St. Luke’s College of Medicine – William H.

Quasha Memorial
PHYSIOLOGY BLOCK 1

Lecture: 2- Membrane Transport Date: 29/07/2015

Lecturer: Antonio C. Pasco III, MD, FPSP Trans Team: Capinpin, Capistrano, Caseñas, Cayetano
______________________

Topic Outline o Diameter of channel – larger diameter will allow

I. Cell Membrane
II. Passive Transport
A. Simple Diffusion
B. Facilitated Diffusion
C. Factors Affecting the Rate of Diffusion
D. Osmosis
III. Active Transport
A. Primary Active Transport
B. Secondary Active Transport
I. Cell Membrane
 Best represented by the Fluid Mosaic Model developed by
Singer and Nicolson
 Selectively permeable – allows transport of certain
molecules or ions by either passive or active transport
o Membrane is comprised of a lipid bilayer (with hydrophilic
heads and hydrophobic tails) where few substances can
penetrate and diffuse directly through the lipid substance
o Transport proteins– protein structures that interrupt the
continuity of the lipid bilayer and provide alternative
pathways through the cell membrane
o Channel proteins – aqueous spaces all the way through
the membrane that allow free movement of water and
selected ions or molecules
o Carrier proteins–binds to molecules or ions to be
transported; conformational changes in the protein
molecule then move the substances through the
interstices of the protein to the other side of the membrane
more molecules to pass through
o Shape – only allows molecules conforming to the
shape of the channel to pass through
o Nature of electrical charges/chemical bonds lining
the surface
 With gate-like extensions that open or close the
channels by undergoing conformational change
(triggered by change in electrical potential across the
membrane or binding of a substance to the protein)
o Voltage gating – mainly relies on voltage
difference between ECF and ICF
Ex: Electric potential (voltage difference) causes
the outside sodium gate to open and allow passage
of Na+
Figure 2. Example of a voltage gated protein channel.
o Chemical or ligand gating - Some protein channel
gates are opened by the binding of a chemical
substance (a ligand) with the protein; this causes a
conformational change in the protein molecule that
opens or closes the gate.
Ex: Acetylcholine (Ach) triggers a conformational
change in the Ach-gated channel allowing the
passage of Na+

Figure 1. Fluid Mosaic model of the cell membrane.

II. Passive Transport

“

 “Downhill movement” of molecules/ions along a

concentration/electrical/pressure gradient (from higher to
lower) across the semi-permeable membrane
 Results in uniform distribution of molecules
o No net movement: IN = OUT
o Equilibrium is attained
 Utilizes energy from kinetic motion
 Three types:
1. Simple Diffusion (Solutes)
2. Facilitated Diffusion
3. Osmosis (Solvent)
A. Simple Diffusion
 Movement of solutes from an area of higher concentration
to lower concentration through:
1. The lipid bilayer
- Permeable only to lipid-soluble substances; rate of
diffusion depends on lipid solubility of the substance
- Oxygen, nitrogen, carbon dioxide, and alcohols can easily
pass through due to high lipid solubility
2. Protein channels
- Where most lipid-insoluble substances pass through
o Ex: water passes through aquaporins, a protein channel
 Are also selectively permeable depending on:
Figure 3. Example of a protein channel opened through binding of
a ligand.
B. Facilitated Diffusion
 Also known as carrier mediated diffusion, because a
substance transported this way diffuses through the
membrane with the aid of a specific carrier protein that
induces a conformational change in order to pass through
 Still a downhill movement(like simple diffusion)
 It is more rapid than simple diffusion
 Does not require additional input of energy, therefore it is
not depressed by metabolic inhibitors (which inhibit the
production of ATP)
 Also acts to equalize concentration on both sides of the
membrane
 Follows saturation kinetics: the rate of diffusion
approaches a maximum (Vmax)

