Cellular Neurophysiology

Properties of Action Potentials

Luigi Galvani first described experiments in 1791 suggesting that animal cells communicated electrically.¹ This idea that there was a link between electricity and the older concept of a vital life force became a popular sensation, inspiring Mary Shelly’s gothic novel Frankenstein, in which the monster is animated, given life, by electricity. Unfortunately, progress after Galvani was slow. It proved difficult conceptually for many investigators at the time to distinguish Galvani’s ‘animal electricity’, which travelled along animal nerve fibers, from the movement of current through inanimate conductors like a copper wire, a phenomenon that was also much easier to study experimentally. This difficulty in recognizing the unique nature of the ‘active’ propagation of electrical excitation along nerve fibers initially resulted in doubts about the role of ‘animal electricity’ in normal physiology.

Although there was some important advances in applying physical principles to the problem,² the details of electrical conduction in nerves remained largely unresolved until Alan Hodgkin and Andrew Huxley provided a complete description of action potential propagation along axons in 1952.³ Their studies took advantage of a unique biological preparation, the squid giant axon, which was relatively easy to study because of its unusually large size, as well as the development of intracellular recording and advances in electronic instrumentation.

In this section some of the basic properties of action potentials first observed in the squid giant axon are illustrated.

Overshoot

At the peak of the action potential, the membrane potential becomes positive (Figure 1). The height of the peak of the action potential above zero is known as the overshoot. When this phenomenon was first observed it suggested that a transient increase in a conductance selective for sodium ions was involved in generating the action potential. Sodium ions have a Nernst potential positive to zero (\(E_{\mathit{Na}}\) = 50 mV for the model cell), which could create the driving force necessary to move the voltage to such positive potentials.

Figure 1 Electrically excitable model cell. Press the ‘–’ and ‘+’ buttons to change the equilibrium potential for sodium ions. The membrane potential (top panel), and the injected current stimulus (bottom panel) are shown.

Further evidence for this idea came from changing \(E_{\mathit{Na}}\) by changing the concentration of external sodium ions.⁴ In the model cell reduce \(E_{\mathit{Na}}\) and observe how the peak of the action potential declines. The peak of the action potential is dependent on \(E_{\mathit{Na}}\). Note that the peak never exceeds \(E_{\mathit{Na}}\) and is always somewhat less due to the presence of other types of ion selective channels, particularly potassium selective channels that also influence the membrane potential.

Threshold Depolarizing Current

The response of electrically excitable membranes to current injection is asymmetric. In the model cell (Figure 2) the membrane can be either active or passive. First make sure it is passive. Then, examine the effect of injecting hyperpolarizing and depolarizing currents. The response is always linear, as seen previously with a parallel RC circuit.

Figure 2 Electrically excitable model cell. Press the ‘–’ and ‘+’ buttons to inject hyperpolarizing or depolarizing currents into the cell. Switch between ‘passive’ and ‘active’ membrane properties with the buttons. The membrane potential (top panel), and the injected current stimulus (bottom panel) are shown.

Now change the membrane type to ‘active’. Note that no matter how large the hyperpolarizing current is made only a linear passive response is evoked. In contrast, for depolarizing currents there is a ‘threshold’ for triggering an action potential. Depolarizing currents invariably trigger an action potential once they reach a certain threshold size.

The action potential response is ‘all-or-none’, meaning that the height and duration of the action potential do not change significantly as the suprathreshold currents increase in size. A commonly used analogy is the firing of a pistol. The response is independent of how hard the trigger is pulled.

The physiologically important stimulus triggering an action potential in neurons or muscle cells is also a depolarizing current. Physiological stimuli include local circuit current flow from an action potential firing in another region of the cell, excitatory synaptic input from a pre-synaptic cell, or sensation activated currents in sensory cells.

Refractory Period

Following the firing of an action potential there is a period, known as the refractory period, during which the membrane is less excitable (Figure 3).

Figure 3 Electrically excitable model cell. The absolute and relative refractory periods are indicated. Press the ‘–’ and ‘+’ buttons to change the delay between the first and second stimuli.

In this simulation there are two stimuli that trigger two action potentials. The second stimulus is delivered after a variable delay. In this model cell a threshold stimulus is 0.6 nA and initially both stimuli are set to this value. Slowly reduce the delay between the first and second stimuli until the second action potential no longer fires. The second stimulus is now in the relative refractory period. In this period, it is still possible to trigger an action potential by increasing the stimulus current.

Continue to reduce the delay and increase the stimulus. At first only small increases in current are needed but as the delay gets close to the absolute refractory period the threshold current becomes relatively large. In this simulation the maximum current that can be applied is 5 times the threshold stimulus or 3 nA. In real life there is obviously a practical limit to how large the current can be before you simply fry the cell. In the absolute refractory period even this relatively large current can no longer trigger an action potential.

Mechanisms

To move beyond a phenomenological understanding of the action potential it is necessary to have a detailed understanding of the function of voltage-gated ion channels. There are several questions to be addressed:

How do ion channels mediate the movement of ions across the membrane rapidly enough to produce the relatively large currents during the rising phase of the action potential?
How do the channels facilitate the selective movement of either sodium or potassium ions to create the opposing currents necessary to depolarize and then repolarize the membrane potential?
How are the channels activated by membrane voltage depolarizations?
How do the channels become inactive following an action potential, resulting in a refractory period?

Action potentials are the primary means by which information is transmitted between neurons within the brain and between the brain and the body. A detailed understanding of action potential function is central to any understanding of nervous system function.

References

1. Piccolino, M. Luigi Galvani and animal electricity: two centuries after the foundation of electrophysiology. Trends in Neurosciences 20, 443–448 (1997).

2. Schuetze, S.M. The discovery of the action potential. Trends in Neurosciences 6, 164–168 (1983).

3. Hodgkin, A. L. & Huxley, A. F. A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol 117, 500–544 (1952).