University of Balamand September 13, 2010

Faculty of Medicine and Medical Sciences

Dr. M. Khachab
GPHY 402

Ionic Equilibria

Principles of
Equilibria

Learning Objectives

1. Define the electrochemical potential (µ) of an ion

2. Write the equation for the difference between the
electrochemical potential of an ion on one side of a
membrane and that on the other side of the membrane (∆µ)
¾ What does it mean?
3. Use the Nernst Equation to determine whether an ion is in
equilibrium
¾ If the ion is not in equilibrium, determine in which
direction the ion will tend to flow
4. Compute the electrical potential difference across a
membrane that is permeable to only one ionic species
5. Identify the Gibbs-Donnan Equilibrium and explain its
implications for distribution of ions and water between the
cytosol and extracellular fluid

Ionic Equilibria Page

University of Balamand September 13, 2010
Faculty of Medicine and Medical Sciences
Dr. M. Khachab
GPHY 402

Principles of Equilibria

I. The Electrochemical
Potential of an Ion

In Which Way Will an Ion Flow

Spontaneously?
In situation 1:
ƒ Na+ will tend to flow from A
to B because of both the
force of diffusion
(concentration gradient) and
the electrical force (electrical
potential difference or voltage
gradient)

In situation 2:
ƒ Na+ will tend to flow
¾ from A to B because of
the force of diffusion
(concentration gradient)
and
¾ from B to A because of
the electrical force
(electrical potential
difference or voltage
gradient)

Ionic Equilibria Page

University of Balamand September 13, 2010
Faculty of Medicine and Medical Sciences
Dr. M. Khachab
GPHY 402

In Which Way Will Na+ Net Flow Occur in

Situation 2 ?
ƒ The force of diffusion and
the electrical force are
opposing forces
ƒ In order to know whether a
net flow of Na+ will occur,
and if so, in which
direction, we need to
quantitatively compare
the strength of the
opposing forces
¾ Electrochemical
potential (µ) of an ion

The Electrochemical Potential (µ) of an

Ion
ƒ Defined as:
µ = µo+RTlnC +zFE

¾µo is the electrochemical potential in a

reference state (1M concentration at 20oC)
¾R is the ideal gas constant
¾T is the absolute temperature (0K)
¾C is the concentration of the ion (mole/L)
¾z is the valence of the ion
¾F is Faraday’s Number ( 96,500
coulomb/mole)
¾E is the electrical potential (in volts)
ƒ µ has units of energy/mole

Ionic Equilibria Page

University of Balamand September 13, 2010
Faculty of Medicine and Medical Sciences
Dr. M. Khachab
GPHY 402

The Electrochemical Potential (µ) of an Ion

µ = µo + RTlnC + zFE

¾ RTlnC is the concentration term

¾ zFE is the electrical term
¾ RTlnC is the energy that 1 mole of ions possesses due
to concentration
¾ zFE is the energy that 1 mole of ions possesses due to
the electrical potential

The Electrochemical Potential of an Ion

Across a Membrane (∆µ)

ƒ µA = µo + RTlnCA + zFEA
ƒ µB = µo + RTlnCB + zFEB

ƒ ∆µ = µ(A) - µ(B)

ƒ ∆µ = RT ln (C(A) / C(B))
+ zF (EA – EB)

Ionic Equilibria Page

University of Balamand September 13, 2010
Faculty of Medicine and Medical Sciences
Dr. M. Khachab
GPHY 402

Meaning of ∆µ

∆µ =RT ln (C(A) / C(B)) + zF(EA – EB)

ƒ RT ln (C(A) / C(B)) is the energy difference between a

mole of ions on side A and a mole of ions on side B as
a result of the concentration difference
ƒ zF(EA – EB) is the energy difference between a mole of
ions on side A and a mole of ions on side B as a result
of the electrical potential difference
ƒ A positive value of ∆µ indicates a greater
electrochemical potential on side A than on side B
ƒ A negative value of ∆µ indicates a greater
electrochemical potential on side B than on side A

Meaning of ∆µ

∆µ =RT ln (C(A) / C(B)) + zF(EA – EB)

