The membrane Resting Membrane Potential Animation

Resting Membrane Potential
and
Action Potential
Lipid monolayer
Irving Langmuir:
- - American physico chemist
- - 1932 Nobel-prise in chemistry
- - 1917: lipids form a monolayer on the surface of the water
Lipid bilayer
Gortel and Grendel:
1925: there is twice as much lipid
in the membrane of blood cells
than needed
Bódis Emőke
13 October 2011
Resting Membrane Potential
The membrane
The chemical composition of the cell
• Water
• Kations: K + , Na + , Ca 2+
• Anions: Cl - , H 2 PO 4 - , HPO4 2-
• Protein-anions
– Localise mainly intracellularly
– for which membrane is impermeable
– Isoelectric point
Animation
http://www.youtube.com/watch?v=YP_P6bYvEjE&hd=1
1

Resting Membrane Potential
Na +
Outside
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
A -
K + Cl- 142 mEq/L
4 mEq/L
K +
140 mEq/L
Cl -
Na Inside
+
14 mEq/L
Resting Membrane Potential
Outside
A -
K + Cl- 142 mEq/L
4 mEq/L
K +
140 mEq/L
Cl -
Na +
Na Inside
+
14 mEq/L
Resting Membrane Potential
Outside
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
A -
K + Cl- 142 mEq/L
4 mEq/L
K +
140 mEq/L
Na +
Na Inside
+
14 mEq/L
• Make cell membrane SELECTIVELY permeable to K+
• K+ wants to move toward region of lower concentration
(CHEMICAL FORCE to move down concentration gradient)
Cl -
Resting Membrane Potential
Typical:
-30 - 90 mV
Na +
Outside
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
A -
K + Cl- 142 mEq/L
4 mEq/L
K +
140 mEq/L
Cl -
Na Inside
+
14 mEq/L
• If electrode is inserted into cardiac cell, will detect a
negative reading compared to outside of the cell of -80mV
The electric field strength: 70 mM/5 nm = 140 000 V/cm
Resting Membrane Potential
Outside
A -
K + Cl- 142 mEq/L
4 mEq/L
K +
140 mEq/L
Cl -
Na +
Na Inside
+
14 mEq/L
• Make cell membrane SELECTIVELY permeable to K+
• K+ wants to move toward region of lower concentration
(CHEMICAL FORCE to move down concentration gradient)
Resting Membrane Potential
Na +
Outside
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
A -
K + Cl- 142 mEq/L
4 mEq/L
K +
140 mEq/L
Cl -
Na Inside
+
14 mEq/L
• As K + leaves cell, negativity increases on the inside
of the cell membrane and electrostatically attracts K + .
This electrostatic force prevents K + from leaving cell.
2

Resting Membrane Potential
Na +
Outside
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
A -
Chemical driving force is
eventually balanced by
K + Cl- 142 mEq/L
4 mEq/L
K +
140 mEq/L
Cl -
Nernst Equation
chemical potential ⇒ W chem = NRT ln (X1/X2)
Na Inside
+
14 mEq/L
Electrical driving force so no
further net movement of K +
N = number of moles associated with the concentration gradient
R = gas constant
T = absolute temperature
X1 / X2 = concentration gradient
electic potential ⇒ W el = NzF ΔE
N = number of moles of the charged particles
z = valency
F = Faraday’s number
∆E (= E 1-E 2 ) = strength of the electric field (V)
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Nernst Equation
NzFE = NRT ln X 1
X 2
zFE = RT ln X 1
X 2
E = RT
zF ln X 1
X 2
Forces controlling the movements of
charged particles
Chemical potential: (Willard Gibbs (1876) - American mathematical physicist)
The chemical potential of a thermodynamic system is the amount of energy by which
the system would change if an additional particle were introduced (number of the
particles!).
Concentration gradient → diffusion: moving the particles from a high concentration
area to a low one → diffusion potential.
Electric potential: the difference in electrical charge between two points in a circuit
expressed in volts.
Electrical gradients: An electric field creates a force that can move the charged(+ or -)
particles (the work of the electric field) → electric current: moving charged particles.
Electro-chemical potential
The combination (sum) of the chemical and the electric potential. Related to the
average energy affecting the charged particle.
A little bit more about the Nernst Equation
Nernst Equation
The general form of the equation in your
textbook:
What is the meaning of E x?
E x is the potential at which the flux due to diffusion is equal and
opposite to the flux due to electrophoresis
What is E K for the cell we showed at the beginning?
3

