Escolar Documentos
Profissional Documentos
Cultura Documentos
Sept., 2008
i. Abstract
Resting membrane potential cannot carry any signal unless and until it is
transformed to graded potential and then to action potential. Only action
potential can be propagated to carry the message about a stimulus so that
appropriate response can be elicited in the target cell. A stimulus triggers
transformation of resting membrane potential at special sites of an
excitable tissue (at a receptor or sensor, post-synaptic membrane, endplate surface of skeletal muscle, or pacemaker) to produce graded
potential. This is due to stimulation of chemical-gated or mechanicallygated ion channels that open and cause a change the permeability of the
membrane to certain ions. If the stimulus produces a graded potential
that depolarises enough to reach threshold, this voltage difference will
stimulate voltage-gated ion channels located close to the receptor site.
The membrane will depolarize to form an action potential. This
depolarization will in turn stimulate the next voltage-gated channel along
the axon and another action potential is produced. This process
continues to occur until the action potential reaches the axon terminal,
thus carrying the message about the stimulus to be communicated to the
next neuron or effector cell.
ii. Content
1.
2.
3.
Concept of threshold
4.
5.
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vi
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Content
Page
Abstract
Learning Resources
Background Knowledge
Terms to Know
Objectives
Learning Activities
Membrane potentials as information signal
1.1. The role of the nervous system in
intercellular communication
ACTIVITY 6.1: Significance of intercellular
communication
1.2. From resting membrane potential to
information signal
ACTIVITY 6.2: Membrane potential as
information signal
1.3. Membrane potentials and ion channels
ACTIVITY 6.3. Significance of ion channels
ACTIVITY 6.4: Implication of ionic diffusion
via gated channels
1.4. Locations of the leakage and gated channels
and their implication
ACTIVITY 6.5. Locations of membrane channels
Change in membrane potentials when
stimulated: Graded potential
2.1. From resting potential to graded potential
ACTIVITY 6.6: Equilibrium potential
ACTIVITY 6.7: Demonstration on change in
membrane potential
ACTIVITY 6.8: Demonstration of depolarisation
ACTIVITY 6.9: Graded potential
2.2. Graphical representation of graded potential
ACTIVITY 6.10: Analysing membrane potential
graphically
2.3. Analysis of graded potential
ACTIVITY 6.11: Molecular mechanism of graded
potential
ACTIVITY 6.12: Types of graded potentials
ACTIVITY 6.13: EPSP and IPSP
ACTIVITY 6.14: Graphs of graded potential
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Comments on
mastery
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Concept of threshold
ACTIVITY 6.15: Stimulus-response relationship
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Change in membrane potentials when
stimulated: Action potential
ACTIVITY 6.16: Action potential
ACTIVITY 6.17: Mechanism of action potential
production
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Conduction/propagation/transmission of action
potential
5.1. Mechanism of action potential propagation
ACTIVITY 6.18: Mechanism of action potential
propagation
ACTIVITY 6.19: The domino effect of action
potential propagation
5.2. The significance of refractory periods
ACTIVITY 6.20: Relevance of refractory periods
5.3. Strategies to hasten action potential
propagation
ACTIVITY 6.21. Saltatory conduction of action
potential
vii Summary
viii Conclusion
ix Assessment
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iv.
Learning Resources
Animations:
1. http://www.tvdsb.on.ca/westmin/science/sbioac/homeo/action.htm action potential
2. http://www.accessexcellence.org/RC/VL/GG/action_Potent.html Propagation of
action potentials
v. Background knowledge
To complete this module successfully, you should have the following background:
Knowledge on the general structure and functions of cell membranes (Module 2).
Knowledge on the mechanisms of solute transport across cell membrane (Module 3).
Knowledge on the basic mechanism of signal transduction (Module 4).
Understanding of the definition of chemical and electrical gradients (Module 5).
Knowledge on membrane potentials of excitable tissues at rest (Module 5).
hydrophobic
hyperpolarized
inhibitory post-synaptic potential (IPSP)
ion binding sites
membrane permeability
membrane potentials
milliseconds (msec).
