Topics

1. Introduction
2. Energy and thermodynamics
3. Feeding and digestion
4. Ionic gradient, electrical potential
5. Electrical signals and neurons
6. Cytoskeletons, motor proteins and muscle
7. Heat production and body temperature

Learning
Doing (experience)
Thinking
(reflection)
Information
Changes in
knowledge, skills,
attitude, value,
belief, etc.
Transport
Diffusion
http://hyperphysics.phy-astr.gsu.edu/hbase/Kinetic/diffus.html
http://highered.mcgraw-
hill.com/sites/0072495855/student_view0/chapter2/animation__how_diffusion
_works.html
Facilitated diffusion
http://highered.mcgraw-
hill.com/sites/0072495855/student_view0/chapter2/animation__how_facilitate
d_diffusion_works.html
Transport across cell membrane (active transport)
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/D/Diffusion.html
Active transport animation
http://www.northland.cc.mn.us/biology/BIOLOGY1111/animations/active1.swf


http://highered.mcgraw-
hill.com/sites/0072495855/student_view0/chapter2/animation__how_diffusion
_works.html

http://highered.mcgraw-
hill.com/sites/0072495855/student_view0/chapter2/animation__how_osmosis
_works.html

http://highered.mcgraw-
hill.com/sites/0072495855/student_view0/chapter2/animation__how_the_sodi
um_potassium_pump_works.html

http://hyperphysics.phy-astr.gsu.edu/hbase/Kinetic/diffus.html

http://www.youtube.com/watch?v=ULR79TiUj80
Chemical composition of some purified membranes
(in percentages)
Membrane Protein Lipid Carbohydrate
Myelin 18 79 3

Plasma membrane
Human erythrocyte 49 43 8
Mouse liver 44 52 4
Amoeba 54 42 4
Halobacterium
purple membrane 75 25 0
Mitochondrial
inner membrane 76 24 0

Chloroplast
Spinach lamellae 70 30 0
Why was phospholipids chosen as the basic
component of biomembranes during
evolution?
A) Water has very high surface tension (70
dynes/cm).
Therefore it is impossible to use pure water to
form closed structures.
Phospholipid can lower the surface tension of
water to 1-2 dynes/cm so that it can be spread
out naturally.

http://www2.hawaii.edu/~yzuo/research1-surfactant.html

B) A lipid bilayer sheet would be an unstable
structure if it had a free edge at which the
hydrophobic region of the bilayer were in
contact with water.
Hence, phospholipid membranes
spontaneously seal to form closed structures.

Learning
Doing (experience)
Thinking
(reflection)
Information
Changes in
knowledge, skills,
attitude, value,
belief, etc.
Learning = new information + new
skills + new experience
Learning =making new connections
between information, skills and
experience
Learning = un-learn + re-learn
Topics
1. Introduction
2. Energy and thermodynamics
3. Feeding and digestion
4. Ionic gradient, electrical potential
5. Electrical signals and neurons
6. Cytoskeletons, motor proteins and muscle
7. Heat production and body temperature

K
+
K
+
Na
+
Na
+
Cl
-
Cl
-
P
-
1. Selective permeable to various ions and solutes
2. Thin and can separate charge (behaves as a
capacitor)
Mg
++
+
+
+
+
+
+
+
_
_
_
_
_
_
_
_ +
Diffusion is the movement of
molecules from a region of
higher concentration to a
region of lower
concentration.
Prior knowledge:
Diffusion is the movement of
molecules from a region of
higher concentration to a
region of lower
concentration = No diffusion
when there is no
concentration gradient
Rate of movement of
individual molecules
(distance/time)

Slow
Rate of movement of
individual molecules
(distance/time)

The same
Slow
Rate of movement of
individual molecules
(distance/time)

Not so slow
What is the meaning of Diffusion?
Diffusion is a kinetic property of molecules
related to temperature
i.e., a type of thermal motion.
Diffusion velocity of individual molecules

distance
time
disregarding the direction
is o
1
/
\ m
(Grahams law)
o Temp (
o
K)
XXX not o concentration
Rate of movement of
individual molecules
(distance/time)
Effects of
concentration
gradient
(no change)
But, how about #molecules/time through
the imaginary barrier? (Low flux )
Rate of movement of
individual molecules
(distance/time)
Effects of
concentration
gradient
(no change)
But, how about #molecules/time through
the imaginary barrier? (Higher flux)
1)Why is there the movement of individual
molecules at a certain temperature?

