Active transport mechanisms and biological signals - their origin and propagation. Lectures from Biophysics.

1. Juliana Knocikova
Transport mechanisms
and biological signals –
fundamenals of origin
and propagation

2. The nervous system
The nervous system serves three functions
1. Senses changes both in and outside the body (the sensory function)
2. Interprets and explains the changes (the integrative function)
3. Responds to the interpretation by making muscles interact and glands
secrete hormones or other chemicals into the bloodstream (the motor
function). How do nerve impulses start?
Several types of receptors initiate nerve impulses in
senzory neurons as a result of:
• touch
• pressure
• stretching
• sound waves
• motion
Excitable cells – neurons and muscle cells

3. • dendrites – collect and
gather all informations
•Soma – cell body
(contains own DNA) -
decision for action
potential (AP) happend
there, neurotransmitters
are producing there
• axon hillock – point at
which all information are
cumulated and AP is
initiated
• axons – carries all
information down a
neuron and is controlled
by the soma (coated by
myelin layer)
Basic constitution of the nerve cell - neuron
The connection
between neurons –
synapse

4. •Every cell has a resting membrane potential (RMP)
•Intracellular space is negatively charged under comparison with
extracellular space (typically - 40-90 mV)
Resting membrane potential and its level is a result of:
1. Unbalanced distribution of positive and negative ions inside
and outside the cell
2. Semipermeable membrane (different permeability
for different ions)
K : Cl : Na = 100 : 45 : 4
3. Prítomnosti tzv. Sodium-potassium exchange pump
in cell membrane
Basic resting membrane potential (RMP)

5. Neurones send messages electrochemically; this means that chemicals
(ions) transported by the ion channels in the membrane cause an
electrical impulse.
Resting membrane potential
Ion Concentration
inside cell
[mmol.dm-3
]
Concentration
outside cell
[mmol. dm-3
]
K+ 150 2.5
Na+ 15 145
Cl- 9 101
Rest – condition under which the neurone does not send a signal
These ions do not move down
their concentration gradient
K+ ions do not move out of the
neurone due to positive charges
outside the membrane. This
repels the movement of any more
K+ ions out of the cell.
Cl- ions do not move into the cell
because of the negatively
charged protein molecules (that
cannot cross the surface
membrane) repel them.
Ion pumps generates
concentration difference of ions

6. Resting membrane potential
[ ]
[ ]
[ ]
[ ]e
ie
Cl
Cl
iK
K
−
−
+
+
=
Donnan’s balance – conjuction of concentrations related to the anions
and cations on the one side of the membrane is the same as on the other
side of the membrane
[ ]eK +
[ ]eCl−
[ ]iK +
[ ]iCl−
=⇒
[ ]
[ ]i
e
K
K
K
F
TR
U +
+
=+ ln.
.
Nernst’s equation – magnitude of the resting membrane potential
equals approximately to the equilibrium point of the pottasium
iones
Equilibrium point for pottasium iones depends on:
R - universal gas constant
T - thermodynamic temperature
F - Faraday’ constant
- concentration of pottasium iones
in extracellulary space
- concentration of pottasium iones
in intracellulary space
[ ]eK +
[ ]iK +

7. Resting membrane potential
[ ] [ ] [ ]
[ ] [ ] [ ]eCliNaiK
iCleNaeK
K
ClPNaPKP
ClPNaPKP
F
TR
U −++
−++
−++
−++
+
++
++
= ln.
.
Goldman’s equation – rather expression of the resting mebrane
potential magnitude because of sodium, pottasium and chloride
iones
P K+ , P Na+ , P Cl- - coefficients of membrane permeability
for pre K+, Na+, Cl-
[K+
], [Na+
], [Cl-
] - concentrations
+

8. •Ion pump, kind of active transport
(energy feed is needed)
•The Na+K+ATPase pump uses energy to
move 3Na+ out and 2K+ into neuron
The Sodium – Potassium Pump (Na+K+ATPase)
Ion pumps
And a result of Na+K+ATPase pump and the leak channels cause a stable
imbalance of Na+ and K+ ions across the membrane. The imbalance in
voltage causes a potential difference across the cell membrane - called the
resting potential. Resting membrane potential is always negative
(-70 mV in humans).

