Action Potential Generation By the Squid Giant Axon

Introduction

This simulation extends your study of the ionic basis of membrane potentials to the membrane electrical phenomenon known as an action potential. It is based on data from the classic early studies of action potential generation in the squid giant axon by Hodgkin, Huxley, Katz, and others. In addition to providing you with a good understanding of the action potentials generated by neurons, this simulation also provides you with a strong foundation for working with other action potential-related simulations such as the Compound Action Potential and Recruitment of Motor Units simulations.

In a previous exercise in this series, you studied the ionic basis of membrane potentials, using the effects of changing ion concentrations and membrane conductances on membrane potential (V_m) as an investigative tool. You will be using the same basic approach in the present simulation. In this case, however, you will not be specifying membrane conductance values, since it is changes in conductance that underlie the action potential itself.

In addition to getting some practical experience with the basics concepts underlying the ionic basis of the action potential, you will be gathering data that you can employ in tests of a couple of extremely important hypotheses related to action potentials. Thus, along with Membrane Potential and the Voltage Clamp simulations, this simulation will provide you with a good introduction to physiological hypothesis testing.

What Does The Action Potential Simulation Allow You To Do?

This simulation allows you to change [Na⁺] and [K⁺] inside the axon as well as in the surrounding medium, and observe the effects on action potentials being generated by the neuron.

What Does The Action Potential Simulation’s Display Look Like?

Depending on the browser you’re using and the size of your computer’s monitor, when you click on the “Run The Simulation” link, you will see a display that looks similar to this:

The display is dominated by a blank set of x-y axes on which will be plotted graphs of V_m (in mV) versus time (in ms). Four slider/text field combinations are provided that allow you to specify independent values for the external and internal concentrations of Na⁺ and K⁺.

This display can present considerably more information than the display for the Membrane Potential simulation. When you initiate a simulation run, the axon membrane is depolarized to threshold at t = 0 ms (stimulating pulse not shown), and the resulting action potential is displayed out to t = 6 ms as a thick line. However, in addition to the action potential itself, you have the option of displaying labeled graphs of the equilibrium potentials for Na⁺ (e_Na+; labeled E(Na⁺) in the display), K⁺ (e_K+; labeled E(K⁺)), and Cl^- (e_Cl-; labeled E(Cl^-)). As you learned when you ran the Membrane Potential simulation, the values for e_Na+ and e_K+ will change when you change [Na⁺] and/or [K⁺], and the display will be updated to reflect any changes you make in [Na⁺] and/or [K⁺].

Although the default settings will cause e_Na+, e_K+, and e_Cl- to be displayed you have the option of choosing which, if any, will actually be displayed. You do this by means of the three “Display” checkboxes located in the right side of the display. Equilibrium potentials selected for display will appear as thin black lines extending from the y-axis almost all the way to the right hand edge of the display.

In addition to the action potential and equilibrium potential graphs, numerical values for several important quantities are also displayed:

1. The value of V_m at the 'tip' of the action potential ‘spike’ – color-coded values are displayed immediately above the tip of the spike;

2. Maximum V_m during the afterpotential – color-coded values are displayed slightly below the point of maximum hyperpolarization achieved during the afterpotential phase.

3. E(Na⁺), E(K⁺), and E(Cl^-) – if the corresponding checkbox is selected, these values are displayed to the right of their respective graphs.

The color of the displayed numerical values for V_m, e_Na+, and e_K+ change to match the color of the line used to graph the action potential, but the value of e_Cl- ( = -65 mV and invariant in this simulation) is always displayed in black.

In addition to the above mentioned controls, the usual control buttons are provided. Note that clicking the “Reset” button will cause the simulation to run, producing an action potential based on the default settings for [Na⁺] and [K⁺]. The checkboxes, however, are not affected; your selections of which, if any, equilibrium potentials to display will be unchanged by clicking the Reset button. If you wish to change your selections, you will have to do so manually.

Each time you click the Go button to do a run, a color-coded Legend entry will be added at the top of the display. This will make it easier for you to keep track of what experiments you’ve conducted and to keep your results organized on the accompanying data sheet.