Download Physiology of the Cell Membrane Physiology of the Cell Membrane

Some Functions of Some Integral Membrane proteins
(from the “Chemistry of the cell”)
http://www.bristol.ac.uk/phys-pharm/media/teaching/
Physiology of the Cell
Membrane
Anchoring/connecting
Receptor – detects chemical signals
A channel (leak)
Membrane proteins and their roles (channels, transporters, receptors and structural
proteins). Why molecules move across membranes? Basic laws of membrane permeability.
Trans-membrane transport in the cell.
effect
Chemical reactions
Carriers
A gated channel
The main text for this lecture is:
Germann and Stanfield.
Some additions from Vander
and Cooper’s textbooks
Dr. Sergey Kasparov – room E9
Concentration of selected solutes in intracellular
fluid and extracellular fluid in millimols
mM
160
140
120
100
Inside the cell
80
60
40
In extracellular
fluid
20
0
If this was a cell membrane, which part of the Winnie The Pooh
could be expected to be the most hydrophobic?
Total body water ~(60% of body mass):
Intracellular fluid
~2/3 or ~65%
If the membrane was freely permeable to these molecules…
Extracellular fluid
~1/3 or ~35%
Interstitial
fluid
Plasma of
the blood
(~80% of ECF)
(~20% of ECF)
~28% of TBW
~7% of TBW
The first message: the cell membrane is NOT freely
permeable to polarised/ionised/hydrophilic
molecules
1
Polar molecules and ions
Small, uncharged molecules
cannot freely pass through pass through the membrane
the membrane
O2
Glucose
Amino Acids
H+
Na+
ClCa2+
CO2
N2
Chemical vs Electrical Driving Force
Ethanol
Glycerol
Steroids
Uncharged, non-polar molecules can pass through the
membranes because they can temporarily dissolve in
the lipid bi-layer
Chemical driving force
(applies to ANY molecule irrespective of its charge)
IN OUT
K+
Na+
Mg2+
Ca2+
140
15
0.8
0.001
1.5
1.8
4
10
115
25
ClHCO3Inorganic P- -
40
2
Amino acids +/- 8
1
Glucose +/-
2
5.8
ATP +/Protein +/-
0
0.2
4
4
Electrical driving force
4
145
_
_
_
_
_
_
_+
_
_
_
_
_
_
_
_
_
_
The second message: the cell is able to actively move
certain molecules across its membrane.
Proteins and ATP are synthesised inside the cell,
therefore are highly concentrated there.
Forces which determine the direction of transport
across the membrane
Active
- against the concentration
gradient
- uses energy supplied by the
cell to special proteins called
PUMPS
CO2
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
Chemical and Electrical Driving Forces may combine
to create the Electrochemical Driving Force
+ _+
+ _ _ + _+
+_
+ _
_ +
+
_
+ _
+
+
+
+
+
+
140 mM
+
+
+
+
_+
_
+
+
_
+
_
+
_
+
_
+ _ -70
_ _mV
+
+
+ +
These guys are
called pumps!
+
ONLY applies to charged particles, such as ions
Passive vs active transport
Passive
- along the concentration
gradient and using the energy
of this gradient
+
+
+
+
+
K+
4mM
+
Chemical driving force
Electrical driving force
What will happen if the potential of
this membrane decreases to -10 mV?
Chemical driving force
Electrical driving force
2
Conclusion: movement of charged particles
such as ions, across the membrane depends
on electro-chemical driving force (the sum of
the force generated by chemical gradient
and the force generated by electric field).
Chemical driving force
Electrical driving force
_
_
_
_
_
_
_
_+
_
_
_
_
_
_
_
+
+
+
+
+
+
+
+
+
+
Net flux
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
V
Equilibrim potential (or reversal potential)
The Reversal Potential
(same as equilibrium potential):
Potential of the membrane at which the
electrical driving force is exactly equal the
chemical driving force and therefore
THE NET FLUX of charged particles (of
one particular kind) is NIL.
