Another feature on the interface is labeled “Preset Simulations”, and here you can load selected demonstrations. These presets are a great way for a beginning user to see the simulator in action. A review of the basic concepts of action potentials is recommended to get the most benefit. Recommended references are available at the end of this document. However, you can still get a sense of what can be done with the simulator if you’re new to these concepts. There are four examples that will be discussed. The names for these presets are large amplitude stimulus, small amplitude stimulus, refractory period, and repetitive spiking.
The first example is called Large Amplitude Stimulus and demonstrates a basic action potential. The two key settings for this demonstration are a pulse duration of 0.15 ms and an amplitude of 800 µA. You can load this preset using the button in the preset area labeled “Large Stimulus”. When you click on this button, it will load the parameters and automatically run the simulation. If everything worked as planned, you should see the classic action potential shape in black. Note that we used a start time of 0.1 ms for the stimulus. We did this in order to clearly see the resting behavior of the membrane before the pulse. This may be desirable, but it is not necessary for the simulation. Using a start time of 0 ms should make no difference.
The second example is called Small Amplitude Stimulus, and it demonstrates an action potential using a different combination of pulse duration and amplitude. You can load this demonstration using the button labeled “Small Stimulus” in the preset section. In this example, we use one pulse with a duration of 1.0 ms, which is longer than in the first example, and a lesser amplitude of 320 µA. In this case, an entire millisecond is necessary in the stimulus before the membrane voltage exceeds 0 mV. Because the behavior of interest requires more observation time, the simulation length has been increased to 2.0 ms.
The third example is called Refractory Period, and it demonstrates a special behavior of excitable membranes. Here, we have two pulses, but only the first pulse will generate an action potential. Like the first example, it uses an initial pulse with a duration of 0.15 ms and an amplitude of 800 µA. To load the demonstration, click on “Refractory Period”. Notice that an initial action potential is generated, just as was seen in the first example. In this new example, however, an additional pulse is given with a start time of 1.6 ms and the same duration and amplitude as the first pulse. The simulation length is 2.0 ms which is long enough to see that the second pulse does not generate an action potential, but does generate a small depolarization. The refractory period is a time period following an action potential in which the internal mechanisms of the membrane have not been reset to their original state. As a result, these mechanisms are not yet capable of producing another action potential. As an exercise, you might play with the settings to see how early the second pulse can be in order to yield a second action potential. To try this, you would increase the start time for the second pulse. Note that you will also need to increase the run length in order to actually see the result.
The fourth example is called Repetitive Spiking, and it demonstrates the effect of using an extended stimulus as is sometimes done in electrophysiological experiments. It uses one pulse with a much longer duration of 10.0 ms, and a moderate amplitude of 500 µA. In order to see the effect, the simulation length is 10.0 ms and a special parameter change is made to the model that will be discussed below. After you load the “Repetitive Spiking” preset, you should notice three action potentials. Loading the preset should make this parameter change automatically. Note that the simulation length is such that the pulse will still be active at the end. This does not cause a problem because the pulse is not required to be complete during the simulation.
The result of these settings is an initial action potential, or “spike”, that is followed by two smaller spikes of lesser amplitude. This demonstrates how more detailed investigations may be performed using the model parameters. The behavior observed here does not occur with the model using the default parameters from the previous examples. The particular parameter that is different is a potassium conductance that is identified in the original model as “gKs” (Schwarz et al. 1995). Advanced users can see the change by using the “Hide/Show Parameters” button and checking that the parameter labeled gKs is set to zero. To restore the default parameter value of 30 nS, the user can load any one of the other presets described earlier. Alternatively, the value 30 can be entered into the textbox for the gKs parameter.