Linked Life Data

15878879

Source:http://linkedlifedata.com/resource/pubmed/id/15878879

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
26
pubmed:dateCreated
2005-6-27
pubmed:abstractText
Organic cation transporters of the OCT family mediate downhill transport of organic cations, compatible with carrier, pore, or gate-lumen-gate mechanisms. We studied rat OCT2 expressed in Xenopus oocytes by the two-electrode voltage-clamp technique, including membrane capacitance (C(m)) monitoring. Choline, a transported cationic substrate, elicited the expected inward currents but also elicited decreases of C(m). Similar C(m) decreases were caused by the non-transported inhibitors tetrabutylammonium (a cation) and corticosterone (uncharged). Effects on C(m) were voltage-dependent, with a maximum at -140 mV. These findings suggest that the empty rOCT2 protein can undergo an electrogenic conformation change, with one conformation highly favored at physiological voltage. Moreover, alkali cations elicited considerable inward currents and inhibited uptake of [(14)C]tetraethylammonium with a sequence Cs(+) > Rb(+) > K(+) > Na(+) approximately Li(+). Cs(+) affected current and capacitance with similar affinity (K(0.5) approximately 50 mm). Tetraethylammonium inhibited Cs(+) currents in a concentration-dependent manner. Conversely, Cs(+) inhibited tetraethylammonium uptake by a competitive mechanism. Activation energy of the currents estimated from measurements between 12 degrees C and 32 degrees C was approximately 81 kJ/mol for Cs(+) and 39 kJ/mol for tetramethylammonium, compatible with permeation of Cs(+) through rOCT2 along the same path as organic substrates and by a mechanism different from simple electrodiffusion. Rationalization of Cs(+) selectivity in terms of a pore pointed to a pore diameter of approximately 4 A. Intriguingly, that value matches the known selectivity of rOCT2 for organic compounds. Our data show that selective permeability of rOCT2 is not determined by ligand affinity but might rather be understood in terms of the ion channel concept of a distinct "selectivity filter."
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
280
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
24481-90
pubmed:meshHeading
pubmed-meshheading:15878879-Adrenal Cortex Hormones, pubmed-meshheading:15878879-Animals, pubmed-meshheading:15878879-Biological Transport, pubmed-meshheading:15878879-Calcium, pubmed-meshheading:15878879-Cations, pubmed-meshheading:15878879-Cesium, pubmed-meshheading:15878879-Choline, pubmed-meshheading:15878879-Diffusion, pubmed-meshheading:15878879-Dose-Response Relationship, Drug, pubmed-meshheading:15878879-Electrophysiology, pubmed-meshheading:15878879-Ions, pubmed-meshheading:15878879-Ligands, pubmed-meshheading:15878879-Membrane Transport Proteins, pubmed-meshheading:15878879-Models, Biological, pubmed-meshheading:15878879-Oocytes, pubmed-meshheading:15878879-Organic Cation Transport Proteins, pubmed-meshheading:15878879-Patch-Clamp Techniques, pubmed-meshheading:15878879-Protein Binding, pubmed-meshheading:15878879-Rats, pubmed-meshheading:15878879-Temperature, pubmed-meshheading:15878879-Tetraethylammonium, pubmed-meshheading:15878879-Time Factors, pubmed-meshheading:15878879-Xenopus laevis
pubmed:year
2005
pubmed:articleTitle
Alkali cation binding and permeation in the rat organic cation transporter rOCT2.
pubmed:affiliation
Department of Anatomy and Cell Biology, University of Würzburg, Koellikerstrasse 6, 97070 Würzburg, Germany. bernhard.schmitt@mail.uni-wuerzburg.de
pubmed:publicationType
Journal Article