Because of heat - kinetic theory

2)Why is there the net movement of molecules
in bulk across an imaginary or physical barrier?

Because of the presence of a chemical
potential gradient.

(
Flux =
mole
Area Time
)
Rate of movement of
individual molecules
(distance/time)
In equilibrium
with the
surroundings
(Will molecules
stop moving?)
NO!!! But, net flux =0 Net flux would stop
Will there be movement of
solute molecule from a
region of high concentration
to low concentration in
water at -80
o
C, at -200
o
C?
Diffusion is the
movement of
molecules from a
region of higher
concentration to a
region of lower
concentration.
This definition of diffusion conveys a wrong
meaning of diffusion!!!
So, what do you think about
the definition below?
Molecules move from a region
of higher concentration to a
region of lower concentration
by diffusion.
Learning
Doing (experience)
Thinking
(reflection)
Information
Changes in
knowledge, skills,
attitude, value,
belief, etc.
Todays task:
Can you define diffusion
using your own words?
A Question for thought:
Is it a good idea to use
perfume to explain
diffusion?
Can living systems survive by depending
on only diffusion of substances across
their biomembranes?
NO !!
But why?
1) Not all substances can dissolve in lipids.

2) Diffusion cannot maintain the gradients
required for the living system to function
Solution??
Facilitated diffusion

Active Transport
Transport
Diffusion
http://hyperphysics.phy-astr.gsu.edu/hbase/Kinetic/diffus.html
http://highered.mcgraw-
hill.com/sites/0072495855/student_view0/chapter2/animation__how_diffusion
_works.html
Facilitated diffusion
http://highered.mcgraw-
hill.com/sites/0072495855/student_view0/chapter2/animation__how_facilitate
d_diffusion_works.html
Transport across cell membrane (active transport)
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/D/Diffusion.html
Active transport animation
http://www.northland.cc.mn.us/biology/BIOLOGY1111/animations/active1.swf


Active Transport :
a process in which the system gains free
energy (cellular energy is involved)
C
1
C
2

AG = RT In
C
2
C
1
0.01M
1mole
0.1M
AG = RT In
0.1
0.01
= 1.98 x 293 x 2.303 x log 10

= 1340 cal

downhill
uphill
Active Transport process :
Final state
High electrochemical
potential
Initial state
Low electrochemical
potential
AG = +
The mechanism involved does not define the process!!!
Heres where the confusion comes in !!!
Solar energy/light
Chemical potential energy e.g. Na+ or K+ gradient
Chemical energy, ATP
Chemical energy, e.g. carbohydrate
Electrical energy, e.g. membrane potential
Heat
Heat
Heat
Heat
Solar energy/light
Chemical potential energy e.g. Na+ or K+ gradient
Chemical energy, ATP
Chemical energy, e.g. carbohydrate
Heat
Heat
Heat
Is it true that only
processes which involve
the movement of a
substance against its
chemical and/or electrical
potential gradient(s) are
regarded as active
transport processes?
Yes.
K
+
K
+
Na
+
Na
+
Cl
-
Cl
-
P
-
An important function of the plasma membrane is to
maintain an ionic composition in the cytosol very different
from that of the surrounding fluid.
small subunit
(55,000)
2 sites for K
+
and one for ouabain
3 sites for Na
+