Na + /K + -ATPase
net charge
net movement
passive channels
phospholipid bilayer
receptor site
resting membrane potential
semi-permeable
solute
solvent
threshold
voltage activated gates
voltmeter
Please add other terms that you feel are relevant to your understanding of this module.
Please set up more specific objectives after youve thoroughly studied the material in this
module to help yourself in your revision later on. Make notes that meet the requirement of
the new objectives.
Receptor
Control
centre
Effector
The key molecules that are involved in producing information signal on a cell membrane
are the proteins such as receptor and channel proteins. Before we look at what happens to
the membrane potential when stimulated, lets review the relationship between ion
channels and membrane potentials.
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Passive
(leakage)
Chemicalgated
Active
(gated)
Voltagegated
Mechanicallygated
What is the implication of the number of leakage K and Na channels in plasma membrane to
the resting potential? You have calculated the EK+ and ENa+ using the Nernsts equation, and
the EM using the Goldmans equation. Why is the resting membrane potential closer to the
+
+
equilibrium potential of K compared to that of Na ?
Predict what happens to a cell that has only leakage channels (no gated channels) when it is
stimulated by an appropriate stimulus. Which type of cell has no gated channels? Which type
of cell has gated channels? What is the advantage of having gated channels? Why dont all
cells have gated channels? What kind of gated channels exist in receptor cells that directly
respond to internal and external environmental stimuli?
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Ions move along chemical and electrical gradients (electrochemical gradients) through
the channels, carrying the +ve or ve charges. This will cause a change in membrane
potential. Activity 6.4 helps you to clarify this phenomenon.
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1.4. Locations of the leakage and gated channels and their implication
Leakage channels are found almost everywhere on a cell membrane. However, the
number of individual channels on a cell membrane may be different (refer to Activity 6.8).
Chemical/mechanical-gated channels are located on:
nerve endings or receptor (sensor) sites
post-synaptic membrane
pacemaker cells
muscle (neuromuscular junction)
Voltage gated channels are located at axon hillock and along the axon distal to receptor
region (Fig. 6.5)
ACTIVITY 6.5: Locations of membrane channels
List down the locations of leakage channels, chemical-gated and mechanical gated channels in
cell membrane. Hypothesise the significance of the locations of the leakage and gated
channels.
Based on Fig. 6.5 suggest the function of:
Input zone, Trigger zone, Conducting zone, Output zone
What ion channels are present at the above zones? What are the implications?
Figure 6.5. The input zone, trigger zone, conducting zone, and output zone on a neuron.
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In Activity 6.7 you will demonstrate the change in membrane potential by working on the
template model (use the model in Appendix A in Module 5).
ACTIVITY 6.7: Demonstration on change in membrane potential
+
Set up your membrane template (Appendix A in Module 5) with a K channel in one gap, and a
+
Na channel in the other (Appendix B in Module 5). To each of these channels lay a gate
across the opening on the outside of the membrane. The small notch in the gate should face
up.
+
Add the following ions to the ISF: 10 Na , 1 K , and 3 Cl . Add the following ions to the
+
+
cytoplasm: 1 Na , 10 K , and 1 Cl . Please do not disregard the 20 negative charges inside
the model cell due to protein. Note that these do not represent physiological proportions, but
will be useful for helping you do the simulations.
Determine by the counting technique you learned in Module 5 what the membrane potential is
for this model cell.
Observe the channels that you set up on your template. What types of channels are these?
Specify both the ion and the means of opening/closing.
One type of gated channel that is vital for communication between cells in the body is
controlled chemically. What does this mean?
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These chemical-gated (or ligand-gated) channels are found, for example, on the skeletal
muscle cells innervated by the motor neurons. So when you decide to flex your arm at the
elbow (Fig. 6.1), the signal is sent out to the skeletal muscle cells of the biceps brachii
muscle by means of motor neurons that signal the muscle to contract. In this example, the
motor neurons release a chemical signal (a neurotransmitter called acetylcholine) that
attaches to the channel protein at a special receptor site. The binding of the chemical
signal to the receptor causes the gate to open briefly, causing membrane depolarization.
