003 Elsevier B.V. All rights reserved.
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