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Eur J Pharmacol. 2003 Oct 31;479(1-3):213-21.

Na+ and the substrate permeation pathway in dopamine transporters.

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  • 1Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine, Box 1649, Peoria, IL 61656-1649, USA.


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.

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