Activity 6.8 helps you to understand the above concept better.
ACTIVITY 6.8: Demonstration of depolarisation
Continue your work from Activity 6.7. Choose the square signal molecule for your model,
+
attach it to the receptor site on the gate of the Na channel, and rotate the channel to an open
position. Demonstrate what happens to the sodium ions.
The attachment between the signal molecule and the receptor site is weak. Soon it
detaches and the gate closes. Demonstrate it. The signal molecule is then split apart by an
enzyme (not shown here) in the cell membrane. You can simulate this by simply removing the
square signal molecule.
Based upon what you have learnt so far, predict what will happen to membrane potential when
+
Na gate is opened.
Test your prediction by running the following simulation: Attach the signal molecule to the
+
channel, open the gate, move 3 Na into the cell, and close the gate. Determine the new
+
membrane potential and record it. What forces tend to move Na into the cell?
If you did it correctly, there is a change in membrane potential called depolarization of the
membrane. What does depolarization mean? Draw a graph showing resting membrane
+
potential and how this potential changes when Na channel is open.
Confirm that the potential difference across the membrane was reduced (went closer to zero).
Thus depolarization takes the membrane from its resting potential closer to zero.
Try to produce a computer animation of the above process.
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In Activity 6.8, the influx of Na+ ions creates a new gradient inside the cell (i.e. charge
difference underneath the membrane between the site of Na+ entry and the adjacent sites
i.e. the dark band in Fig. 6.6a). To understand this, consider the concentration of sodium
ions in the cytoplasm directly beneath the channel compared to the concentration in the
adjacent area. What is the gradient? Refer to Fig 6.6a. What do you expect will happen to
the extra Na+ ions that just came in?
The resulting diffusion of ions creates a tiny current in the cell. It also will restore the
local membrane potential back toward the resting value (Fig 6.6b). Fig. 6.7 shows what
happens in a graphical format.
Figure 6.6 a. Stimulation of the membrane causes deplarisation; b. The positive charges spread to
the neighbouring sites
Figure 6.7. Graphical representation of the spread of charges from the site of depolarization.
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Now you know what happens when the cell is stimulated by a ligand that sits on its
receptor, causing the gated ion channel to open. If the stimulus causes Na+ channel to
open, Na+ will rush in, depolarizing the membrane from its resting state. The Na+ ions
will be attracted to the negative charges of the neighbouring sites and soon the membrane
potential falls back to the resting state. This type of transient depolarization is called
graded potential.
Activity 6.9 helps you to explore more about graded potentials.
ACTIVITY 6.9: Graded potential
What is graded potential? Can graded potential be used to carry information? Predict the
function of graded potential.
Description
Potential = potential
difference
Membrane potential
Equilibrium potential
Resting potential
Graded potential
Action potential
Synaptic potential
Receptor potential
Pacemaker potential
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0
-20
-40
-60
-80
e
-100
f
1
6 7
9 10 11 12 13 14 15
Time (msec)
Figure 6.8. Change in membrane potential when a cell is stimulated
The graphs in Fig 6.8 shows a recording of what happens to the membrane potential when
2 separate cells are stimulated (at the arrow, time=1 msec.)
Activity 6.10 helps you to analyse the graph clearly.
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Activity
6.12
helps
you to identify
the different
types
of graded potentials that occur in
ACTIVITY
6.11:
Molecular
mechanism
of graded
potential
your body.
For each of the characteristics mentioned above, please explain the molecular mechanism
involved.
Pacemaker potential
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The graded potential events represented in Fig 6.10 are frequent occurrences in neuron and
muscle cells. For example, the brief depolarization of the membrane of a post-synaptic
neuron in response to a chemical signal (neurotransmitter) is called an excitatory postsynaptic potential (EPSP). It is so named because it increases the likelihood that the cell
will produce an action potential, another type of communication signal (Section 4).