In our cell why was the resting potential -80mV if E K = -100mV?
This cell is permeable to more than one
ionic species at rest.
How can we quantify the contribution of multiple ionic species?
The Goldman Equation (or the GHK Equation)
Some important details:
• Derives from the Nernst equation and a few assumptions
• Uses permeabilities rather than conductances
• Cl- is flipped to account for a -1 valence
Goldman-Hodgkin-Katz Equation
Good agreement with the measured value.
Donnan-potential
A negative non-diffusing charge on one side of a membrane
potential gradient across the membrane from which ions will diffuse.
The result will be an electrochemical equilibrium.
The concentration (chemical potential) of ions will not necessarily be the same
inside and outside. Thus, as an electrical disequilibrium is maintained because of
diffusing charges.
Goldman-Hodgkin-Katz Equation
To determine the potential across a cell's membrane taking
into account all of the ions with different permeabilities
through the membrane.
permeability of the given ion inside and outside concentrations
If the membrane is not permeable for an ion:
Donnan-potential
Donnan equilibrium: characterising the equlibrium situation when
the membrane is not permeable for some ionic components.
Unequal distribution of diffusible ions
between two ionic solutions
separated by a membrane
impermeable to at least one of the ionic
species present (e.g. proteins)
Donnan-potential
In a Donnan equilibrium, the charge imbalance in the vicinity of a semi-permeable
membrane gives rise to an electric field, with a jump in the electrostatic potential
typically occurring over a length of less than a micrometer.
Similarly, if a colloidal suspension has a gradient of concentration (such as is
produced in sedimentation or centrifugation), then a macroscopic electric field is
generated by the charge imbalance appearing at the top and bottom of the sample
column.
4

Resting Membrane Potential
Na +
Outside
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
A -
K + Cl- 142 mEq/L
4 mEq/L
K +
140 mEq/L
Cl -
Na Inside
+
14 mEq/L
Animation
http://bcs.whfreeman.com/thelifewire/content/chp44/4401s.swf
Na + , K + - ATPase Pump
Resting Membrane Potential
Na +
Outside
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
A -
K + Cl- 142 mEq/L
4 mEq/L
K +
140 mEq/L
Cl -
Na Inside
+
14 mEq/L
• There is a small, but finite, leakage of Na + into cell
(depolarizing effect)
Resting Membrane Potential
• Potassium is the major determinant of the
Resting Membrane Potential
• Potassium and sodium ion channels allow
leakage of these ions across the cell membranes
• In the normal nerve fiber, the permeability of the
membrane to potassium is about 100 times as
great as to sodium
Na + , K + - ATPase Pump
(Sodium Pump)
a highly-conserved integral membrane protein
is expressed in virtually all cells of higher organisms
it is estimated that roughly 25% of all cytoplasmic ATP is hydrolyzed by sodium
pumps
depending on cell type, there are between 800,000 and 30 million pumps on
the surface of cells
several types of heart failure are associated with significant reductions in
myocardial concentration of Na + -K + -ATPase
5

extracellular
intracellular
Na + , K + - ATPase Pump
(Sodium Pump)
composed of two subunits
alpha subunit (~113 kD): it binds ATP and
both sodium and potassium ions, and
contains the phosphorylation site
beta subunit (~35 kDa glycoprotein):
absolutely necessary for activity of the
complex
several isoforms of both alpha and beta
subunits have been identified
Action Potential
Action Potential
Jens Christian Skou
(danish)
1997: Nobel prize
Na +
+ + + + + + + + + + + + + + + + + - - - - - - - + + + + + + + + + + + +
- - - - - - - - - - - - - - - - - - + + + + + + + - - - - - - - - - - - -
K +
Outside
Inside
Na + , K + - ATPase Pump
Na +
Outside
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
3 Na+
2 K +
Na + , K + - ATPase Pump
A -
K + Cl- 142 mEq/L
4 mEq/L
K +
140 mEq/L
Cl -
Action Potential
K + Cl -
Na Inside
+
14 mEq/L
Na +
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
K +
Outside
Na
Inside
+
Cl- A- Action Potential
Na +
+ + + + + + + + + + + + + + + + + - - - - - - - + + + + + + + + + + + +
- - - - - - - - - - - - - - - - - - + + + + + + + - - - - - - - - - - - -
K +
Outside
3 Na
Inside
+
2 K +
Na + , K + - ATPase Pump
6

Course of the Action Potential
• The action potential begins with a partial depolarization (e.g.
from firing of another neuron ) [A].
• When the excitation threshold is reached there is a sudden
large depolarization [B].
• This is followed rapidly by repolarization [C] and a brief
hyperpolarization [D].
• There is a refractory period immediately after the action
potential where no depolarization can occur [E]
Membrane
potential
(mV)"
+40"
0"
-70"
[A]"
[B]"
[C]"
[E]
0" 1" 2" 3"
[D]" excitation threshold!
Time (msec)"
7