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 more molecules to pass through
II. Passive Transport o Shape – only allows molecules conforming to the
A. Simple Diffusion shape of the channel to pass through
B. Facilitated Diffusion o Nature of electrical charges/chemical bonds lining
C. Factors Affecting the Rate of Diffusion the surface
D. Osmosis
 With gate-like extensions that open or close the
III. Active Transport
A. Primary Active Transport channels by undergoing conformational change
B. Secondary Active Transport (triggered by change in electrical potential across the
membrane or binding of a substance to the protein)
I. Cell Membrane o Voltage gating – mainly relies on voltage
difference between ECF and ICF
 Best represented by the Fluid Mosaic Model developed by
Ex: Electric potential (voltage difference) causes
Singer and Nicolson
the outside sodium gate to open and allow passage
 Selectively permeable – allows transport of certain
of Na+
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 Figure 2. Example of a voltage gated protein channel.
selected ions or molecules
o Carrier proteins–binds to molecules or ions to be o Chemical or ligand gating - Some protein channel
transported; conformational changes in the protein gates are opened by the binding of a chemical
molecule then move the substances through the substance (a ligand) with the protein; this causes a
interstices of the protein to the other side of the membrane 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 Figure 3. Example of a protein channel opened through binding of
 Utilizes energy from kinetic motion a ligand.
 Three types:
1. Simple Diffusion (Solutes) B. Facilitated Diffusion
2. Facilitated Diffusion  Also known as carrier mediated diffusion, because a
3. Osmosis (Solvent) substance transported this way diffuses through the
membrane with the aid of a specific carrier protein that
A. Simple Diffusion induces a conformational change in order to pass through
 Movement of solutes from an area of higher concentration  Still a downhill movement(like simple diffusion)
to lower concentration through:  It is more rapid than simple diffusion
1. The lipid bilayer  Does not require additional input of energy, therefore it is
- Permeable only to lipid-soluble substances; rate of not depressed by metabolic inhibitors (which inhibit the
diffusion depends on lipid solubility of the substance production of ATP)
- Oxygen, nitrogen, carbon dioxide, and alcohols can easily  Also acts to equalize concentration on both sides of the
pass through due to high lipid solubility membrane
2. Protein channels  Follows saturation kinetics: the rate of diffusion
- Where most lipid-insoluble substances pass through approaches a maximum (Vmax)
o Ex: water passes through aquaporins, a protein channel
 Are also selectively permeable depending on:

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 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
Figure 4. Effect of concentration of a substance on rate of difference: Δc), diffusion coefficient (D), and the surface
diffusion through a membrane by simple diffusion and facilitated area of diffusion (A)
diffusion. This shows that facilitated diffusion approaches a  Inversely proportional to membrane thickness (Δx)
maximum rate called Vmax.  Especially important in the diffusion of gases: oxygen
and carbon dioxide in the respiratory system

Figure 5. Postulated mechanism for facilitated diffusion.

 Examples of facilitated diffusion:

- Facilitated diffusion of glucose
- Facilitated diffusion of amino acids
Figure 6. Effect of concentration difference (A), electrical potential
C. Factors Affecting the Rate of Diffusion difference (B), and pressure difference (C) causes the diffusion of
1. Gradients molecules and ions through a membrane.
a. Concentration- movement of molecules from a higher
concentration to a lower concentration (Figure 6-A) 5. Size of Molecules
b. Electrical 6. Permeability and Solubility
- The electrical charges of the ions cause them to move - Lipid solubility
through the membrane even though no concentration  Olive oil/ water partition coefficient
gradient exists - High water permeability
 Pass between adjacent phospholipid molecules and
- Negative ions will move to the positive side of the
through aquaporins
membrane (Figure 6-B)and vice versa
 Permeability decreases as size of uncharged water
- Nernst Equation soluble molecules increases (mw>200)
o Computes for the electrical potential that will balance - Ions usually cannot pass membranes and use ion
the concentration gradient (Nernst Potential) channels
𝐶1 - Depends on channel diameter, inner surfaces charge,
𝐸𝑀𝐹(𝑖𝑛𝑚𝑖𝑙𝑙𝑖𝑣𝑜𝑙𝑡𝑠) = ±61 𝑙𝑜𝑔 size of ions and tendency of ions to gather water
𝐶2 molecules (more hydrated molecules that do not easily
o EMF is the electromotive force (voltage) between the dissociate with water are harder to pass through the ion
two sides of the membrane; C1 is the concentration channels)
on the 1st side; C2 is the concentration on the 2nd side
c. Pressure Gradient D.Osmosis
- Movement of molecules from the side of higher pressure  Process of net diffusion of water across a semi-permeable
membrane (permeable to water but not the solute) caused
to lower pressure
by concentration difference of the solution
- More molecules strike the membrane at the side with
 Higher water concentration (lower solute
higher pressure causing an increase in energy concentration)lower water concentration (higher solute
available; this results to a net movement of molecules concentration)
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)

Figure 7. Osmosis from the left compartment to the right.
kT
D= Effect of tonic solutions on cell volume
6πη𝑟
 It is directly proportional to temperature (T);and  Sodium chloride solution of 154 mM or 0.9% (308 Osm/L) is
inversely proportional to the radius/size of the diffusing isotonic
particle (r) and viscosity (η) of medium

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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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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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