9. • (Na+, K+)-ATPase, in plasma membranes of most animal cells, is
an antiport ion pump. It catalyzes ATP-dependent transport of Na+
out of a cell in exchange for K+ entering the cell.
• (H+, K+)-ATPase, involved in acid secretion in the stomach, is an
antiport pump. It catalyzes ATP-dependent transport of H+ out of the
gastric parietal cell (toward the stomach lumen) in exchange for K+
entering the cell.
• Ca++-ATPases, in endoplasmic reticulum (ER) and plasma
membranes of many cells, catalyze ATP-dependent transport of Ca+
+ away from the cytosol, into the ER lumen or out of the cell. Some
evidence indicates that these pumps
are antiporters, transporting protons
in the opposite direction. Ca++-ATPase
pumps function to keep cytosolic [Ca++]
low, allowing Ca++ to serve as a signal.
Ion pumps

10. Active transport
Active transport is the transport of biochemicals, and other
atomic/molecular substances, across the membranes. Unlike passive
transport, this process requires the expenditure of cellular energy to move
molecules against their concentration gradient.
Primary transport - energy from hydrolysis of ATP is directly coupled to
the movement of a specific substance across a membrane independent of
any other species.
Secondary active transport, the required energy is derived from energy
stored in the form of concentration differences in a second solute.
Typically, the concentration
gradient of the second solute
was created by primary active
transport, and the diffusion
of the second solute across
the membrane drives secondary
active transport of the first solute.

11. Active transport

12. The action potential (AP)
Occures when neurone send information down the axon, reversion of the
membrane potential is caused because of stimulus application.
AP has two main phases:
depolarization - a stimulus cause the
membrane potential to change. This
change is detected by the voltage-gated
(sodium, potassium) ion channels. The
sodium channels open for 0.5ms when
the potential reaches threshold level as
an effect of the voltage change. This
results in sodium ions entering inside
and making the inside of the cell more
positive.
The normal voltage polarity (negative inside) is reversed (becomes
positive inside the cell).

13. Repolarization - at a certain
point, the depolarisation of the
membrane causes the sodium
channels to close. As a result the
potassium channels open for
0.5ms, causing potassium ions to
rush out, making the inside
more negative again
The action potential (AP)
A slight ‘overshoot’ in the movement of potassium ions (called
hyperpolarisation) became marked. The resting membrane potential is
restored by the Na+K+ATPase pump
The original polarity is restored

15. The action potential (AP)
“All or nothing” low – only if the stimulus causes enough sodium ions
to enter inside the cell to change the membrane potential to a certain
threshold level, AP is created. It is necessary to achieve this threshold.
Absolute refractory period
• during AP, the second stimulus will not cause a new AP
• Na+ channels are open or recovering
Relative refractory period
• second AP may be created only if the stimulus has to be great, it is
more difficult to generate it
• occurs when the membrane is hyperpolarised (-80mV), where the K+
channels are open

16. The action potential (AP)
Channel2.swf

17. Propagation of the action potential
3 processes of the AP propagation are possible:
• mechanism of local current – AP is moved along an axon automatically.
The local reversal of the membrane potential is detected by the
surrounding voltage-gated ion channels, which open when the potential
changes enough.
• saltatory propagation – myelin sheath is interruped by nodes of Ranvier
and behave between them as a electrical insulator. AP jump from one node
to another. This increases the speed of propagation (from 1m/s
in unmyelinated neurons up to 100 m/s in myelinated neurons)
• synaptic propagation – see the next chapter

18. propagation of the impulses – comparison
betwen healthy and damaged nerve
Propagation of the action potential
Factrors which may cause affection of the
AP velocity:
• temperature
higher temperature = faster velocity
• axon diameter
larger diameter = faster velocity
• myelin sheath – saltatory propagation
of AP is faster

19. The synapse – active connection between neurons
Electrical - direct connection between neurons
Chemical – there is a space between neurons. Neurons communicate
by neurotransmitters (chemical molecules)
Excitatory - increase probability of impulse generation
Inhibitory - decrease probability of impulse propagation
Synaptic propagation
Propagation of the action potential

20. 1. The action potential activates a
calcium channel and Ca++ diffuses
into the neuron.
2. This Ca++ causes vesicles to fuse
with the cell membrane. Through
exocytosis, neurotransmitters
(chemicals) are released into the
synapse.
3. These neurotransmitters diffuse
across the synapse and bind to
receptors on another neuron. This
causes special Na+ channels to
open and an action potential is
initiated in the next neuron.
Synaptic propagation of AP between two neurons

21. The synapse
Excitatory and inhibitory synapse

22. How many synapses
are in one neuron?
1,000 to 10,000

23. Strength duration curve
Chronaxie - The minimum interval of time necessary to electrically
stimulate a muscle or nerve fiber, using twice the minimum current
needed to elicit a threshold response.
Reobase - The minimal strength of an electrical stimulus that is able to
cause excitation of a tissue.
bireflexarc.swf

24. The action potential (AP)
Single unit activity
Multipotential

25. Electrical activity of the muscle
Human body contains over 400
skeletal muscles, 40-50% of total
body weight
Functions of skeletal muscle
• force production for locomotion
and breathing
• force production for postural
support
• heat production during cold stress
Microstructure:
Sarcolemma - muscle cell membrane
Myofibrils - threadlike strands within muscle fibers
• Actin (thin filament)
Troponin
Tropomyosin
• Myosin (thick filament)