ƒ The net flow of an ion will spontaneously occur from
where its µ is higher to where its µ is lower
ƒ RTln(C(A) /C(B)) is the tendency of the ion to flow because
of the concentration gradient (Force of diffusion)
ƒ zF(EA - EB) is the tendency of the ion to flow because of
the electrical potential difference (Electrical force)
ƒ A positive value of ∆µ indicates a tendency for the ion to
flow from A to B
ƒ A negative value of of ∆µ indicates a tendency for the ion
to flow from B to A

Ionic Equilibria Page

University of Balamand September 13, 2010
Faculty of Medicine and Medical Sciences
Dr. M. Khachab
GPHY 402

Principles of Equilibria

II. Electrochemical
Equilibrium

An Ion in Electrochemical Equilibrium

∆µ = RT ln (C(A) / C(B)) + zF(EA – EB)

ƒ At equilibrium, ∆µ=0
¾ Equilibrium occurs when the force of diffusion and
the electrical force are equal in magnitude but
opposite in direction
ƒ When an ion is in electrochemical equilibrium across a
membrane between side A and side B:
¾Its electrochemical potential on side A is equal to
that on side B
¾Net force on the ion = 0
¾The ion has no net tendency to flow in either
direction

Ionic Equilibria Page

University of Balamand September 13, 2010
Faculty of Medicine and Medical Sciences
Dr. M. Khachab
GPHY 402

Electrochemical Equilibrium and the

Nernst Equation
∆µ = RT ln (C(A) / C(B)) + zF (EA – EB) = 0

EA – EB = (-RT/zF) ln (C(A) / C(B)) = (RT/zF) ln (C(B) / C(A))

This is the Nernst Equation
ƒ The Nernst Equation allows to calculate the electrical
potential difference (EA – EB) that just balances a
particular concentration ratio provided the force of
diffusion and the electrical force are in opposite directions
ƒ The Nernst Equation holds ONLY for an ion that is in
electrochemical equilibrium
ƒ Any ion that is in electrochemical equilibrium will
satisfy the Nernst Equation

The Nernst Equation

EA – EB = (-RT/zF) ln (C(A)/ C(B)) = (RT/zF) ln (C(B) /C(A))

¾ ln(x) = 2.303 log(x)

¾ 2.303RT/F ~= 60 mV

ƒ A useful form of the Nernst Equation:

EA – EB = (-60mV/z) log (C(A) / C(B))
or
EA – EB = (60mV/z) log (C(B)/C(A))

Ionic Equilibria Page

University of Balamand September 13, 2010
Faculty of Medicine and Medical Sciences
Dr. M. Khachab
GPHY 402

Examples of Uses of the Nernst Equation

ƒQuestion: If K+ is in equilibrium
A B
across the membrane,calculate
EA – EB?
0.1 M KCl 0.01 M KCl

EA – EB = (-60mV/z) log(C(A)/ C(B)) = (-60mV/+1) log (0.1/0.01)

EA – EB = (-60mV/+1) log(10) = -(60mV)(1) = -60 mV

The Nernst equation tells us that at equilibrium, side A must be

60 mV negative relative to side B

Examples of Uses of the Nernst Equation

A + - B
+ - Question: is Cl- in
1 M KCl + - 0.1 M KCl electrochemical equilibrium
+ - across the membrane in the
+ -
situation shown in the figure?
100 mV
ƒ EA – EB = (-60mv/z) log (C(A) /C(B) )= (-60mV/-1)log (1/0.1)
EA – EB = (-60mv/-1) log (10)= (60mV)(1) = +60mV
If EA – EB were +60 mV, the electrical force and the
diffusion forces would be equal in magnitude but
opposite in direction
ƒ However, the measured electrical potential difference EA
– EB across the membrane is +100mv
¾ Therefore, Cl- is not in electrochemical equilibrium
across the membrane

Ionic Equilibria Page

University of Balamand September 13, 2010
Faculty of Medicine and Medical Sciences
Dr. M. Khachab
GPHY 402

Examples of Uses of the Nernst Equation

A + - B
+ -
1 M KCl + - 0.1 M KCl
+ -
+ -

100 mV
ƒ Cl- is
not in electrochemical equilibrium across the
membrane
ƒ Question: How could we determine then the direction of
net Cl- flow?
¾ When ions are not in equilibrium, the Nernst
Equation can be used to predict the direction in
which ions will flow
¾ Cl- net flow will be from B to A