Chemical driving force
Electrical driving force
_
_
_
_
_+
_
_
_
_
_
+
+
+
+
+
+
+
+
+
+
+
Net flux
+
+
+
+
+
+
+
+
+
+
V
Chemical driving force
Electrical driving force
The reversal (equilibrium) potential
can be calculated using Nernst equation:
_
_
_
_
_
_
_
_
+
_
_
_
_
_
_
_
_
_
_
_
_
_
_
Eion =
+
+
+
+
+
+
+
+
+
+
+
+
+
Net flux
+
++
+
+
+
+
++
++
+
+
+
+
+
+
+
V
61.5mV Log (C /C )
out
in
10
Z
IMPORTANT:
61.5 is a calculated constant derived from universal gas constant, the temperature (37oC)
and Faraday electrical constant. For 20oC it is 58.1. For 25oC it is 60. This is why
different textbooks sometimes give you different values (In Vander’s physiology it is 60!).
Z – is a valence of an ion. Remember, for a negative ion it will be negative.
3
You MUST look through the relevant chapters in the
textbooks:
Rest
E.g.:
- Chapter 6 in Vander’s Human Physiology (10th ed)
O2
or
-Chapter 6 in Boron – Boulpaep Textbook
Be prepared to calculate the reversal potentials of the
ions.
Also read about Goldman Equation which describes
membrane potential when more than one ion is involved:
Vm = 61.5 * Log10
Exercise
CO2
PK[Ko] + PNa[Nao] + PCl[Cli]
PK[Ki] + PNa[Nai] + PCl[Clo]
O2
CO2
Net
Flux
Concentration
But for glucose…
Mechanisms of Passive
Transport
Transport
Active
Passive
Net
Flux
Concentration
1. Simple
Diffusion
2. Facilitated
Diffusion
3. Diffusion
through Ion
Channels
Facilitated diffusion
HANDOUTS: PAGE “Transport”
Factors affecting the speed of simple diffusion:
1. The magnitude of the driving force
2. Surface area of the membrane
3. Permeability of the membrane
Fick’s law:
Net flux = P(permeability)  A(area)  (C)
Net
Flux
For glucose the maximum rate can be ~ 10.000 molecules per second
Factors affecting the speed of facilitated
diffusion:
Concentration
1. The magnitude of the driving force
2. Transport rate of the individual carriers
3. The number of available carriers
4
3. Diffusion through Ion Channels
A leak channel
A gated channel
Both leak and gated channels allow movement of molecules
(mainly inorganic ions) down the electrochemical gradient. So,
if the gradient reverses, the ions will flow in the opposite
direction.
1. The channels are aqueous pores through the membrane.
2. The channels are usually quite selective, for example some only
pass Na+, others K+, still others – Cl3. Gated channels may be opened or closed by various factors (for
example electrical potential of the membrane).
The Key Points:
1. Polar & charged molecules cannot freely diffuse through the cell
membrane but use special molecular pathways. Na+ ions are concentrated
in the extracellular space, K+ inside the cells.
2. Small lipid-soluble molecules can enter the cell because they can pass
through the lipid bi-layer.
3. Molecules move down their concentration gradient. Ions in addition move
according to the electrical field. Therefore for ions we need to consider
the electro-chemical gradients.
4. There are “passive” and “active” means of molecular transport across the
membrane. Passive transport uses the energy of chemical (or
electrochemical) gradient. Active transport uses the energy supplied by
the cell and requires specialised proteins called pumps.
5. Simple passive diffusion occurs in non-saturating manner because it does
not involve any special membrane proteins. All other ways of transport
saturate, because the available number of carrier molecules is always
finite.
6. Ion channels may exist in either open or closed conformation, this can be
regulated by various factors, for example electrical potential of the
membrane.
THERE IS A WEB-BASED TUTORIAL FOR YOU ON THIS TOPIC!
READ ABOUT OSMOSIS!
Factors affecting the speed of diffusion
through ion channels:
1.
2.
3.
4.
The magnitude of the electro-chemical driving force
The transport rate of the individual channels (conductance)
The number of available channels
State of channels (open/close) in case they are gated (ADD
TO YOUR HANDOUTS!!!)
Passive transp.flv
Active transport
IN OUT
K+
140
4
Na+
15
145
Key features:
1. Occurs irrespective of the chemical
and/or electrical gradient
2. Requires an extra chemical source of
energy, supplied by the cell. Directly or
indirectly this is ATP
Active transp.flv
These guys are
called pumps!
5