Na+ and the substrate permeation pathway in dopamine transporters.
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.
Chen
Nianhang
N
Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine, Box 1649, Peoria, IL 61656-1649, USA.
Reith
Maarten E A
ME
D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D001667:Binding, Competitive; D002414:Cations, Monovalent; D050483:Dopamine Plasma Membrane Transport Proteins; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010539:Permeability / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D012964:Sodium / Q000378:metabolism* / Q000502:physiology*
D002414:Cations, Monovalent; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012964:Sodium