The Ionic Basis of The Membrane Potential (V_m)

Notes & Tips

1. Depending on your monitor's settings, you may find that the entire display is not visible on your monitor's screen. For instructions on how to increase the viewing area on your monitor's screen, click here.

2. Depending on the settings you're using, the display may become cluttered with lines, and the numerical values for V_m may become difficult or impossible to read after only two runs. Should this occur, simply click the "Clear" button to clear the display without changing the parameter values you've specified.

3. Before conducting the experiments outlined below, you may want to refresh your memory about the Ionic Basis of the Membrane Potential.

4. It will enhance your learning experience if you predict the result of the concentration and/or conductance changes you've made before you click the "Go" button and run the simulation. By comparing the actual results with your prediction, you'll be more certain of your degree of understanding of the V_m phenomenon.

5. You should print out the Experimental Protocol section along with the included tables, and fill in the tables as you progress.

6. If the simulation won’t run properly, here are some suggested fixes:

a. If you’re using an IBM-compatible machine, click here.

b. If you’re using a MacIntosh machine, click here.

Experimental Protocols

Start the simulation by clicking on the “Run The Simulation” link. When the simulation has loaded, spend a little time familiarizing yourself with the appearance of the display, and its features. Once you have done that, click the "Go" button to do a run using the default settings for ion concentrations and conductances. What is the value of V_m?

I. Effects of [Na⁺]

If you've changed any of the default values or have made more than one run with the default settings, Clear and Reset the display. Now, conduct runs to complete the following tables, using the given values for [Na⁺]_ext and [Na⁺]_int (leave [K⁺]_ext and [K⁺]_int set at their default values). Be sure to make a prediction about the relative value of the resulting equilibrium V_m before you do the run. If your prediction is confirmed by the results of the subsequent run, congratulations! If it isn't, try to figure out where you went wrong. To help you get started, I've done the first experiment for you.

[Na^+]ext	[Na^+]int	Predicted Effect On Vm	Result	Prediction Confirmed?	Notes
120	10	n/a	-76.5 mV	n/a
80	10	Hyperpolarized è > -76.54 mV	- 81.6 mV	Yes	Woo-hoo!!
40	10
0	10
180	10
240	10

Now, Clear and Reset the display, and do runs using the indicated settings for [Na⁺]_int.

[Na^+]ext	[Na^+]int	Predicted Effect On Vm	Result	Prediction Confirmed?	Notes
120	10	n/a	-76.5 mV	n/a
120	5
120	0
120	30
120	50

II. Effects of [K⁺]

Clear and Reset the display. Now, conduct runs to complete the following tables, using the given values for [K⁺]_ext and [K⁺]_int (leave [Na⁺]_ext and [Na⁺]_int set at their default values). Once again, be sure to make a prediction about the relative value of the resulting equilibrium V_m before you do the run. If your prediction isn't confirmed, try to figure out where you went wrong.

[K^+]ext	[K^+]int	Predicted Effect On Vm	Result	Prediction Confirmed?	Notes
3	140	n/a	-76.5 mV	n/a
2	140
1	140
0	140
5	140
10	140

Now, Clear and Reset the display, and do runs using the indicated settings for [K⁺]_int.

[K^+]ext	[K^+]int	Predicted Effect On Vm	Result	Prediction Confirmed?	Notes
3	140	n/a	-76.54 mV	n/a
3	70
3	0
3	180
3	255

III. Effects of g_Na+

If you've changed any of the default values, Clear and Reset the display. Now, conduct runs to complete the following table, using the given values for g_Na+. Be sure to make a prediction about the relative value of the resulting equilibrium V_m before you do the run. If your prediction is confirmed, congratulations! If it isn't, try to figure out where you went wrong. Note: if it's necessary to read the numerical values for V_m, you may Clear the display between runs.

gNa+	Predicted Effect On Vm	Result	Prediction Confirmed?	Notes
1	n/a	-76.5 mV	n/a
2
3
10
20
700

IV. Effects of g_K+

Clear and Reset the display. Now, conduct runs to complete the following table, using the given values for g_K+. Once again, be sure to make a prediction about the relative value of the resulting equilibrium V_m before you do the run. If your prediction isn't confirmed, try to figure out where you went wrong..

gK+	Predicted Effect On Vm	Result	Prediction Confirmed?	Notes
33	n/a	-76.5 mV	n/a
23
13
43
53
255

Questions and Exercises

1. Try setting g_Na+ = 33 and g_K+ = 1. Was the resulting V_m positive or negative? Explain your result.

2. Based on your results, can you provide an explanation for the effects of changing [Na⁺]_ext on V_m? How about for the effects of changing [Na⁺]_int?

3. Based on your results, can you provide an explanation for the effects of changing [K⁺]_ext on V_m? How about for the effects of changing [K⁺]_int?

4. Once you've completed Questions #1 & #2, provide an explanation for the effects on V_m of changing g_Na+ and g_K+.

5. A rare but troublesome affliction in humans is a condition known as Familial Periodic Paralysis (FPP). As its name indicates, it’s a genetic affliction, and victims suffer recurring bouts of fatigue, weakness, even paralysis. Muscle function is pretty much normal between bouts, although recent research suggests that subtle but progressive degenerative changes in muscle structure may be occurring. A number of types of FPP are known, but the most common form is inherited as an autosomal dominant trait, meaning that only one parent must transmit the gene to produce an affected offspring. Most types are more common in males than in females.

Although there is some controversy in the contemporary research literature about the mechanisms underlying the signs and symptoms of FPP, the most consistent laboratory finding is a reduced [K⁺] in the blood and extracellular fluids. This is usually the result of a shift of K⁺ into the intracellular fluid compartment, but occasionally appears to result from excess renal secretion of K⁺ into the urine. Whatever the mechanism for the hypokalemia (abnormally low [K⁺] in the body fluids), a decrease of as little as 5% in the extracellular [K⁺] can be associated with muscle weakness.

For this exercise, you are to use the [K⁺]_ext and [K⁺]_int controls to simulate the changes in potassium balance (i.e., ¯[K⁺]_ext and [K⁺]_int) and observe the effect on V_m. Then, keeping in mind that an excitable cell must be depolarized all the way to its threshold V_m (usually 10 – 30 mV less than resting V_m) before it can generate and propagate an action potential, you are to use your results to suggest an explanation for the paralysis that is symptomatic of FPP. Does it make sense that an acute episode of FPP can be treated by administration of intravenous potassium?

Advanced Exercises

If you want to explore some more advanced topics in neurophysiology, go to my Physiology Simulations web page and click on the Neurophysiology Simulations link. (There are links to other simulations on this same web page. Feel free to work with as many of the other simulations as you wish.)