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Goldman–Hodgkin–Katz flux equation
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<h2 id="origin">Origin</h2> <p>The American <a href="/facts/David_E._Goldman/SvIgpqSe">David E. Goldman</a> of <a href="/facts/Columbia_University/Hlf1gw53">Columbia University</a>, and the English Nobel laureates <a href="/facts/Alan_Lloyd_Hodgkin/YUY3C2Hd">Alan Lloyd Hodgkin</a> and <a href="/facts/Bernard_Katz/3FMvw2bM">Bernard Katz</a> derived this equation. </p> <h2 id="assumptions">Assumptions</h2> <p>Several assumptions are made in deriving the GHK flux equation (Hille 2001, p. 445) : </p> <ul><li>The membrane is a homogeneous substance</li> <li>The electrical field is constant so that the transmembrane potential varies linearly across the membrane</li> <li>The ions access the membrane instantaneously from the intra- and extracellular solutions</li> <li>The permeant ions do not interact</li> <li>The movement of ions is affected by both concentration and voltage differences</li></ul> <h2 id="equation">Equation</h2> <p>The GHK flux equation for an ion S (Hille 2001, p. 445): </p> Φ S = P S z S 2 V m F 2 R T [ S ] i − [ S ] o exp ( − z S V m F / R T ) 1 − exp ( − z S V m F / R T ) {\displaystyle \Phi _{S}=P_{S}z_{S}^{2}{\frac {V_{m}F^{2}}{RT}}{\frac {[{\mbox{S}}]_{i}-[{\mbox{S}}]_{o}\exp(-z_{S}V_{m}F/RT)}{1-\exp(-z_{S}V_{m}F/RT)}}} <p>where </p> <ul><li><i> Φ {\displaystyle \Phi } </i>S is the current density (flux) outward through the membrane carried by ion S, measured in <a href="/facts/Ampere/MScqkCgz">amperes</a> per square meter (A·m−2)</li> <li><i>P</i>S is the permeability of the membrane for ion S measured in m·s−1</li> <li><i>z</i>S is the valence of ion S</li> <li><i>V</i>m is the transmembrane potential in <a href="/facts/Volt/KF18MXP2">volts</a></li> <li><i>F</i> is the <a href="/facts/Faraday_constant/8AXVov0J">Faraday constant</a>, equal to 96,485 C·mol−1 or J·V−1·mol−1</li> <li><i>R</i> is the <a href="/facts/Gas_constant/RUXszrMH">gas constant</a>, equal to 8.314 J·K−1·mol−1</li> <li><i>T</i> is the <a href="/facts/Absolute_temperature/JXeJJPa6">absolute temperature</a>, measured in <a href="/facts/Kelvin/E3trzC4C">kelvins</a> (= degrees Celsius + 273.15)</li> <li>[S]i is the intracellular concentration of ion S, measured in mol·m−3 or mmol·l−1</li> <li>[S]o is the extracellular concentration of ion S, measured in mol·m−3</li></ul> <h2 id="implicit-definition-of-reversal-potential">Implicit definition of reversal potential</h2> <p>The <a href="/facts/Reversal_potential/3RIv3RTd">reversal potential</a> is shown to be contained in the GHK flux equation (Flax 2008). The proof is replicated from the reference (Flax 2008) here. </p><p>We wish to show that when the flux is zero, the transmembrane potential is not zero. Formally it is written lim Φ S → 0 V m ≠ 0 {\displaystyle \lim _{\Phi _{S}\rightarrow 0}V_{m}\neq 0} which is equivalent to writing lim V m → 0 Φ S ≠ 0 {\displaystyle \lim _{V_{m}\rightarrow 0}\Phi _{S}\neq 0} , which states that when the transmembrane potential is zero, the flux is not zero. </p><p>However, due to the form of the GHK flux equation when V m = 0 {\displaystyle V_{m}=0} , Φ S = 0 0 {\displaystyle \Phi _{S}={\frac {0}{0}}} . This is a problem as the value of 0 0 {\displaystyle {\frac {0}{0}}} is <a href="/facts/Indeterminate_form/5Y3JWKjS">indeterminate</a>. </p><p>We turn to <a href="/facts/L%2527H%25C3%25B4pital%2527s_rule/pCXK75Io">l'Hôpital's rule</a> to find the solution for the limit: </p> lim V m → 0 Φ S = P S z S 2 F 2 R T [ V m ( [ S ] i − [ S ] o exp ( − z S V m F / R T ) ) ] ′ [ 1 − exp ( − z S V m F / R T ) ] ′ {\displaystyle \lim _{V_{m}\rightarrow 0}\Phi _{S}=P_{S}{\frac {z_{S}^{2}F^{2}}{RT}}{\frac {[V_{m}([{\mbox{S}}]_{i}-[{\mbox{S}}]_{o}\exp(-z_{S}V_{m}F/RT))]'}{[1-\exp(-z_{S}V_{m}F/RT)]'}}} <p>where [ f ] ′ {\displaystyle [f]'} represents the differential of f and the result is : </p> lim V m → 0 Φ S = P S z S F ( [ S ] i − [ S ] o ) {\displaystyle \lim _{V_{m}\rightarrow 0}\Phi _{S}=P_{S}z_{S}F([{\mbox{S}}]_{i}-[{\mbox{S}}]_{o})} <p>It is evident from the previous equation that when V m = 0 {\displaystyle V_{m}=0} , Φ S ≠ 0 {\displaystyle \Phi _{S}\neq 0} if ( [ S ] i − [ S ] o ) ≠ 0 {\displaystyle ([{\mbox{S}}]_{i}-[{\mbox{S}}]_{o})\neq 0} and thus </p> lim Φ S → 0 V m ≠ 0 {\displaystyle \lim _{\Phi _{S}\rightarrow 0}V_{m}\neq 