ADP + Pi
ATP
Catalytic site of ATP
large subunit
(120,000)
oligosaccharide
K
+

Na
+

K
+

Na
+

NKA in action
http://www.youtube.com/watch?v=bGJIvEb6x6w&NR=1
Intracellular
Extracellular
Na
+
15 mM
K
+
150 mM
Na
+
140 mM
K
+
4 mM
ATP
ADP + Pi
3 Na
+
2 K
+
The primary active transport of sodium and potassium ions
in opposite directions by the Na,K-ATPase in plasma
membranes is responsible for the low sodium and high
potassium intracellular concentrations. For each ATP
hydrolysed, 3 sodium ions are moved out of a cell and 2
potassium ions are moved in.
Active Transport
1) Active Transport process
2) Active Transport mechanisms

e.g. i) 1
0
active pump
(Na
+
, K
+
- ATPase, Ca
2+
- ATPase)
ii) 2
0
active pump
(Glucose, Na
+
- Cotransport Mechanism)
Here four thermodynamic processes are involved.
a) K
+
transport
b) Na
+
transport
c) ATP hydrolysis
d) Overall coupled transport
Other ATPase pumps
e.g.
1) Ca
2+
- ATPase pumps calcium ions out of the
cytoplasm, maintaining a low intracellular
concentration.
2) A proton pump causes acidification of the
stomach contents.
Solar energy/light
Chemical potential energy e.g. Na+ or K+ gradient
Chemical energy, ATP
Chemical energy, e.g. carbohydrate
Electrical energy, e.g. membrane potential
Heat
Heat
Heat
Heat
pure artificial phospholipid bilayer
Water
H
2
O
Gases
CO
2
N
2
O
2
Small uncharged
polar molecules
Large uncharged
polar molecules
Urea
Ethanol
Glucose
Ions
K
+
, Na
+
Mg
++
, Ca
++
CI
-
, HCO
3
-
, HPO
4
2-
Charged
polar
molecules
Amino
acids
ATP
4-

G6-P
2-
X
X
X
Is facilitated diffusion of
charged ions or molecules
(e.g. K
+
, Na
+
etc.) through the
biomembrane the same as
facilitated diffusion of
uncharged molecules (e.g.
glucose) or simple diffusion
of lipid soluble molecules
through the lipid bilayer?
A measure of hydrophobicity is the partition coefficient,
the equilibrium constant for partition of the molecule
between oil and water.





In relation to this, biomembrane can be described as
differentially or selectively permeable.


Partition coefficient
amount dissolving in oil
amount dissolving in water
Certain membrane proteins speed up the
movement of specific ions or molecules
across the membrane - facilitated
diffusion - without using cellular energy

1. The flux is far greater than would be
expected from a simple diffusion model
based on hydrophobicity and Ficks law.

2. The process is substrate specific;
each protein transport only a single species
of ion or molecule, of a single group of closely
relate molecules.
3. There exists a maximal rate of transport.

4. There exists the pH and temperature optima.
Solar energy/light
Chemical potential energy e.g. Na+ or K+ gradient
Chemical energy, ATP
Chemical energy, e.g. carbohydrate
Electrical energy, e.g. membrane potential
Heat
Heat
Heat
Heat
Aquaporin
Is facilitated diffusion of
charged ions or molecules
(e.g. K
+
, Na
+
etc.) through the
biomembrane the same as
facilitated diffusion of
uncharged molecules (e.g.
glucose) or simple diffusion
of lipid soluble molecules
through the lipid bilayer?
No,
they are not quite
the same.
1. For uncharged molecules or lipid
soluble molecules, the only 2 types of
energy involved are heat and chemical
potential.
For charged molecules, electrical
potential is also involved.
Na
+
Cl
-
What is the speed of ions in motion?
Can you call it diffusion? No!!
A
Na
+
Cl
-
+
-
Current
2. For uncharged molecules, C
1
= C
2
at
equilibrium,
i.e. AC = 0.
However, for charged molecules,
AC = 0 at equilibrium.
Also, AV
1
= 0.

Now equilibrium is achieved between
Chemical potential difference = Electrical
potential difference.
X
X
3. For uncharged molecules, the movement
of individual molecules is due to thermal
motion, or heat.
Such diffusion velocity (distance / time) is
relatively slow.
For charged molecules, the movement of
individual molecules can be affected by
an electrical potential and the velocity can
be very fast.
Such a movement = diffusion.
X
Na
+
Cl
-
What is the speed of ions in motion?
Can you call it diffusion? No!!
A
Na
+
Cl
-
+
-
Current
Topics
1. Introduction
2. Energy and thermodynamics
3. Feeding and digestion
4. Ionic gradient, electrical potential
5. Electrical signals and neurons
6. Cytoskeletons, motor proteins and muscle
7. Heat production and body temperature

