| Electrogenic properties of the cloned Na+/glucose cotransporter: II. A transport model under nonrapid equilibrium conditions. | |
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MedLine Citation:
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PMID: 1294062 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The results of the accompanying electrophysiological study of the cloned Na+/glucose cotransporter from small intestine (Parent, L., Supplisson, S., Loo, D.D.F., Wright, E.M. (1992) J. Mémbrane Biol. 125:49-62) were evaluated in terms of a kinetic model. The steady-state and presteady-state cotransporter properties are described by a 6-state ordered kinetic model ("mirror" symmetry) with a Na+:alpha MDG stoichiometry of 2. Carrier translocation in the membrane as well as Na+ and sugar binding and dissociation are treated as a function of their individual rate constants. Empty carrier translocation and Na+ binding/dissociation are the only steps considered to be voltage dependent. Currents were associated with the translocation of the negatively charged carrier in the membrane. Negative membrane potential facilitates sugar transport. One numerical solution was found for the 14 rate constants that account quantitatively for our experiment observations: i.e., (i) sigmoidal shape of the sugar-specific current-voltage curves (absence of outward currents and inward current saturation at high negative potentials), (ii) Na+ and voltage dependence of Ksugar0.5 and isugarmax, (iii) sugar and voltage dependence of KNa0.5 and iNamax, (iv) presteady-state currents and their dependence on external Na+, alpha MDG and membrane potential, and (v) and carrier Na+ leak current. We conclude that the main voltage effect is on carrier translocation. Na+ ions that migrate from the extracellular medium to their binding sites sense 25 to 35% of the transmembrane voltage, whereas charges associated with the carrier translocation experiences 60 to 75% of the membrane electrical field. Internal Na+ ion binding is not voltage dependent. In our nonrapid equilibrium model, the rate-limiting step for sugar transport is a function of the membrane potential, [Na]o and [alpha MDG]o. At 0 mV and at saturating [Na]o and [alpha MDG]o, the rate-limiting step for sugar transport is the empty carrier translocation (5 sec-1). As the membrane potential is made more negative, the empty carrier translocation gets faster and the internal Na+ dissociation becomes increasingly rate limiting. However, as [Na]o is decreased to less than 10 mM, the rate-limiting step is the external Na+ ions binding in the 0 to -150 mV potential range. At 0 mV, the external Na+ dissociation constant KNa' is 80 mM and decreases to 24 mM at -150 mV. The external sugar dissociation constant KNaS' is estimated to be 200 microM and voltage independent. Finally, the internal leak pathway (CNa2 translocation) is insignificant.(ABSTRACT TRUNCATED AT 400 WORDS) |
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Authors:
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L Parent; S Supplisson; D D Loo; E M Wright |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The Journal of membrane biology Volume: 125 ISSN: 0022-2631 ISO Abbreviation: J. Membr. Biol. Publication Date: 1992 Jan |
Date Detail:
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Created Date: 1992-04-09 Completed Date: 1992-04-09 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0211301 Medline TA: J Membr Biol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 63-79 Citation Subset: IM |
Affiliation:
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Department of Physiology, University of California, Los Angeles School of Medicine 90024-1751. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Binding Sites Biological Transport, Active Cloning, Molecular Electric Conductivity Glucose / metabolism* Kinetics Mathematics Membrane Potentials / physiology Models, Biological* Monosaccharide Transport Proteins / genetics, metabolism* Sodium / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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DK 19567/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Monosaccharide Transport Proteins; 50-99-7/Glucose; 7440-23-5/Sodium |
| Comments/Corrections | |
Erratum In:
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J Membr Biol 1992 Nov;130(2):203 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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