0} <p>which is the definition of the reversal potential. </p><p>By setting Φ S = 0 {\displaystyle \Phi _{S}=0} we can also obtain the reversal potential : </p> Φ S = 0 = P S z S 2 F 2 R T V m ( [ S ] i − [ S ] o exp ( − z S V m F / R T ) ) 1 − exp ( − z S V m F / R T ) {\displaystyle \Phi _{S}=0=P_{S}{\frac {z_{S}^{2}F^{2}}{RT}}{\frac {V_{m}([{\mbox{S}}]_{i}-[{\mbox{S}}]_{o}\exp(-z_{S}V_{m}F/RT))}{1-\exp(-z_{S}V_{m}F/RT)}}} <p>which reduces to : </p> [ S ] i − [ S ] o exp ( − z S V m F / R T ) = 0 {\displaystyle [{\mbox{S}}]_{i}-[{\mbox{S}}]_{o}\exp(-z_{S}V_{m}F/RT)=0} <p>and produces the <a href="/facts/Nernst_equation/bCMCjfqx">Nernst equation</a> : </p> V m = − R T z S F ln ( [ S ] i [ S ] o ) {\displaystyle V_{m}=-{\frac {RT}{z_{S}F}}\ln \left({\frac {[{\mbox{S}}]_{i}}{[{\mbox{S}}]_{o}}}\right)} <h2 id="rectification">Rectification</h2> <p>Since one of the assumptions of the GHK flux equation is that the ions move independently of each other, the total flow of ions across the membrane is simply equal to the sum of two oppositely directed fluxes. Each flux approaches an <a href="/facts/Asymptote/nvLPuxKa">asymptotic value</a> as the membrane potential diverges from zero. These asymptotes are </p> Φ S | i → o = P S z S 2 V m F 2 R T [ S ] i for V m ≫ 0 {\displaystyle \Phi _{S|i\to o}=P_{S}z_{S}^{2}{\frac {V_{m}F^{2}}{RT}}[{\mbox{S}}]_{i}\ {\mbox{for}}\ V_{m}\gg \;0} Φ S | i → o = 0 for V m ≪ 0 {\displaystyle \Phi _{S|i\to o}=0\;{\mbox{for}}\ V_{m}\ll \;0} <p>and </p> Φ S | o → i = P S z S 2 V m F 2 R T [ S ] o for V m ≪ 0 {\displaystyle \Phi _{S|o\to i}=P_{S}z_{S}^{2}{\frac {V_{m}F^{2}}{RT}}[{\mbox{S}}]_{o}\ {\mbox{for}}\ V_{m}\ll \;0} Φ S | o → i = 0 for V m ≫ 0 {\displaystyle \Phi _{S|o\to i}=0\;{\mbox{for}}\ V_{m}\gg \;0} <p>where subscripts 'i' and 'o' denote the intra- and extracellular compartments, respectively. Intuitively one may understand these limits as follows: if an ion is only found outside a cell, then the flux is Ohmic (proportional to voltage) when the voltage causes the ion to flow into the cell, but no voltage could cause the ion to flow out of the cell, since there are no ions inside the cell in the first place. </p><p>Keeping all terms except <i>V</i>m constant, the equation yields a straight line when plotting <i> Φ {\displaystyle \Phi } </i>S against <i>V</i>m. It is evident that the ratio between the two asymptotes is merely the ratio between the two concentrations of S, [S]i and [S]o. Thus, if the two concentrations are identical, the slope will be identical (and constant) throughout the voltage range (corresponding to <a href="/facts/Ohm%2527s_law/PjfEyTgI">Ohm's law</a> scaled by the surface area). As the ratio between the two concentrations increases, so does the difference between the two slopes, meaning that the current is larger in one direction than the other, given an equal <a href="/facts/Force/533Q1uzq">driving force</a> of opposite signs. This is contrary to the result obtained if using Ohm's law scaled by the surface area, and the effect is called <a href="/facts/Rectifier/me8XDxND">rectification</a>. </p><p>The GHK flux equation is mostly used by <a href="/facts/Electrophysiology/VPd5VYzm">electrophysiologists</a> when the ratio between [S]i and [S]o is large and/or when one or both of the concentrations change considerably during an <a href="/facts/Action_potential/Sz8yCRqx">action potential</a>. The most common example is probably intracellular <a href="/facts/Calcium/hf252CC0">calcium</a>, [Ca2+]i, which during a <a href="/facts/Cardiac_action_potential/CJu2rTR8">cardiac action potential</a> cycle can change 100-fold or more, and the ratio between [Ca2+]o and [Ca2+]i can reach 20,000 or more. </p> <ul><li><a href="/facts/Bertil_Hille/ht5Q4y92">Hille, Bertil</a> (2001). <i>Ion channels of excitable membranes</i>, 3rd ed., Sinauer Associates, Sunderland, Massachusetts. <a href="/facts/ISBN_(identifier)/15AdSPa9">ISBN</a> 978-0-87893-321-1</li> <li>Flax, Matt R. and Holmes, W.Harvey (2008). <i>Goldman-Hodgkin-Katz Cochlear Hair Cell Models – a Foundation for Nonlinear Cochlear Mechanics</i>, Conference proceedings: Interspeech 2008.</li></ul> <h2 id="see-also">See also</h2> <ul><li><a href="/facts/Goldman_equation/DFFHkVBM">Goldman equation</a></li> <li><a href="/facts/Nernst_equation/bCMCjfqx">Nernst equation</a></li> <li><a href="/facts/Reversal_potential/3RIv3RTd">Reversal potential</a></li></ul>