+ + + + +
+
+
+
+
+
+
+
+ + + + +
+
+
+
+
+
+
+
-
-
-
-
-
-
-
K
+
140 7 (mM)
Na
+
12 110 (mM)
Cl
-
10 117 (mM)

P
-
-
-
-
-
-
-
-
Cell
-
+
Anion
Cation
V
Vmi-o = -60 mV
- - - - -
- - - - -
The separation of electric charge across a plasma membrane
(membrane potential) provides the electric force that drives
positive ions into a cell and negative ions out of a cell.
Na
+
Cl
-
What is the speed of ions in motion?
Can you call it diffusion? No!!
A
Na
+
Cl
-
+
-
Current
Membrane voltage
Membrane potential
http://www.cvphysiology.com/Arrhythmias/A007.htm
Membrane potential concept-Rice U
http://www.ruf.rice.edu/~bioslabs/bios415/mempot1.htm



Membrane resistance
Membranes act as barriers to the free diffusion
of ions.
Lipid bilayers would have very high resistance
(low conductance) to ions.
But, resistance to a specific ion can be lowered
by the opening of protein channels which
facilitate the movement of this specific ion.
Resistance =
1
conductance
Variable resistor
Outside Inside
[Cl
-
] [K
+
]

[K
+
] [Cl
-
]

Variable resistor
(K
+
channel)
K
+
K
+
K
+
K
+
K
+
K
+
capacitor
Cl
-
Cl
-
Cl
-
Membrane capacitance
Because they are very thin (100 A) and are
virtually impermeable to ions over most of
their surface areas,
biomembranes are able to violate the
principle of electroneutrality at the
microscopic level.
The ability of membranes to accumulate and
separate charges gives rise to the electrical
property of membrane capacitance.
( 1 -3 farad / cm
2
)
Different types of capacitors
Outside Inside
[Cl
-
] [K
+
]

[K
+
] [Cl
-
]

Variable resistor
(K
+
channel)
K
+
K
+
K
+
K
+
K
+
K
+
capacitor
Cl
-
Cl
-
Cl
-
Outside Inside
[Cl
-
] [K
+
]

[K
+
] [Cl
-
]

Variable resistor
(K
+
channel)
K
+
K
+
K
+
K
+
K
+
K
+
capacitor
Cl
-
Cl
-
Cl
-
C
k
< C
k
(Chemical potential)
V
out
> V
in
(Electrical potential)
Charges (K
+
and Cl
-
) are separated across
biomembranes at microscopic level.
V C
You have learned from physics that you
can equate gravitational potential
energy and kinetic energy through :
mgh = mv
2
.
Similarly, you can equate chemical
potential energy and electrical energy
through the Nernst Equation:
E
i-o
=
RT
ZF
ln
C
0
C
i
E
Ki-o
=
RT
ZF
ln
[7]

[140]

= - 75 mV
At equilibrium, when there is no net flow of K
+

across the membrane,

V
m
= E
K

After the movement of K
+
across the
membrane through the K
+
channels, the
changes in K
+
concentrations in both sides are
negligible.
Solar energy/light
Chemical potential energy e.g. Na+ or K+ gradient
Chemical energy, ATP
Chemical energy, e.g. carbohydrate
Electrical energy, e.g. membrane potential
Heat
Heat
Heat
Heat
Summary on relationship between NKA and membrane potential
http://www.youtube.com/watch?v=iA-Gdkje6pg

Recall from Physics:
q = C.V

If you have an air compressor with the tank pressure at
100PSI it will be filled with twice as many air molecules than
if its pressure was at 50PSI.

Looking at it another way, if you have an air compressor with
a 5 gallon tank and another one with a 10 gallon tank and
they're both filled to 100PSI, the 10 gallon tank will have
twice as much air in it as the 5 gallon one.

C is analogous to the capacity of the tank,
q is analogous to the quantity of air molecules it's
holding,
V is analogous to the tank pressure.


Recall from Physics:

q = C.V
where q = charges need to be separated and
accumulated across the capacitor.

