title: Mechanism of electrogenic cation transport by the cloned organic cation transporter 2 from rat.
abstract: The organic cation transporter 2 (OCT2) is expressed in plasma membranes of kidney and brain. Its transport mechanism and substrates are debated. We studied substrate-induced changes of electrical current with the patch clamp technique after expression of rat OCT2 in oocytes. Activation of current, corresponding to efflux, was observed for small organic cations, e.g. choline. In contrast, the bigger cations quinine and tetrabutylammonium elicited no change in current. However, transport of choline could be inhibited by applying quinine or tetrabutylammonium to the cytoplasmic side. Inhibition of organic cation efflux by quinine was competitive with substrates. Quinine at the inside also inhibited substrate influx from the outside. Current-voltage analysis showed that both maximal turnover and apparent affinity to substrates are voltage-dependent. Substrate-induced currents with organic cations on both membrane sides reversed as predicted from the Nernst potential. Our results clearly identify the electrochemical potential as driving force for transport at neutral pH and exclude an electroneutral H(+)/organic cation(+) exchange. We suggest the existence of an electroneutral organic cation(+) exchange and propose a model for a carrier-type transport mechanism.
authors.affiliation: Max-Planck-Institute for Biophysics, Kennedyallee 70, D-60596 Frankfurt/M, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Budiman
authors.forename: E
authors.initials: E
authors.lastname: Bamberg
authors.forename: H
authors.initials: H
authors.lastname: Koepsell
authors.forename: G
authors.initials: G
authors.lastname: Nagel
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D002412:Cations; D003001:Cloning, Molecular; D004594:Electrophysiology; D017136:Ion Transport / Q000502:physiology; D027701:Organic Cation Transport Proteins; D000075102:Organic Cation Transporter 2; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D002412:Cations; D027701:Organic Cation Transport Proteins; D000075102:Organic Cation Transporter 2; D011994:Recombinant Proteins; C100590:Slc22a2 protein, rat