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D-Enantiomers Take a Close Look at the Functioning of a Cardiac Cationic L-Amino Acid Transporter
- Source :
- Biophysical Journal. 99(10):3224-3233
- Publication Year :
- 2010
- Publisher :
- Elsevier BV, 2010.
-
Abstract
- Cationic amino acid transporters are highly selective for L-enantiomers such as L-arginine (L-Arg). Because of this stereoselectivity, little is known about the interaction of these transporters with D-isomers. To study whether these compounds can provide information on the molecular mechanism of transport, inward currents activated by L-Arg with low apparent affinity were measured in whole-cell voltage-clamped cardiomyocytes as a function of extracellular L-Arg and D-Arg concentrations. D-Arg inhibited L-Arg currents in a membrane-potential (VM)-dependent competitive manner, indicating the presence of D-Arg binding sites in the carrier. Analysis of these steady-state currents showed that L- and D-Arg binding reactions dissipate a similar small fraction of the membrane electric field. Since D-Arg is not transported, these results suggest that enantiomer recognition occurs at conformational transitions that initiate amino acid translocation. The VM dependence of maximal current levels suggests that inward currents arise from the slow outward movement of negative charges in the unliganded transporter. Translocation of the L-Arg-bound complex, on the other hand, appears to be electroneutral. D-Arg-dependent transient charge movements, also detected in these cells, displayed a VM-dependent charge distribution and kinetics that are consistent with amino acid binding in an ion well in a shallow, water-filled extracellular binding pocket.
- Subjects :
- Male
Patch-Clamp Techniques
Arginine
Stereochemistry
Molecular Sequence Data
Biophysics
Models, Biological
03 medical and health sciences
0302 clinical medicine
Extracellular
Animals
Humans
Myocytes, Cardiac
Amino Acid Sequence
Channels and Transporters
Patch clamp
Amino acid transporter
Binding site
030304 developmental biology
chemistry.chemical_classification
0303 health sciences
Myocardium
Stereoisomerism
Transporter
Rats
Amino acid
Kinetics
chemistry
Amino Acid Transport Systems, Basic
Amino acid binding
Ion Channel Gating
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 00063495
- Volume :
- 99
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Biophysical Journal
- Accession number :
- edsair.doi.dedup.....fa50aae1b7811ee59a0a61ec8d899d75
- Full Text :
- https://doi.org/10.1016/j.bpj.2010.09.025