Electrogenic Properties and Substrate Specificity of the Polyspecific Rat Cation Transporter rOCT1

The previously cloned rat cation transporter rOCT1 detected in renal proximal tubules and hepatocytes (Gründemann, D., Gorboulev, V., Gambaryan, S., Veyhl, M., and Koepsell, H. (1994) Nature 372, 549-552) was expressed in Xenopus oocytes, and transport properties were analyzed using tracer uptake st...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 1996-12, Vol.271 (51), p.32599-32604
Main Authors: Busch, Andreas E., Quester, Sven, Ulzheimer, Jochen C., Waldegger, Siegfried, Gorboulev, Valentin, Arndt, Petra, Lang, Florian, Koepsell, Hermann
Format: Article
Language:English
Subjects:
Animals
Base Sequence
Biological Transport
Carrier Proteins - physiology
Cations
Choline - metabolism
Electric Conductivity
Kidney - metabolism
Lidocaine - metabolism
Membrane Potentials
Membrane Proteins - physiology
Molecular Sequence Data
Niacinamide - analogs & derivatives
Niacinamide - metabolism
Organic Cation Transporter 1
Pyridinium Compounds - metabolism
Rats
Recombinant Proteins
Substrate Specificity
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The previously cloned rat cation transporter rOCT1 detected in renal proximal tubules and hepatocytes (Gründemann, D., Gorboulev, V., Gambaryan, S., Veyhl, M., and Koepsell, H. (1994) Nature 372, 549-552) was expressed in Xenopus oocytes, and transport properties were analyzed using tracer uptake studies and electrophysiological measurements. rOCT1 induced highly active transport of a variety of cations, including the classical substrates for cation transport, such as N-1-methylnicotinamide, 1-methyl-4-phenylpyridinium (MPP), and tetraethylammonium (TEA), but also the physiologically important choline. In oocytes rOCT1 also mediated efflux of MPP, which could be trans-stimulated by MPP and TEA. Cation transport via rOCT1 was electrogenic. In voltage-clamped oocytes, transport of TEA and choline via rOCT1 produced inwardly directed currents, which were independent of extracellular ion composition or pH. The choline- and TEA-induced currents were voltage-dependent at nonsaturating concentrations, and the apparent affinity of these cations was decreased at depolarized voltages. Other substrates transported by rOCT1 were the polyamines spermine and spermidine. Interestingly, the previously described potent inhibitors of rOCT1, cyanine 863, quinine, and D-tubocurarine were substrates themselves. The data indicate that rOCT1 is an effective transport system that is responsible for electrogenic uptake of a wide variety of organic cations into epithelial cells of renal proximal tubules and hepatocytes.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.271.51.32599