The hyperpolarization in Fig 6.10 is called an inhibitory post-synaptic potential (IPSP).
These signals have the opposite action of EPSPs. They decrease the likelihood that the cell
will produce an action potential. Some neurotransmitters cause depolarization while
others cause hyperpolarisation.
ACTIVITY 6.13: EPSP and IPSP
In Fig 6.11 draw a graph from the data in the table provided. The recordings in the table are
from two different cells. Plot the points and connect them to make the curve.
When you have completed the graphing, label the segments of each curve by referring to
Fig 6.8. (A new segment begins with a change in direction of the curve). You may need to
use more letters on the top curve than the bottom.
Next, interpret in words what is happening in each segment of the curve. Suggest what is
happening in the membrane to bring about the changes from one segment to the next.
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0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
5.0
Membrane
potential (mV)
Cell 1
Cell 2
-60
-75
-60
-75
-60
-75
-50
-75
+20
-84
-50
-88
-60
-84
-65
-75
-63
-75
-60
-75
-60
-75
20
0
Membrane potential (mV)
Time
(msec)
-20
-40
-60
-80
-100
1
Time (msec)
Figure 6.11. Membrane potential recordings for two cells
What is the relevance of graded potential? If it cant carry signals over long distance,
what is it for? Graded potential is actually important in initiating action potentials, the
long distance signals. How is this possible?
Before answering the above questions, lets first look at the concept of threshold.
3. Concept of threshold
What is threshold stimulus? It is a stimulus which is strong enough to cause formation
of action potential.
What is threshold potential? It is a membrane potential (voltage) which is strong enough
to stimulate voltage-gated channels to open. It is normally ~15mV above resting
potential.
To understand the concept of threshold stimulus and threshold potential, lets carry out
the Activity 6.15:
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Membrane
potential (mV)
Threshold
potential
Stimulus
strength
Resting
membrane
potential
Threshold
stimulus
Time
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Review:
Action potentials occur in certain parts of the cell membrane where there are
voltage-gated channels.
Stimulus for generation of action potential is graded potential. It involves voltagegated channels at axon hillocks or proximal to receptor regions
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i.
ii.
Activation gate
Inactivation gate
Please use Fig. 6.14 to figure out the involvement of the gates in the formation of an
action potential.
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Fig. 6.15. Ionic mechanism associated with the phases of action potential
The depolarization phase of the action potential generated when the membrane reaches
threshold actually has a positive-feedback relationship (Fig. 6.16). The threshold
potential causes opening of the voltage-gated Na+ channels which will increase the
permeability of the membrane to Na+. This will increase the flow of Na+ into the cell and
will enhance depolarization. The positive feedback continues until all the voltage-gated
Na+ channels are open. When the voltage-gated Na+ channels close, the membrane
repolarises (Fig. 6.16).
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You should be comfortable with the relationship between graded potential and action
potential now. Table 6.2 describes the comparison between graded potential and action
potential.
Table 6.2.
Graded potential
Action potential
Conducted decrementally
Duration constant
Depolarisation with overshoot
Initiated by graded potential
Can be summed
Has no threshold
You know that action potential is of no use in terms of signal carrying capacity unless it
can be propagated. Let us now explore how action potential is propagated and form what
is known as impulses.
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Mechanism of action
potential propagation
Fig. 6.17. Formation of consecutive action
potential.
Note the timing
of action potential
Review
the positions
of chemical-gated
(or
+
formation in the three
panels.
mechanically-gated)
and
voltage-gated Na
channels on the membrane of neurons.
Follow the explanation below while referring
to Fig. 6.17.
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Activity 6.19 helps you to feel the process of action potential propagation and to relate it
to the strength of the stimulus.
ACTIVITY 6.19: The domino effect of action potential propagation
Arrange about 20 dominos on the floor.
