Some Functions of Some Integral Membrane proteins

http://www.bristol.ac.uk/phys-pharm/media/teaching/ (from the “Chemistry of the cell”)

Physiology of the Cell Anchoring/connecting Receptor – detects chemical signals A channel (leak)

Membrane
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 In extracellular
fluid
40

20

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): If the membrane was freely permeable to these molecules…

Intracellular fluid Extracellular fluid

~2/3 or ~65% ~1/3 or ~35%

Interstitial Plasma of
fluid the blood
~28% of TBW ~7% of TBW
(~80% of ECF) (~20% of ECF)

The first message: the cell membrane is NOT freely

permeable to polarised/ionised/hydrophilic
molecules

1
 Polar molecules and ions Small, uncharged molecules Chemical vs Electrical Driving Force
cannot freely pass through pass through the membrane
the membrane O2 Ethanol
H+ CO2 Glycerol
Glucose
Na+ N2 Steroids
Amino Acids
Cl-
Ca2+

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 Electrical driving force

K+ 140 4
Na+ 15 145
Mg2+ 0.8 1.5
Ca2+ 0.001 1.8
_
Cl- 4 115 _ + +
_ +
+
+
HCO3- 10 25 _ +
_ +
Inorganic P- - 40 2 _ + +
+
+
_+ +
_
Amino acids +/- 8 2 _ + +
_ +
+
Glucose +/- 1 5.8 _ + +
_ +
+
ATP +/- 4 0 _
_ + +
Protein +/- 4 0.2 _ + +
_ +
_ +
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. ONLY applies to charged particles, such as ions

Forces which determine the direction of transport Chemical and Electrical Driving Forces may combine
across the membrane to create the Electrochemical Driving Force
Passive vs active transport + _+
+ _ _ + _+
+
4mM
K+
Passive Active
_+ Chemical driving force
- along the concentration - against the concentration +_ +
+ +
gradient and using the energy gradient + _
of this gradient - uses energy supplied by the + _ + + +
cell to special proteins called
+ _
_ + 140 mM +
PUMPS + +
+
_ _ Electrical driving force
+ +
CO2 + _ + + +
_
+ What will happen if the potential of
+ _ -70
_ _mV
_
this membrane decreases to -10 mV?
+ + Chemical driving force
+ +

These guys are

called pumps! Electrical driving force

2
 Chemical driving force
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 Electrical driving force _
and the force generated by electric field). _
_ +
+
+ +
+
_ +
_
_ + +
+
_ +
_+
_ + +
_
+
+
+
_ +
+
_
_ +
Net flux + +
_ + +
_ +
+
+

V
Equilibrim potential (or reversal potential)

Chemical driving force The Reversal Potential

(same as equilibrium potential):
Potential of the membrane at which the
electrical driving force is exactly equal the
Electrical driving force _
_ +
chemical driving force and therefore
THE NET FLUX of charged particles (of
+
+
+
_ +
one particular kind) is NIL.
_ + +
+
_+
+ +
_
+
+
+
_ +
+
_ +
+

_ + Net flux +
_ +
+

Chemical driving force

The reversal (equilibrium) potential
can be calculated using Nernst equation:

Eion = 61.5mV Log (C /C )

Electrical driving force 10 out in
Z
_
_ +
+
_ +
++
_
_ +
+
_
_ + + +
+
_
_+
+
_
_
_
_ + ++
_
_
+
++ IMPORTANT:
_ +
+
_ +
+
_ +
+ 61.5 is a calculated constant derived from universal gas constant, the temperature (37oC)
_
_
+

_ + Net flux + 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
Exercise
or CO2
-Chapter 6 in Boron – Boulpaep Textbook

Be prepared to calculate the reversal potentials of the

ions. O2
Also read about Goldman Equation which describes
membrane potential when more than one ion is involved: Net
CO2

Flux
PK[Ko] + PNa[Nao] + PCl[Cli]
Vm = 61.5 * Log10
PK[Ki] + PNa[Nai] + PCl[Clo]
Concentration

But for glucose…

Mechanisms of Passive
Transport
Transport Net
Flux
Passive Active
Concentration
2. Facilitated 3. Diffusion
1. Simple
Diffusion through Ion
Diffusion
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)
For glucose the maximum rate can be ~ 10.000 molecules per second

Net
Flux Factors affecting the speed of facilitated
diffusion:
1. The magnitude of the driving force
Concentration 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 – Cl-
3. 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. The magnitude of the electro-chemical driving force
2. The transport rate of the individual channels (conductance)
3. The number of available channels
4. State of channels (open/close) in case they are gated (ADD
TO YOUR HANDOUTS!!!)

Passive transp.flv

Active transport
IN OUT Key features:
K+ 140 4 1. Occurs irrespective of the chemical
and/or electrical gradient
Na+ 15 145 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!