26. Electrical activity of the muscle

27. The light areas are called the I-BANDS and the darker areas the A-
BANDS. Near the center of each I-BAND is a thin dark line called the
Z-LINE (or Z-membrane in the drawing below). The Z-LINE is where
adjacent sarcomeres come together and the thin myofilaments of
adjacent sarcomeres overlap slightly. A sarcomere can be defined as the
area between Z-lines.
Electrical activity of the muscle

28. Electrical activity of the muscle

29. Electrical activity of the muscle
1. The impulse is transferred from a neuron to the SARCOLEMMA of a
muscle cell.
2. The impulse travels along the SARCOLEMMA and T-TUBULES. From
the T-TUBULES, the impulse passes to the SARCOPLASMIC
RETICULUM (SR).
3. The calcium gates in the membrane of the SR open. As a result,
CALCIUM diffuses out of the SR and among the myofilaments.
4. Calcium fills the sites in the TROPONIN molecules. This alters the shape
and position of the TROPONIN which causes movement of the attached
TROPOMYOSIN molecule.
5. Movement of TROPOMYOSIN permits the myosin head to contact
ACTIN.
6. Contact with ACTIN causes the
myosin head to swivel.

30. Electrical activity of the muscle
7. During the swivel, the myosin head is attached to ACTIN.
When the HEAD swivels it pulls the ACTIN (and, therefore, the
entire thin myofilament) forward. Many MYOSIN HEADS are
swivelling simultaneously, or nearly so, and their collective
efforts are enough to pull the entire thin myofilament).
8.At the end of the swivel, ATP fits into the binding site on the
cross-bridge and this breaks the bond between the cross-bridge
(myosin) and actin. The myosin head then swivels back. As it
swivels back, the ATP breaks down to ADP and P and the cross-
bridge again binds to an actin molecule.
9. As a result, the HEAD is once again bound firmly to ACTIN.
Because the HEAD was not attached to actin when it swivelled
back, the HEAD will bind to a different ACTIN molecule (i.e.,
one further back on the thin myofilament). Once the HEAD is
attached to ACTIN, the cross-bridge again swivels, so step 7 is
repeated

31. Electrical activity of the muscle
Types of contractions:
1 - isotonic - tension or force generated by the muscle is greater than the
load and the muscle shortens
2 - isometric - load is greater than the tension or force generated by the
muscle & the muscle does not shorten
Twitch - the response of a skeletal
muscle to a single stimulation:
latent period - no change in length;
time during which impulse is traveling
along sarcolemma to sarcoplasmic
reticulum, calcium is being released,
and so on (in other words, muscle
cannot contract instantaneously!)
contraction period - tension increases
(cross-bridges are swivelling)
relaxation period - muscle relaxes
(tension decreases) and tends to return
to its original length

32. Electrical activity of the heart muscle
electrical activity initiates the heart muscle to contract causing the
opening and closing of the valves to deliver the blood around the body
and back to the heart and lungs.
Myocard – spetial type of
muscle – two muscle cells
are conneted by intercalar
discs. The mechanical
connection enables
transport of the impulses
Plateau phase – result of permeability
for Ca ++ ions increasing, AP in
ventricle (0.3s)

33. Electrical activity of the heart
1. sinoatrial node - an area of nerve cells
known as the pacemaker situated in the
upper wall of the right atrium. Impulese
are initiated there
2. electrical impulse is picked up by a
further electrical node called the
atrioventricular node, which is situated
in the lower part of the right atrium
close to the valves between the upper and
lower chambers of the heart
3. impulses flow down the central wall of
the heart (called the septum), between
the two ventricles and into the left and
right bundle branches via the electrical
conductive tissue to carry the impulse
over each of the ventricles.
1 Sinoatrial node (Pacemaker)
2 Atrioventricular node
3 Atrioventricular Bundle
(Bundle of Hiss)
4 Left & Right Bundle branches
5 Bundle Branches (branches of
Purkyne)

34. Electrical activity of the heart
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35. Elektrická aktivita srdca

36. Electrical activity of the heart
An electrocardiogram (ECG) represents the electrical current moving
through the heart during a heartbeat.
P wave – depolarization
of the atria
QRS complex –
depolarization of the
ventricles
T wave – repolarization
of the ventricles

37. Biological signal - properties
May be defined as a carrier of
informations, which are expressed
by its properties
Basic properties of biological signal:
• wavelength
• amplitude
• frequency

38. Biological signal - properties
Time and frequency domain

39. Biological signal - properties
Ventricle tachycardia (on the left) broken by the defibrilator charge,
normal rhythm on the right side

40. for attention
© 2007 Juliana Knocikova