Transcript No Slide Title

Simulation of the Action Potential
• In the first lab exercise, you will observe how the
action potential depends on ENa, Ek, and temperature.
• The second lab exercise simulates an action potential
(AP) traveling in an axon which is abnormal due to the
disease multiple sclerosis. This axon has lost its
myelin wrapping over its left half.
bare axon
myelinated axon
First simulation: the stationary action potential
• Click ”Tutorials" on the home page. Look
in the Basic Patch column (on the left) and
click the “Na Action Potential” tutorial.
• The text of this tutorial will be displayed
on the right. Scroll down to this button
and click it.
These two control panels will come up (a third is
beneath them--ignore it). Don't move these panels-more are coming!
Panel and Graph Manager
RunControl
Click "Stimulus Control“ to insert an electrode in the
axon.
This menu will come up.
This blue ball shows that
you have put an electrode in
the axon to inject some
positive current and trigger
the AP.
Now you can ignore this menu.
Click “Voltage vs Time Plot".
This mV vs time graph will
come up. You can resize it.
Click "Reset & Run" in the RunControl panel to
inject a pulse of current and trigger the AP.
Note on the graph that
ENa is represented by
the blue line and Ek by
the brown line.
Click on “Patch Parameters" in the P&G Manager
panel to bring up the menu for doing experiments.
The parameters menu
allows you to change
the ion concentrations
and observe the effect
on the AP.
Change the concentration of Na and K in the blood
(extracellular) using this menu.
How to change a default value:
• Click the up or down arrows
or
• Enter a new value in the white space
(**make sure your cursor is positioned in
the white space).
• Click this box. A red mark will appear indicating
the parameter is changed. You can go back to
the default by clicking it off.
Now change [Na]out (see Q sheet) and rerun the
simulation.
Answer
question 1
Note this readout
of ENa and EK.
Go back to the original Na concentrations.
Now change [K]out and rerun the simulation.
Answer
question 2
Change the temperature in the RunControl menu.
Try 2, 10, and 20 degrees. What happens to the
duration of the AP?
Answer Q. 3.
When you are finished with the “stationary” AP
simulation, click Quit in the Panel and Graph
manager. (Don’t click the upper right corner X.)
Next you will observe a
propagated AP in the
“Partial Demyelination”
tutorial.
Second simulation: an axon affected by
Multiple Sclerosis
• Go to the Axons pull-down menu and
select Partial Demyelination. The text of
this tutorial will be displayed.
• Scroll down as you did before to this
button and click it.
These two panels will come up again, now
specialized for the Partial Demyelination simulation.
Panel and Graph Manager
RunControl
Get ready to observe the AP traveling
from the bare axon, where it travels
slowly,
into the myelinated region, where it
travels rapidly.
Click on Voltage vs. Space in the P&G Manager.
This graph will come up.
Note that mV will be plotted
versus µm (space, not time).
The x axis is the axon.
resting potential = -65mV
Now get ready to "insert" the stimulating
electrode into the axon so that you can
inject current to trigger an AP.
current
Click "Stimulus 'Trode in Bare Axon".
This menu will come up.
This line represents the
axon
This blue ball shows
that the axon will be
stimulated at its left
end.
Click "Reset & Run" in the RunControl panel to
inject a pulse of current and trigger the AP.
The AP should travel
along the axon from
left to right on the
graph. To slow it
down, use slider in
panel, or pause it:
Pausing the AP: Press "Reset" then "Continue for."
This will cause the AP to travel for the time indicated,
pause, and travel again when you click. You can set
the time interval yourself in the white space.
Important! Controlling the rate of the AP
Click “reset”
Set this time
interval to 0.1
Now when you click
“Continue for”, the AP
will advance in 0.1 ms
intervals each time you
click.
Stop the AP as instructed on your
Work Sheet and answer Questions
4 through 9.
• Now get ready to take the electrode out
of the left end of the axon and "insert" it
into the right end.
• Follow the next instructions--**Don’t just
move the blue ball !!!!
Put your cursor right on the word "close" and click it
to close the Stimulus Control panel. (The upper right
box doesn't close these panels).
Closing the panel
removes the
electrode.
Get ready to observe the AP traveling the
other direction:
You will now put the electrode in the righthand end in order to start the AP in the
myelinated portion.
Return to the P&G Manager.
Click on "Stimulus
Trode in Node [4]".
This will insert a
stimulating electrode in
the right-hand end.
A new Stimulus Control panel will come up. The blue
ball (the electrode) is now at the right-hand end.
current
Nodes:
0 1 2 3 4
Click "Reset & Run" in the RunControl panel to
trigger the AP.
What
happens?
Answer
Question 10.
Next: How can you make the AP
propagate into the demyelinated portion
of the axon?
Experiment with changing the temperature.
Multiple sclerosis patients find that
temperature has a strong effect on their
condition.
But do they feel better when they are cooler
or warmer?
Change the temperature in the RunControl menu
and rerun the simulation.
Answer Questions 11 - 13.
Before you go on to the next section, make
sure the temperature is restored to its original
value by unchecking its box.
Experiment with drugs that
affect ion channels.
Design two drugs with separate actions
on the channels in the membrane.
Click on "Bare Axon Parameters" in the P&G
Manager panel.
The parameters menu
that will appear allows
you to change the
properties of the bare
axon.
On the Bare Axon Parameters menu, change a
value for the "density" of the Na and K channels.
If you " block"
channels with a
drug, they are not
available to open,
and thus are "not
there." Thus to
apply this drug you
decrease the
channel density.
Alternatively a drug
might increase
channel density.
Answer Questions 14-16.