Using the Nernst Equation

ƒ The Nernst Equation indicates what the membrane

electrical potential would have to be in order for an ion
to be in electrochemical equilibrium
¾The Nernst Equation gives a theoretical number
ƒ However, we can measure by a voltmeter the
membrane electrical potential
¾The measurement gives a real number
‰ Compare the potential calculated using the Nernst
Equation with the actual (measured) membrane
electrical potential to predict the direction in which
ions tend to flow

Ionic Equilibria Page

University of Balamand September 13, 2010
Faculty of Medicine and Medical Sciences
Dr. M. Khachab
GPHY 402

Using The Nernst Equation

ƒ If E measured = E calculated from the Nernst Equation

(equilibrium potential for the ion), the ion is in electrochemical
equilibrium
ƒ If E measured is of the same sign as E calculated, but
smaller in magnitude, then the force of diffusion
determines the direction of net ion flow
ƒ If E measured is of the same sign as E calculated, but
larger in magnitude, then the electrical force determines the
direction of net ion flow
ƒ If E measured is opposite in sign to E calculated, then the
electrical force and diffusion force are in same direction
¾ That ion cannot be in equilibrium
¾ The ion will tend to flow in the direction determined by both
the electrical and diffusion forces

Principles of Equilibria

III. The Gibbs-Donnan

Equilibrium

Ionic Equilibria Page

University of Balamand September 13, 2010
Faculty of Medicine and Medical Sciences
Dr. M. Khachab
GPHY 402

The Gibbs-Donnan Equilibrium

ƒ The cytosol contains some ionic species to which the

plasma membrane is permeable, and others to which the
plasma membrane is impermeable
ƒ The cytosol has a significant concentration of charged,
impermeant macromolecules, such as proteins and
nucleic acids
¾ These are predominantly anionic (negatively charged)
ƒ The presence of impermeant ionic species influences the
equilibrium distribution of permeant ionic species

A Gibbs-Donnan Model Situation

ƒ The membrane is permeable to
K+ and Cl-, but is impermeable to
X-
ƒ There is no electrical potential
difference across the membrane
ƒ Cl- has a tendency to flow from B
to A
¾ As Cl- flows from B to A, an
electrical potential
difference builds up across
the membrane (side A
becomes negative with
respect to side B)
¾ This electrical potential
difference provides a driving
force for K+ to flow from B to A

Ionic Equilibria Page

University of Balamand September 13, 2010
Faculty of Medicine and Medical Sciences
Dr. M. Khachab
GPHY 402

When Will Cl- and K+ Stop Flowing?

ƒ Given enough time, Cl- and K+ will come into
equilibrium
¾Cl- and K+ will stop flowing
¾Cl- and K+ will satisfy the Nernst Equation
¾At equilibrium, both ∆µK+ and ∆µCl- must
equal 0

∆µK+ = RTln([K+]A / [K+]B) + F(EA – EB) = 0

∆µCl- = RTln([Cl-]A/[Cl-]B) - F(EA – EB) = 0

The Gibbs-Donnan Equation or Donnan

Relation

∆µK = RTln([K+]A / [K+]B) + F(EA – EB) = 0

∆µCl = RTln([Cl-]A/[Cl-]B) - F(EA – EB) = 0

ƒ Add the two equations, divide by RT, take antilogs of both

sides, cross-multiply, and we obtain:

[K+]A [Cl-]A = [K+]B [Cl-]B

¾ This is the Donnan Relation or the Gibbs-Donnan

Equation
¾ Satisfying the Donnan Relation means that both ions
are in equilibrium
¾ Equation holds for any univalent cation and anion pair
in equilibrium

Ionic Equilibria Page

University of Balamand September 13, 2010
Faculty of Medicine and Medical Sciences
Dr. M. Khachab
GPHY 402

