| Transport Numbers in Transdermal Iontophoresis Biophysical Journal, Volume 90, Issue 8, 15 April 2006, Pages 2822-2830 Blaise Mudry, Richard H. Guy and M. Begoña Delgado-Charro Abstract Parameters determining ionic transport numbers in transdermal iontophoresis have been characterized. The transport number of an ion (its ability to carry charge) is key to its iontophoretic delivery or extraction across the skin. Using small inorganic ions, the roles of molar fraction and mobility of the co- and counterions present have been demonstrated. A direct, constant current was applied across mammalian skin in vitro. Cations were anodally delivered from either simple MCl solutions (single-ion case, M=sodium, lithium, ammonium, potassium), or binary and quaternary mixtures thereof. Transport numbers were deduced from ion fluxes. In the single-ion case, maximum cationic fluxes directly related to the corresponding ionic aqueous mobilities were found. Addition of co-ions decreased the transport numbers of all cations relative to the single-ion case, the degree of effect depending upon the molar fraction and mobility of the species involved. With chloride as the principal counterion competing to carry current across the skin (the in vivo situation), a maximum limit on the single or collective cation transport number was 0.6–0.8. Overall, these results demonstrate how current flowing across the skin during transdermal iontophoresis is distributed between competing ions, and establish simple rules with which to optimize transdermal iontophoretic transport. Abstract | Full Text | PDF (142 kb) |
| Ionic Currents in the Human Serotonin Transporter Reveal Inconsistencies in the Alternating Access Hypothesis Biophysical Journal, Volume 85, Issue 3, 1 September 2003, Pages 1548-1559 Scott V. Adams and Louis J. DeFelice Abstract We have investigated the conduction states of human serotonin transporter (hSERT) using the voltage clamp, cut-open frog oocyte method under different internal and external ionic conditions. Our data indicate discrepancies in the alternating access model of cotransport, which cannot consistently explain substrate transport and electrophysiological data. We are able simultaneously to isolate distinct external and internal binding sites for substrate, which exert different effects upon currents conducted by hSERT, in contradiction to the alternating access model. External binding sites of coupled Na ions are likewise simultaneously accessible from the internal and external face. Although Na and Cl are putatively cotransported, they have opposite effects on the internal face of the transporter. Finally, the internal K ion does not compete with internal 5-hydroxytryptamine for empty transporters. These data can be explained more readily in the language of ion channels, rather than carrier models distinguished by alternating access mechanisms: in a channel model of coupled transport, the currents represent different states of the same permeation path through hSERT and coupling occurs in a common pore. Abstract | Full Text | PDF (247 kb) |
| Anomalous Mole Fraction Effect, Electrostatics, and Binding in Ionic Channels Biophysical Journal, Volume 74, Issue 5, 1 May 1998, Pages 2327-2334 Wolfgang Nonner, Duan P. Chen and Bob Eisenberg Abstract Ionic channels bathed in mixed solutions of two permeant electrolytes often conduct less current than channels bathed in pure solutions of either. For many years, this anomalous mole fraction effect (AMFE) has been thought to occur only in single-file pores containing two or more ions at a time. Most thinking about channels incorporates this view. We show here that the AMFE arises naturally, as an electrostatic consequence of localized ion specific binding, if the average current through a channel is described by a theory (Poisson-Nernst-Planck, PNP) that computes the average electric field from the average concentration of charges in and near the channel. The theory contains only those ion-ion interactions mediated by the mean field, and it does not enforce single filing. The AMFE is predicted by PNP over a wide range of mean concentrations of ions in the channel; for example, it is predicted when (on the average) less, or much less, than one ion is found in the channel’s pore. In this treatment, the AMFE arises, in large measure, from a depletion layer produced near a region of ion-specific binding. The small excess concentration of ions in the binding region repels all nearby ions of like charge, thereby creating a depletion layer. The overall conductance of the channel arises in effect from resistors in series, one from the binding region, one from the depletion zone, and one from the unbinding region. The highest value resistor (which occurs in the depletion zone) limits the overall series conductance. Here the AMFE is not the result of single filing or multiple occupancy, and so previous views of permeation need to be revised: the presence of an AMFE does not imply that ions permeate single file through a multiply occupied pore. Abstract | Full Text | PDF (280 kb) |
Copyright © 1964 The Biophysical Society. All rights reserved.
Biophysical Journal, Volume 4, Issue 6, 421-440, 1 November 1964
doi:10.1016/S0006-3495(64)86793-X
Articles
Alan Finkelstein
The central purpose of this paper is to elucidate in a well defined system the meaning of certain phenomena and concepts associated with the active transport of ions. To this end a specific model for a carrier system which actively transports a single ionic species is analyzed and discussed in detail. It is assumed in this model that the carrier-mediated ionic transport occurs in regions of the membrane physically separate from those regions in which free ionic movement takes place,—coupling between the active and passive regions of the membrane occurring through local current flows. The model is seen to display the following characteristics: (a) Starting from identical solutions on the two sides of the membrane, there is produced a redistribution of ions; (b) with identical solutions on the two sides of the membrane there exists a potential difference across the membrane, i.e., the “pump” is electrogenic; (c) the “short circuit” current for symmetrical solutions is equal to the flux of the neutral ion carrier complex; (d) the rate of active transport (and hence of metabolism) is dependent on the ionic concentrations in the surrounding solutions. Throughout the paper comparison is made between features of the model and properties displayed by biological active transport systems, but there is no claim of an identity between the two.