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Extracellular charge adsorption influences intracellular electrochemical homeostasis in amphibian skeletal muscle.

Mehta AR, Huang CL, Skepper JN, Fraser JA - Biophys. J. (2008)

Bottom Line: The membrane potential measured by intracellular electrodes, E(m), is the sum of the transmembrane potential difference (E(1)) between inner and outer cell membrane surfaces and a smaller potential difference (E(2)) between a volume containing fixed charges on or near the outer membrane surface and the bulk extracellular space.First, analytic equations were developed to calculate the influence of charges constrained within a three-dimensional glycocalyceal matrix enveloping the cell membrane outer surface upon local electrical potentials and ion concentrations.Electron microscopy confirmed predictions of these equations that extracellular charge adsorption influences glycocalyceal volume.

View Article: PubMed Central - PubMed

Affiliation: Physiological Laboratory, University of Cambridge, Cambridge, United Kingdom.

ABSTRACT
The membrane potential measured by intracellular electrodes, E(m), is the sum of the transmembrane potential difference (E(1)) between inner and outer cell membrane surfaces and a smaller potential difference (E(2)) between a volume containing fixed charges on or near the outer membrane surface and the bulk extracellular space. This study investigates the influence of E(2) upon transmembrane ion fluxes, and hence cellular electrochemical homeostasis, using an integrative approach that combines computational and experimental methods. First, analytic equations were developed to calculate the influence of charges constrained within a three-dimensional glycocalyceal matrix enveloping the cell membrane outer surface upon local electrical potentials and ion concentrations. Electron microscopy confirmed predictions of these equations that extracellular charge adsorption influences glycocalyceal volume. Second, the novel analytic glycocalyx formulation was incorporated into the charge-difference cellular model of Fraser and Huang to simulate the influence of extracellular fixed charges upon intracellular ionic homeostasis. Experimental measurements of E(m) supported the resulting predictions that an increased magnitude of extracellular fixed charge increases net transmembrane ionic leak currents, resulting in either a compensatory increase in Na(+)/K(+)-ATPase activity, or, in cells with reduced Na(+)/K(+)-ATPase activity, a partial dissipation of transmembrane ionic gradients and depolarization of E(m).

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The influence of zX(g) upon [X]g and Σg at varying η according to Gibbs-Donnan theory. Equation 12 was used to predict the relationship between [X]g (A) or Σg (B) and zX(g) at different values of η. In both panels, the isobars show values of η from 1.01 (lines closest to the x axis) to 1.1 (lines furthest from the x axis) at intervals of 0.01. Note that η = 1 gives [X]g = 0 at any value of zX(g). As demonstrated in A, increases in the magnitude of zX(g) reduce the steady-state value of [X]g for any value of η other than 1. As total glycocalyx Xg content is fixed by definition, this implies that increases in the magnitude of zX(g) produce swelling of the glycocalyx. Furthermore, as the steady-state fixed charge density of the glycocalyx ([Σ]g, in giga-Coulombs/l, or, equivalently, C nl−1) is given by the product FzX(g)[X]g (Eq. 9), such volume changes dampen the influence of zX(g) upon [Σ]g (B), thereby limiting the range of values that [Σ]g may take according to the value of η.
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fig4: The influence of zX(g) upon [X]g and Σg at varying η according to Gibbs-Donnan theory. Equation 12 was used to predict the relationship between [X]g (A) or Σg (B) and zX(g) at different values of η. In both panels, the isobars show values of η from 1.01 (lines closest to the x axis) to 1.1 (lines furthest from the x axis) at intervals of 0.01. Note that η = 1 gives [X]g = 0 at any value of zX(g). As demonstrated in A, increases in the magnitude of zX(g) reduce the steady-state value of [X]g for any value of η other than 1. As total glycocalyx Xg content is fixed by definition, this implies that increases in the magnitude of zX(g) produce swelling of the glycocalyx. Furthermore, as the steady-state fixed charge density of the glycocalyx ([Σ]g, in giga-Coulombs/l, or, equivalently, C nl−1) is given by the product FzX(g)[X]g (Eq. 9), such volume changes dampen the influence of zX(g) upon [Σ]g (B), thereby limiting the range of values that [Σ]g may take according to the value of η.

Mentions: From a theoretical standpoint (Eq. 12), the two variables that would be expected to influence [X]g, and consequently glycocalyceal volume at constant extracellular osmolarity, are zX(g) and η (the mean charge valency of Xg per osmole and the permitted ratio between total ion concentrations in the glycocalyx relative to the bulk extracellular solutions, respectively). Thus, Fig. 4 demonstrates the influences of zX(g) and η upon [X]g (Fig. 4 A) and the resultant value of [Σ]g (Fig. 4 B), the latter being the product FzX(g)[X]g. This demonstrates that higher magnitudes of zX(g) result in reduced steady-state [X]g (Fig. 4 A), hence constraining [Σ]g within limits primarily determined by η (Fig. 4 B). Since, by definition, the glycocalyx contains a fixed quantity of Xg, such reductions in steady-state [X]g predict that increases in the magnitude of zX(g) would increase glycocalyceal volume from a minimum volume when zX(g) = 0.


