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Cystic fibrosis transmembrane conductance regulator. Physical basis for lyotropic anion selectivity patterns.

Smith SS, Steinle ED, Meyerhoff ME, Dawson DC - J. Gen. Physiol. (1999)

Bottom Line: The calculated energies of anion-channel interaction, derived from measurements of either permeability or binding, varied as a linear function of inverse ionic radius (1/r), as expected from a Born-type model of ion charging in a medium characterized by an effective dielectric constant of 19.These large anions also bind more tightly for the same reason: the reduced energy of hydration allows the net transfer energy (the well depth) to be more negative.Anions that are smaller (more difficult to dehydrate) than Cl are energetically retarded from entering the channel, while the larger (more readily dehydrated) anions are retarded in their passage by "sticking" within the channel.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, University of Michigan, Ann Arbor, Michigan 48109, USA.

ABSTRACT
The cystic fibrosis transmembrane conductance regulator (CFTR) Cl channel exhibits lyotropic anion selectivity. Anions that are more readily dehydrated than Cl exhibit permeability ratios (P(S)/P(Cl)) greater than unity and also bind more tightly in the channel. We compared the selectivity of CFTR to that of a synthetic anion-selective membrane [poly(vinyl chloride)-tridodecylmethylammonium chloride; PVC-TDMAC] for which the nature of the physical process that governs the anion-selective response is more readily apparent. The permeability and binding selectivity patterns of CFTR differed only by a multiplicative constant from that of the PVC-TDMAC membrane; and a continuum electrostatic model suggested that both patterns could be understood in terms of the differences in the relative stabilization of anions by water and the polarizable interior of the channel or synthetic membrane. The calculated energies of anion-channel interaction, derived from measurements of either permeability or binding, varied as a linear function of inverse ionic radius (1/r), as expected from a Born-type model of ion charging in a medium characterized by an effective dielectric constant of 19. The model predicts that large anions, like SCN, although they experience weaker interactions (relative to Cl) with water and also with the channel, are more permeant than Cl because anion-water energy is a steeper function of 1/r than is the anion-channel energy. These large anions also bind more tightly for the same reason: the reduced energy of hydration allows the net transfer energy (the well depth) to be more negative. This simple selectivity mechanism that governs permeability and binding acts to optimize the function of CFTR as a Cl filter. Anions that are smaller (more difficult to dehydrate) than Cl are energetically retarded from entering the channel, while the larger (more readily dehydrated) anions are retarded in their passage by "sticking" within the channel.

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The absolute value of the hydration energy (/ΔGhyd/) plotted as a function of reciprocal anion radius (or equivalent sphere radius). The filled circles represent the halides and pseudohalides (Table ), and the open circles represent the polyatomic anions, which are noted on the figure for clarity. The solid line is the best fit to the data for the halides and pseudohalides; it has a slope of 674.5, y intercept of 8.8, and a correlation coefficient of 0.94. The dotted lines are the 95% prediction intervals (confidence intervals of the population).
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Figure 1: The absolute value of the hydration energy (/ΔGhyd/) plotted as a function of reciprocal anion radius (or equivalent sphere radius). The filled circles represent the halides and pseudohalides (Table ), and the open circles represent the polyatomic anions, which are noted on the figure for clarity. The solid line is the best fit to the data for the halides and pseudohalides; it has a slope of 674.5, y intercept of 8.8, and a correlation coefficient of 0.94. The dotted lines are the 95% prediction intervals (confidence intervals of the population).

Mentions: In the Born model, the free energy of ion-solvent interaction is equated with the work required to move a charged sphere of radius, r, from a vacuum into a structureless continuum characterized by a dielectric constant, ∈ (Bockris and Reddy 1970). For each ion listed in Table , we obtained the equivalent radius from the molecular model (applying the correction of Latimer et al. 1939 (0.1 Å for anions and 0.85 Å for cations) and calculated the work of transfer from a vacuum to water (∈ = 80). There is reasonable agreement between the hydration energy calculated this way and the measured values for the halides and pseudohalides (Marcus 1997), but very poor correspondence for a number of the polyatomic anions. Gluconate, for example, is much more difficult to dehydrate than predicted by the Born analysis based on its equivalent radius, presumably due to the increased local charge density resulting from nonuniform charge distribution (Marcus 1997). This point is demonstrated in Fig. 1, which shows values of /ΔGhyd/ plotted versus reciprocal ionic radius. It is apparent that the polyatomic anions (often used for sizing anion-selective pores; Bormann et al. 1987; Halm and Frizzell 1992; Linsdell et al. 1998) exhibit thermodynamic behavior consistent with an equivalent “Born thermochemical radius” that is much smaller than any actual dimension of the molecule (Table ).