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 PHYSIOLOGY
Figure 4. Effect of concentration of a substance on rate of
diffusion through a membrane by simple diffusion and facilitated
diffusion. This shows that facilitated diffusion approaches a
maximum rate called Vmax.
Figure 5. Postulated mechanism for facilitated diffusion.
 Examples of facilitated diffusion:
- Facilitated diffusion of glucose
- Facilitated diffusion of amino acids
C. Factors Affecting the Rate of Diffusion
1. Gradients
a. Concentration- movement of molecules from a higher
concentration to a lower concentration (Figure 6-A)
b. Electrical
- The electrical charges of the ions cause them to move
through the membrane even though no concentration
gradient exists
- Negative ions will move to the positive side of the
membrane (Figure 6-B)and vice versa
- Nernst Equation
o Computes for the electrical potential that will balance
the concentration gradient (Nernst Potential)
𝐶1
𝐸𝑀𝐹(𝑖𝑛𝑚𝑖𝑙𝑙𝑖𝑣𝑜𝑙𝑡𝑠) = ±61 𝑙𝑜𝑔
𝐶2
o EMF is the electromotive force (voltage) between the
two sides of the membrane; C1 is the concentration
on the 1st side; C2 is the concentration on the 2nd side
c. Pressure Gradient
- Movement of molecules from the side of higher pressure
to lower pressure
- More molecules strike the membrane at the side with
higher pressure causing an increase in energy
available; this results to a net movement of molecules
2. Range of Diffusion (distance)
- Molecules take 1 millisecond to diffuse 1 micrometer
- Time of diffusion increases with the square of distance
- A 10 times increase in distance increases diffusion time
by 100 times
3. Thickness of Membrane
- Inversely proportional to the rate of diffusion
4. Temperature
- Directly proportional to the rate of diffusion
Diffusion Coefficient (aka Stokes-Einstein Equation)
kT
D=
6πη𝑟
 It is directly proportional to temperature (T);and
inversely proportional to the radius/size of the diffusing
particle (r) and viscosity (η) of medium
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BLOCK 1
 The higher the temperature, the diffusion coefficient
increases (diffusion is faster)
 The more viscous the medium, the diffusion coefficient
decreases
“You just need to understand the formula more than
memorizing the formula for computation’s sake.”
– Dr. Pasco
Fick’s First Law of Diffusion
Δc
J = −DA
Δx
 Directly proportional to the driving force (concentration
difference: Δc), diffusion coefficient (D), and the surface
area of diffusion (A)
 Inversely proportional to membrane thickness (Δx)
 Especially important in the diffusion of gases: oxygen
and carbon dioxide in the respiratory system
Figure 6. Effect of concentration difference (A), electrical potential
difference (B), and pressure difference (C) causes the diffusion of
molecules and ions through a membrane.
5. Size of Molecules
6. Permeability and Solubility
- Lipid solubility
 Olive oil/ water partition coefficient
- High water permeability
 Pass between adjacent phospholipid molecules and
through aquaporins
 Permeability decreases as size of uncharged water
soluble molecules increases (mw>200)
- Ions usually cannot pass membranes and use ion
channels
- Depends on channel diameter, inner surfaces charge,
size of ions and tendency of ions to gather water
molecules (more hydrated molecules that do not easily
dissociate with water are harder to pass through the ion
channels)
D.Osmosis
 Process of net diffusion of water across a semi-permeable
membrane (permeable to water but not the solute) caused
by concentration difference of the solution
 Higher water concentration (lower solute
concentration)lower water concentration (higher solute
concentration)
Figure 7. Osmosis from the left compartment to the right.
Effect of tonic solutions on cell volume
 Sodium chloride solution of 154 mM or 0.9% (308 Osm/L) is
isotonic
 PHYSIOLOGY BLOCK 1

Primary Active Transport of Calcium Ions

- Calcium ions are normally maintained at extremely low
concentrations in the ICF by two calcium pumps
 In the cell membrane, which pumps calcium out of the
cell
 Another pumps calcium into the intracellular vesicular
organelles of the cell (ex. sarcoplasmic reticulum of
muscle cells, mitochondria)
- Basic process similar to sodium-potassium pump with a
protein that has a specific binding site for calcium (instead
of for sodium)
- Occurs in the muscle, uses action potential

Figure 8. Effect of Tonicity on RBCs.