Extracellular charge adsorption influences intracellular electrochemical homeostasis in amphibian skeletal muscle.

Mehta AR, Huang CL, Skepper JN, Fraser JA - Biophys. J. (2008)

The influence of zX(g) upon [X]g and Σg at varying η according to Gibbs-Donnan theory. Equation 12 was used to predict the relationship between [X]g (A) or Σg (B) and zX(g) at different values of η. In both panels, the isobars show values of η from 1.01 (lines closest to the x axis) to 1.1 (lines furthest from the x axis) at intervals of 0.01. Note that η = 1 gives [X]g = 0 at any value of zX(g). As demonstrated in A, increases in the magnitude of zX(g) reduce the steady-state value of [X]g for any value of η other than 1. As total glycocalyx Xg content is fixed by definition, this implies that increases in the magnitude of zX(g) produce swelling of the glycocalyx. Furthermore, as the steady-state fixed charge density of the glycocalyx ([Σ]g, in giga-Coulombs/l, or, equivalently, C nl−1) is given by the product FzX(g)[X]g (Eq. 9), such volume changes dampen the influence of zX(g) upon [Σ]g (B), thereby limiting the range of values that [Σ]g may take according to the value of η.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2480687&req=5

fig4: The influence of zX(g) upon [X]g and Σg at varying η according to Gibbs-Donnan theory. Equation 12 was used to predict the relationship between [X]g (A) or Σg (B) and zX(g) at different values of η. In both panels, the isobars show values of η from 1.01 (lines closest to the x axis) to 1.1 (lines furthest from the x axis) at intervals of 0.01. Note that η = 1 gives [X]g = 0 at any value of zX(g). As demonstrated in A, increases in the magnitude of zX(g) reduce the steady-state value of [X]g for any value of η other than 1. As total glycocalyx Xg content is fixed by definition, this implies that increases in the magnitude of zX(g) produce swelling of the glycocalyx. Furthermore, as the steady-state fixed charge density of the glycocalyx ([Σ]g, in giga-Coulombs/l, or, equivalently, C nl−1) is given by the product FzX(g)[X]g (Eq. 9), such volume changes dampen the influence of zX(g) upon [Σ]g (B), thereby limiting the range of values that [Σ]g may take according to the value of η.
Mentions: From a theoretical standpoint (Eq. 12), the two variables that would be expected to influence [X]g, and consequently glycocalyceal volume at constant extracellular osmolarity, are zX(g) and η (the mean charge valency of Xg per osmole and the permitted ratio between total ion concentrations in the glycocalyx relative to the bulk extracellular solutions, respectively). Thus, Fig. 4 demonstrates the influences of zX(g) and η upon [X]g (Fig. 4 A) and the resultant value of [Σ]g (Fig. 4 B), the latter being the product FzX(g)[X]g. This demonstrates that higher magnitudes of zX(g) result in reduced steady-state [X]g (Fig. 4 A), hence constraining [Σ]g within limits primarily determined by η (Fig. 4 B). Since, by definition, the glycocalyx contains a fixed quantity of Xg, such reductions in steady-state [X]g predict that increases in the magnitude of zX(g) would increase glycocalyceal volume from a minimum volume when zX(g) = 0.

Bottom Line: The membrane potential measured by intracellular electrodes, E(m), is the sum of the transmembrane potential difference (E(1)) between inner and outer cell membrane surfaces and a smaller potential difference (E(2)) between a volume containing fixed charges on or near the outer membrane surface and the bulk extracellular space.First, analytic equations were developed to calculate the influence of charges constrained within a three-dimensional glycocalyceal matrix enveloping the cell membrane outer surface upon local electrical potentials and ion concentrations.Electron microscopy confirmed predictions of these equations that extracellular charge adsorption influences glycocalyceal volume.

View Article: PubMed Central - PubMed

Affiliation: Physiological Laboratory, University of Cambridge, Cambridge, United Kingdom.

ABSTRACT
The membrane potential measured by intracellular electrodes, E(m), is the sum of the transmembrane potential difference (E(1)) between inner and outer cell membrane surfaces and a smaller potential difference (E(2)) between a volume containing fixed charges on or near the outer membrane surface and the bulk extracellular space. This study investigates the influence of E(2) upon transmembrane ion fluxes, and hence cellular electrochemical homeostasis, using an integrative approach that combines computational and experimental methods. First, analytic equations were developed to calculate the influence of charges constrained within a three-dimensional glycocalyceal matrix enveloping the cell membrane outer surface upon local electrical potentials and ion concentrations. Electron microscopy confirmed predictions of these equations that extracellular charge adsorption influences glycocalyceal volume. Second, the novel analytic glycocalyx formulation was incorporated into the charge-difference cellular model of Fraser and Huang to simulate the influence of extracellular fixed charges upon intracellular ionic homeostasis. Experimental measurements of E(m) supported the resulting predictions that an increased magnitude of extracellular fixed charge increases net transmembrane ionic leak currents, resulting in either a compensatory increase in Na(+)/K(+)-ATPase activity, or, in cells with reduced Na(+)/K(+)-ATPase activity, a partial dissipation of transmembrane ionic gradients and depolarization of E(m).

Show MeSH
Related in: MedlinePlus