The Goldman–Hodgkin–Katz voltage equation, sometimes called the Goldman equation, is used in cell membrane physiology to determine the resting potential across a cell's membrane, taking into account all of the ions that are permeant through that membrane.
The discoverers of this are David E. Goldman of Columbia University, and the Medicine Nobel laureates Alan Lloyd Hodgkin and Bernard Katz.
Equation for monovalent ions
The GHK voltage equation for <math>n</math> monovalent positive ionic species <math>M_{i}</math> and <math>m</math> negative species <math>A_{j}</math>:
:<math>E_{m} = \frac{RT}{F} \ln{ \left( \frac{ \sum_{i}^{n} P_{M^{+}_{i[M^{+}_{i}]_\mathrm{out} + \sum_{j}^{m} P_{A^{-}_{j[A^{-}_{j}]_\mathrm{in{ \sum_{i}^{n} P_{M^{+}_{i[M^{+}_{i}]_\mathrm{in} + \sum_{j}^{m} P_{A^{-}_{j[A^{-}_{j}]_\mathrm{out \right) }</math>
This results in the following if we consider a membrane separating two <math>\mathrm{K}_{x}\mathrm{Na}_{1-x}\mathrm{Cl}</math>-solutions:
:<math>E_{m, \mathrm{K}_{x}\mathrm{\text{Na_{1-x}\mathrm{Cl} } = \frac{RT}{F} \ln{ \left( \frac{ P_{\text{Na[\text{Na}^{+}]_\mathrm{out} + P_{\text{K[\text{K}^{+}]_\mathrm{out} + P_{\text{Cl[\text{Cl}^{-}]_\mathrm{in} }{ P_{\text{Na[\text{Na}^{+}]_\mathrm{in} + P_{\text{K[\text{K}^{+}]_{\mathrm{in + P_{\text{Cl[\text{Cl}^{-}]_\mathrm{out} } \right) }</math>
It is "Nernst-like" but has a term for each permeant ion:
:<math>E_{m,\text{Na = \frac{RT}{F} \ln{ \left( \frac{ P_{\text{Na[\text{Na}^{+}]_\mathrm{out{ P_{\text{Na[\text{Na}^{+}]_\mathrm{in \right) }=\frac{RT}{F} \ln{ \left( \frac{ [\text{Na}^{+}]_\mathrm{out{ [\text{Na}^{+}]_\mathrm{in \right) }</math>
- <math>E_{m}</math> = the membrane potential (in volts)
- <math>P_\mathrm{ion}</math> = the membrane permeability for that ion
- <math>[\mathrm{ion}]_\mathrm{out}</math> = the extracellular concentration of that ion
- <math>[\mathrm{ion}]_\mathrm{in}</math> = the intracellular concentration of that ion (in the same units as <math>[\mathrm{ion}]_\mathrm{out}</math>)
- <math>R</math> = the ideal gas constant
- <math>T</math> = the temperature in kelvins
- <math>F</math> = Faraday's constant
The units for <math>P_\mathrm{ion}</math> and <math>[\mathrm{ion}]</math> are not important, as they divide out of the equation. Concentrations are commonly expressed in millimoles per liter (also written “millimolar” or “mM”). Permeabilities have units of meters per second. A Cartesian coordinate system is used to describe the system, with the z direction being perpendicular to the membrane. Assuming that the system is symmetrical in the x and y directions (around and along the axon, respectively), only the z direction need be considered; thus, the voltage E<sub>m</sub> is the integral of the z component of the electric field across the membrane.
According to Goldman's model, only two factors influence the motion of ions across a permeable membrane: the average electric field and the difference in ionic concentration from one side of the membrane to the other. The electric field is assumed to be constant across the membrane, so that it can be set equal to E<sub>m</sub>/L, where L is the thickness of the membrane. For a given ion denoted A with valence n<sub>A</sub>, its flux j<sub>A</sub>—in other words, the number of ions crossing per time and per area of the membrane—is given by the formula
:<math>
j_{\mathrm{A = -D_{\mathrm{A
\left( \frac{d\left[ \mathrm{A}\right]}{dz} - \frac{n_{\mathrm{AF}{RT} \frac{E_{m{L} \left[ \mathrm{A}\right] \right)
</math>
The first term corresponds to Fick's law of diffusion, which gives the flux due to diffusion down the concentration gradient, i.e., from high to low concentration. The constant D<sub>A</sub> is the diffusion constant of the ion A. The second term reflects the flux due to the electric field, which increases linearly with the electric field; Formally, it is [A] multiplied by the drift velocity of the ions, with the drift velocity expressed using the Stokes–Einstein relation applied to electrophoretic mobility. The constants here are the charge valence n<sub>A</sub> of the ion A (e.g., +1 for K<sup>+</sup>, +2 for Ca<sup>2+</sup> and −1 for Cl<sup>−</sup>), the temperature T (in kelvins), the molar gas constant R, and the faraday F, which is the total charge of a mole of electrons.