Cystic fibrosis transmembrane conductance regulator. Physical basis for lyotropic anion selectivity patterns.

Smith SS, Steinle ED, Meyerhoff ME, Dawson DC - J. Gen. Physiol. (1999)

The absolute value of the hydration energy (/ΔGhyd/) plotted as a function of reciprocal anion radius (or equivalent sphere radius). The filled circles represent the halides and pseudohalides (Table ), and the open circles represent the polyatomic anions, which are noted on the figure for clarity. The solid line is the best fit to the data for the halides and pseudohalides; it has a slope of 674.5, y intercept of 8.8, and a correlation coefficient of 0.94. The dotted lines are the 95% prediction intervals (confidence intervals of the population).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2230651&req=5

Figure 1: The absolute value of the hydration energy (/ΔGhyd/) plotted as a function of reciprocal anion radius (or equivalent sphere radius). The filled circles represent the halides and pseudohalides (Table ), and the open circles represent the polyatomic anions, which are noted on the figure for clarity. The solid line is the best fit to the data for the halides and pseudohalides; it has a slope of 674.5, y intercept of 8.8, and a correlation coefficient of 0.94. The dotted lines are the 95% prediction intervals (confidence intervals of the population).
Mentions: In the Born model, the free energy of ion-solvent interaction is equated with the work required to move a charged sphere of radius, r, from a vacuum into a structureless continuum characterized by a dielectric constant, ∈ (Bockris and Reddy 1970). For each ion listed in Table , we obtained the equivalent radius from the molecular model (applying the correction of Latimer et al. 1939 (0.1 Å for anions and 0.85 Å for cations) and calculated the work of transfer from a vacuum to water (∈ = 80). There is reasonable agreement between the hydration energy calculated this way and the measured values for the halides and pseudohalides (Marcus 1997), but very poor correspondence for a number of the polyatomic anions. Gluconate, for example, is much more difficult to dehydrate than predicted by the Born analysis based on its equivalent radius, presumably due to the increased local charge density resulting from nonuniform charge distribution (Marcus 1997). This point is demonstrated in Fig. 1, which shows values of /ΔGhyd/ plotted versus reciprocal ionic radius. It is apparent that the polyatomic anions (often used for sizing anion-selective pores; Bormann et al. 1987; Halm and Frizzell 1992; Linsdell et al. 1998) exhibit thermodynamic behavior consistent with an equivalent “Born thermochemical radius” that is much smaller than any actual dimension of the molecule (Table ).

Bottom Line: The calculated energies of anion-channel interaction, derived from measurements of either permeability or binding, varied as a linear function of inverse ionic radius (1/r), as expected from a Born-type model of ion charging in a medium characterized by an effective dielectric constant of 19.These large anions also bind more tightly for the same reason: the reduced energy of hydration allows the net transfer energy (the well depth) to be more negative.Anions that are smaller (more difficult to dehydrate) than Cl are energetically retarded from entering the channel, while the larger (more readily dehydrated) anions are retarded in their passage by "sticking" within the channel.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, University of Michigan, Ann Arbor, Michigan 48109, USA.

ABSTRACT
The cystic fibrosis transmembrane conductance regulator (CFTR) Cl channel exhibits lyotropic anion selectivity. Anions that are more readily dehydrated than Cl exhibit permeability ratios (P(S)/P(Cl)) greater than unity and also bind more tightly in the channel. We compared the selectivity of CFTR to that of a synthetic anion-selective membrane [poly(vinyl chloride)-tridodecylmethylammonium chloride; PVC-TDMAC] for which the nature of the physical process that governs the anion-selective response is more readily apparent. The permeability and binding selectivity patterns of CFTR differed only by a multiplicative constant from that of the PVC-TDMAC membrane; and a continuum electrostatic model suggested that both patterns could be understood in terms of the differences in the relative stabilization of anions by water and the polarizable interior of the channel or synthetic membrane. The calculated energies of anion-channel interaction, derived from measurements of either permeability or binding, varied as a linear function of inverse ionic radius (1/r), as expected from a Born-type model of ion charging in a medium characterized by an effective dielectric constant of 19. The model predicts that large anions, like SCN, although they experience weaker interactions (relative to Cl) with water and also with the channel, are more permeant than Cl because anion-water energy is a steeper function of 1/r than is the anion-channel energy. These large anions also bind more tightly for the same reason: the reduced energy of hydration allows the net transfer energy (the well depth) to be more negative. This simple selectivity mechanism that governs permeability and binding acts to optimize the function of CFTR as a Cl filter. Anions that are smaller (more difficult to dehydrate) than Cl are energetically retarded from entering the channel, while the larger (more readily dehydrated) anions are retarded in their passage by "sticking" within the channel.

Show MeSH
Related in: MedlinePlus