How Much Cl- and K+ Will Flow to Attain

the Gibbs Donnan Equilibrium?
ƒ The Principle of Electroneutrality
states that in any macroscopic
volume of solution, the number
of positive and negative charges
must be equal
¾ The number of Cl- ions that
flows from B to A must be the
same number of K+ ions that
flows from B to A
‰ In reality, the number of Cl-
ions that flows from B to A
will be infinitesimally larger
than the number of K+ ions
that flows from B to A
‰ However, in chemical terms,
the difference between the
number of Cl- and K+ ions
that flow is insignificant

How Much Cl- and K+ Will Flow to Attain

the Gibbs Donnan Equilibrium?
ƒ Assume A and B have equal
volumes
ƒ If the decrease in [Cl-] and
[K+] in B are equal to Z, then
[K+] and [Cl-] in A increase
by Z
‰[X-] cannot change
ƒ Applying the Gibbs-Donnan
Equation:
[K+]A[Cl-]A = [K+]B[Cl-]B

¾ (0.1 +Z)(Z) =(0.1 –Z)2

¾ Z = 0.0333…

Ionic Equilibria Page

University of Balamand September 13, 2010
Faculty of Medicine and Medical Sciences
Dr. M. Khachab
GPHY 402

Ion Concentrations After Gibbs Donnan

Equilibrium has been Attained
ƒ There is a higher [K+] in A
than in B
ƒ There is a higher [Cl-] in B
than in A
ƒ If K+ and Cl- are in
electrochemical equilibrium,
both ions satisfy the Nernst
Equation
ƒ Applying the Nernst
Equation results in :
EA - EB = - 18 mV

Osmotic Imbalance
ƒ The sum of [K+] and [Cl-] in A is
greater than their sum in B
ƒ X- present in A, but not in B
ƒ Consequently, there is a higher
concentration of osmotically
active ions in A than in B
ƒ Water will tend to flow by
osmosis from B to A until the
total osmotic pressure of the 2
solutions is equal
ƒ Unless it is restrained, all the
water from B will end up on A

Ionic Equilibria Page

University of Balamand September 13, 2010
Faculty of Medicine and Medical Sciences
Dr. M. Khachab
GPHY 402

Osmotic Imbalance
ƒ Water can be restrained
from moving by enclosing
solution A in a rigid
container
ƒ As water flows from B to
A, pressure will build up
in A
¾ A hydrostatic pressure
of 2.99 atmospheres is
required to prevent
water from flowing
from B to A in the
Gibbs-Donnan
equilibrium

How do Cells Cope with the Osmotic

Consequences of the Gibbs-Donnan Equilibrium?

ƒ Plant cells have a rigid cell wall that restrains the movement of
water
¾ The cell wall allows turgor pressure to build up in the cell
‰ If the cell wall were not present, the Gibbs-Donnan Equilibrium
would cause osmotic pressure in the cytoplasm to build up in
excess of the osmotic pressure in the extracellular fluid
‰ This build-up of pressure would threaten the maintenance of the
normal cellular volume
ƒ Animal cells have evolved ion transport processes to deal with
the osmotic consequences of the Gibbs-Donnan equilibrium
¾ The Na+-K+-ATPase in the plasma membrane pumps Na+ out of
the cytoplasm into the extracellular fluid (ECF)
¾ The extrusion of Na+ decreases the osmotic pressure of the
cytoplasm and increases the osmotic pressure of the ECF
‰ If ion transport mechanisms were not present, the osmotic
imbalance caused by the Gibbs-Donnan Equilibrium would cause
animal cells to swell and finally burst

Ionic Equilibria Page

University of Balamand September 13, 2010
Faculty of Medicine and Medical Sciences
Dr. M. Khachab
GPHY 402

Features of the Gibbs-Donnan Equilibrium

ƒ The side with the impermeant anions (that corresponds

to the cytosol) has the following features:
¾ A greater concentration of mobile cations
¾ A smaller concentration of mobile anions
¾ A negative electrical potential with respect to
the other side of the membrane
¾ A greater osmotic pressure

References

ƒ Chapter 5: Membrane Potentials and Action Potentials in

Textbook of Medical Physiology by Guyton and Hall

ƒ Chapter 7: Membrane Potential in Principles of Neural

Science. Edited by Eric R. Kandel, James H. Schwartz,
and Thomas M. Jessell.

Ionic Equilibria Page