First give a little push to the first domino; use a force that is not sufficient to cause the
domino to fall. What do you notice? Relate it to the subthreshold stimulus. The
stimulus you gave was not strong enough to cause the first domino to fall onto the
second domino, just like a subthrehold stimulus is not strong enough to depolarize the
neuron to open the voltage-gated channel.
Give a stronger push onto the first domino until it is just sufficient to fall onto the second
domino. What do you notice?
Once initiated, the action potential is a self propagating process that continues along the
axon at a constant velocity (like domino effect).
Relate this to the events that take place in a neuron when a threshold stimulus is
applied.
Hypothesise what would happen if you push the first domino harder. Verify this by
timing the fall of the 20 dominos. Compare this to the threshold and suprathreshold
effects of stimuli.
Please use the analogy of the connection between one domino and the next domino to
the connection between one action potential to the next action potential in a neuron.
Please explain based on the molecular level.
Relative refractory period: a period when action potential can only be formed when
the stimulus is stronger than the normal threshold.
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Activity 6.17 helps you to understand more about the relevance of refractory periods.
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Axon diameter also affects the rate of action potential conduction. Larger diameter axons
propagate impulses faster than smaller ones. Therefore, information that requires vey fast
response (for example sensory inputs and motor outputs to muscles and joints) is
transmitted by thicker fibres.
Effect of axon diameter on speed of conduction:
Group A fibres: largest diameter ~5-20mm; all myelinated; somatic sensory (touch,
pressure) and motor fibres to skin, muscle and joints; speed of conduction: 12-
130m/sec
Group B fibres: diameter 2-3mm; lightly myelinated; conduct sensory impulses to
CNS, and all ANS axons to autonomic ganglia; speed: up to 15 m/sec
Group C fibres: diameter 0.5-1.5mm; all unmyelinated; conduct sensory impulses for
pain, touch, pressure, heat and cold from the skin, and pain impulses from the viscera.
Include autonomic fibres from autonomic ganglia to heart, smooth muscle and glands.
Speed: 0.5-2m/sec)
Chemical factors can also affect impulse conduction. These are substances which alter
membrane permeability to ions, thus influence the rate of impulse conduction. For
example:
Ca2+ are required to close Na+ channels in axon membranes during an action potential.
Lack of Ca2+ Na+ channels remain open Na+ diffuse in again and again
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vii. Summary
The resting membrane potential itself cannot propagate impulses, thus it cannot transmit
information signals. However, it is a basis for production of graded potentials when the
membrane is stimulated. This is due to the membrane characteristics of excitable cells i.e.
by having gated ion channels that are responsive to chemicals, change in voltage, or
mechanical stimulation. The action potentials produced are propagated along the axon due
to the presence of voltage-gated ion channels on the axon membrane. This is how
information signal is transmitted from the receptor (sensor) to the central nervous system
(CNS) for processing, and from the CNS to the effector for appropriate response to the
stimulus.
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viii. Conclusions
Please make sure that you achieve all the objectives set up at the beginning of this module:
Objectives
1. Explain the role of the nervous system in
intercellular communication.
2. Predict the sequence of events that take place
on a cell membrane when a stimulus reaches
a receptor.
3. Describe the significance of different ion
channels of the membrane of a neuron in
terms of their effects on membrane potential.
4. Define graded potential, describe how it is
established, and describe its characteristics.
5. List down the types of graded potential and
state the significance of each.
6. Compare and contrast between EPSP and
IPSP.
7. Define threshold stimulus and threshold
potential
8. Plot the membrane potential response to
subthreshold, threshold, and suprathreshold
stimuli and explain the molecular basis of the
response.
9. Explain the meaning of action potential.
10. Describe the mechanism of action potential
production.
11. Compare and contrast between action
potential and graded potential.
12. Describe the mechanism of action potential
propagation.
13. Describe the molecular basis of absolute and
relative refractory periods and state the
significance.
14. Describe the strategies that can hasten action
potential propagation.
Comments
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