C = capacitance
V = voltage built up across the capacitor

For a biomembrane of 1 f / cm
2
capacitance to build
up a voltage of 60 mV across it, the amount of ions to
be separated is:

q = C.V
= (1 x 10
6
F / cm
2
) . (6 x 10
-2
V)
= 6 x 10
-8
coulombs / cm
2

There are 96,500 coulombs of charge (1
faraday) in mole of a monovalent ion.
Hence,
= 6 x 10
-8
coulombs /cm
2
96,500 coulombs / mole ion
= 6 x 10
13
mole ion / cm
2
Does it mean that Na
+
and Cl
-
are
perfectly impermeable and do not
contribute to Vm?

Note that 75mV (E
K
) is close to 60mV
(Vm) but not exactly the same.

The relative permeabilities of K
+
, Na
+

and Cl
-
through biomembranes are
1 : 0.04 : 0.45
After knowing these. Dr Goldman derived
another equation:
Vm =
RT
(+1)F
ln
P
k
[K]
0
+ P
Na
[Na]
0
+ P
C1
[Cl]
i
P
k
[K]
i
+ P
Na
[Na]
i
+ P
C1
[Cl]
0
Substituting all the values into the
equation:
Vm
i-o
= 58 log
10
60
654
= -60.1 mV
+55
-60
-75
(V
m
-E
Na
)
V
m(i-o)
0
(mV)
(V
m
-E
k
)
E
K
E
Na
Resting memb. potential
Difference is small.Hence,e.m.f
.k
is
small. Though K
+
channels are open,
net flux of K
+
is small as it is close to
equilibrium.
Difference is large. Hence, e.m.f.
Na
is
large. Though e.m.f.
Na
is large, net
flux of Na
+
is small because most Na
+

channels are closed.
Formation of action potential
Can the movement of Na
+
in this case be
regarded as diffusion?

No!!!
+ + + + + + + + + + + + +
- - - - - - - - - - - - -
-
+
Transmission of
impulse
Na
+
Na
+
Axon
facilitated diffusion
Conclusion
1. Protein channels in biomembranes behave as
variable resistors
(e.g. to K
+
, Na
+
).

2. Phospholipid regions of biomembranes act as
capacitors.
Usually capacitance is small (1 3 f / cm
2
).
3. The concentration gradients of various ions
(Na
+
, K
+
, Cl
-
) existing across the membrane
behaves as ionic batteries.
Energy is stored in the gradient as chemical
potential.

4. At rest, biomembranes are selectively
permeable to K
+
.
5. Movement of K
+
down its chemical potential ( i
to o) gradient leads to a separation of charge
and an electrical potential gradient is built up
across the biomembrane.

6. Chemical potential can be equated to electrical
potential by the Nernst Equation.
7. After the movement of K
+
, the concentrations
of K
+
in the 2 compartments are insignificantly
affected.
8. At equilibrium, Vm = E
k
.
9. At resting, Vm is slightly more positive than E
k
.
10. The polarity of Vm existing across a
membrane can be reverted by a change in the
selective permeability of the membrane.

11. At resting, although K
+
channels are open,
e.m.f. is small as Vm ~ E
k
.
12. However, at resting, e.m.f.
Na+
is large as Vm is
very different from E
Na
.
Though e.m.f.
Na
is large, movement of Na
+
is
negligible because most Na
+
channels are
closed.

How does the movement of charged molecules differ from
uncharged molecules across an ion-selective membrane?
+
+
Mind Maps
Summarize information, act as mnemonics
Quickly identify and understand the structure of a
subject
Appreciate how pieces of information fit together
Provide a structure and encourages creative
problem solving
Hold information in a format that the human mind
will find easy to remember and quick to review
1. Use single words or simple phrases.
2. Position the main idea/problem in the center.
3. Use lot of space so that things can be added
on later.
4. Use color to separate different ideas;
personalize the map.
5. Look for relationships; cross-link with lines
and arrows; label the lines where applicable.
6. Create sub-center for sub-themes.
Please submit your mind map to IVLE, if your
wish (not compulsory, no marking/grading),
so that you can learn from each other.

Please submit in Word format, and state your
name and email address.

GENERAL PHYSIOLOGY General
information and submission folder AY12-
13(I)

End