title: Electrogenic properties and substrate specificity of the polyspecific rat cation transporter rOCT1.
abstract: 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.
authors.affiliation: Institut für Physiologie der Eberhard-Karls-Universität, 72076 Tübingen, Germany. andreas.busch@uni-tuebingen.de
authors.forename: A E
authors.initials: AE
authors.lastname: Busch
authors.forename: S
authors.initials: S
authors.lastname: Quester
authors.forename: J C
authors.initials: JC
authors.lastname: Ulzheimer
authors.forename: S
authors.initials: S
authors.lastname: Waldegger
authors.forename: V
authors.initials: V
authors.lastname: Gorboulev
authors.forename: P
authors.initials: P
authors.lastname: Arndt
authors.forename: F
authors.initials: F
authors.lastname: Lang
authors.forename: H
authors.initials: H
authors.lastname: Koepsell
mesh_terms: D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D002352:Carrier Proteins / Q000502:physiology*; D002412:Cations; D002794:Choline / Q000378:metabolism*; D004553:Electric Conductivity; D007668:Kidney / Q000378:metabolism*; D008012:Lidocaine / Q000378:metabolism; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000502:physiology*; D008969:Molecular Sequence Data; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000378:metabolism; D027702:Organic Cation Transporter 1; D011726:Pyridinium Compounds / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins; D013379:Substrate Specificity
chemical_list: D002352:Carrier Proteins; D002412:Cations; D008565:Membrane Proteins; D027702:Organic Cation Transporter 1; D011726:Pyridinium Compounds; D011994:Recombinant Proteins; D009536:Niacinamide; C026560:1-(4-methoxyphenyl)pyridinium; D008012:Lidocaine; D002794:Choline; C008472:N-methylnicotinamide