This is a first-order ODE of the form y' = ay + b, with y = [A] and y = d[A]/dz; integrating both sides from z=0 to z=L with the boundary conditions [A](0) = [A]<sub>in</sub> and [A](L) = [A]<sub>out</sub>, one gets the solution
:<math>
j_{\mathrm{A = \mu n_{\mathrm{A P_{\mathrm{A
\frac{\left[ \mathrm{A}\right]_{\mathrm{out - \left[ \mathrm{A}\right]_{\mathrm{in e^{n_{\mathrm{A\mu} }{1 - e^{n_{\mathrm{A\mu
</math>
where μ is a dimensionless number
:<math>
\mu = \frac{F E_{m{RT}
</math>
and P<sub>A</sub> is the ionic permeability, defined here as
:<math>
P_{\mathrm{A = \frac{D_{\mathrm{A}{L}
</math>
The electric current density J<sub>A</sub> equals the charge q<sub>A</sub> of the ion multiplied by the flux j<sub>A</sub>
:<math>
J_{A} = q_{\mathrm{A j_{\mathrm{A
</math>
Current density has units of (Amperes/m<sup>2</sup>). Molar flux has units of (mol/(s m<sup>2</sup>)). Thus, to get current density from molar flux one needs to multiply by Faraday's constant F (Coulombs/mol). F will then cancel from the equation below. Since the valence has already been accounted for above, the charge q<sub>A</sub> of each ion in the equation above, therefore, should be interpreted as +1 or −1 depending on the polarity of the ion.
There is such a current associated with every type of ion that can cross the membrane; this is because each type of ion would require a distinct membrane potential to balance diffusion, but there can only be one membrane potential. By assumption, at the Goldman voltage E<sub>m</sub>, the total current density is zero
:<math>
J_{tot} = \sum_{A} J_{A} = 0
</math>
(Although the current for each ion type considered here is nonzero, there are other pumps in the membrane, e.g. Na<sup>+</sup>/K<sup>+</sup>-ATPase, not considered here which serve to balance each individual ion's current, so that the ion concentrations on either side of the membrane do not change over time in equilibrium.) If all the ions are monovalent—that is, if all the n<sub>A</sub> equal either +1 or −1—this equation can be written
:<math>
w - v e^{\mu} = 0
</math>
whose solution is the Goldman equation
:<math>
\frac{F E_{m{RT} = \mu = \ln \frac{w}{v}
</math>
where
:<math>
w = \sum_{\mathrm{cations\ C P_{\mathrm{C \left[ \mathrm{C}^{+} \right]_{\mathrm{out +
\sum_{\mathrm{anions\ A P_{\mathrm{A \left[ \mathrm{A}^{-} \right]_{\mathrm{in
</math>
:<math>
v = \sum_{\mathrm{cations\ C P_{\mathrm{C \left[ \mathrm{C}^{+} \right]_{\mathrm{in +
\sum_{\mathrm{anions\ A P_{\mathrm{A \left[ \mathrm{A}^{-} \right]_{\mathrm{out
</math>
If divalent ions such as calcium are considered, terms such as e<sup>2μ</sup> appear, which is the square of e<sup>μ</sup>; in this case, the formula for the Goldman equation can be solved using the quadratic formula.
See also
- Bioelectronics
- Cable theory
- GHK current equation
- Hindmarsh–Rose model
- Hodgkin–Huxley model
- Morris–Lecar model
- Nernst equation
- Saltatory conduction
References
External links
- Subthreshold membrane phenomena Includes a well-explained derivation of the Goldman-Hodgkin-Katz equation
- Nernst/Goldman Equation Simulator
- Goldman-Hodgkin-Katz Equation Calculator
- Nernst/Goldman interactive Java applet The membrane voltage is calculated interactively as the number of ions are changed between the inside and outside of the cell.
- Potential, Impedance, and Rectification in Membranes by Goldman (1943)