III. Active Transport

 “Uphill transport” where the cell membrane moves
molecules or ions against a concentration gradient
 Occurs when a large concentration of substance is required
in the intracellular fluid even though the extracellular fluid
contains a small concentration
 Requires additional source of energy (ATP), thus it may
be inhibited by substances that interfere with energy
Figure 10. Calcium Pump.
metabolism
 Occurs with the help of carrier proteins Primary Active Transport of Hydrogen Ions
 Some examples of substances that are actively transported - Important in the gastric glands of the stomach and late
through cell membranes: sodium ions, potassium ions, distal tubules and cortical collecting ducts of the kidneys
calcium ions, hydrogen ions, chloride ions, urate ions, most - Gastric glands: parietal cells use active transport of
amino acids hydrogen to secrete HCl in the stomach
- Renal Tubules: intercalated cells secrete hydrogen ions
A. Primary Active Transport from the blood into the urine for elimination(to maintain
 Uses energy derived directly from breakdown of adenosine acid-base homeostasis)
triphosphate (ATP) or of some other high-energy phosphate
compound B. Secondary Active Transport
 Examples:  Uses energy derived secondarily from stored energy in the
Sodium-Potassium Pump form of ionic concentration differences created by primary
- Transport process that pumps sodium ions out of the cell active transport
and potassium ions from the outside to the inside of the  Example: The sodium gradient, as result of the sodium-
cell potassium pump, will result in sodium attempting to diffuse
- Maintains sodium and potassium concentration inside the cell. In the process, it can pull other substances
differences across the cell membrane along (co-transport) or in exchange with itself (counter-
- Basis of nerve function transport)
- How it works:
1. Cytoplasmic Na+ binds to the Na+-K+ pump.
2. Na+ binding stimulates phosphorylation by ATP.
3. Phosphorylation causes the protein to change its
conformation, expelling Na+ into the outside.
4. Extracellular K+ binds to the protein, triggering the
release of the phosphate group.
5. Loss of the phosphate group restores the protein to its
original conformation.
6. K+ is released and the Na+ sites are receptive again.

Figure 11. Postulated mechanism for sodium co-transport of

glucose.
1 2

6 3

Figure 12. Sodium counter-transport of calcium and hydrogen

ions.
5 4

Figure 9. Sodium-Potassium Pump (note: 3 Na+ sites and 2 K+

sites).

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 PHYSIOLOGY BLOCK 1

IV. Review of Concepts

1. Predict a possible effect of the following conditions:
 Giving of a voltage gated sodium channel blocker.
 A newborn infant without any physical defects but suffers
from glucose-1 transporter deficiency in the brain.

2. Clinical situation:
A patient was brought to the ER because of drowning. On
examination, there is accumulation of fluid in the alveolar
spaces in the pulmonary interstitium
 Explain briefly why this patient will present with hypoxia
and hypercapnia.
 You decided to hook the patient to an oxygen tank. Give a
plausible explanation why.

3. Characterize simple diffusion and facilitated diffusion as to:

 Goal
 Movement of molecules
 Energy used
 Manner of transport

4. How do the following factors affect the rate of diffusion?

 Gradient
 Distance
 Temperature
 Thickness of the membrane
 Viscosity of the medium

5. A patient was brought to the ER because of massive

bleeding and hypertension. For lack of available blood you
decided to infuse the patient first with NaCl solution.
What will be the effect of infusing the patient with?
a. 1.0% NaCl solution
b. 0.45% NaCl solution
c. 0.9% NaCl solution

6. What is the effect of the following conditions?

 Giving of metabolic inhibitors
 Inhibition of sodium-potassium pump
 Inhibition of hydrogen pump by drug Omeprazole
 Defect in calcium pump in the skeletal muscles

V. References
 Dr. Pasco’s lecture
 Textbook of Medical Physiology 12th ed. by Guyton
 Figure 8.Effect of Tonicity on RBCs
o URL: http://biology-
forums.com/index.php?action=gallery;sa=view;id=307

VI. QUIZ
1. What is the best representation of the cell membrane?
2. What are the factors that affect the rate of diffusion?
3. What is the relationship between the diffusion coefficient
and temperature? Diffusion coefficient and viscosity of the
medium?
4. What is another name for the equation of the diffusion
coefficient?
5. This type of pump serves as the basis for nerve function.
6. This type of transport requires an additional source of ATP.
7. True or False: In osmosis, water moves through an area of
high solute concentration to an area of low solute
concentration.
8. True or false: If there is an electrical gradient, ions will
move through a membrane only when a concentration
gradient exists to cause movement.
9. True or false: Facilitated diffusion requires a carrier protein
and an additional source of energy.
10. This type of transport uses energy derived from energy
created by primary active transport.

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