What Are Action Potentials

Electrically excitable cells share in common the ability to generate APs. During an AP, the membrane potential (MP) of an electrically excitable cell displays dramatic, stereotypic, and rapid changes. In muscle cells, AP generation quickly leads to muscle contraction. In neurons, APs allow rapid intra- and intercellular communication.

The classic work of Hodgkin and Huxley (1952; Hodgkin, 1958, 1964) demonstrated that time-dependent changes in the membrane conductance to specific ions underlie the generation of APs. For more detailed treatment of the ionic basis of the MP and AP, we refer the reader to any of several excellent books (Jack et al., 1988; Johnston and Wu, 1994; Kandel et al., 2000; Hille, 2001; Nicholls et al., 2001). Below, we briefly review key aspects of AP generation. We have defined important terms in the glossary for readers who wish to read the primary literature.

Typically, all cells display an electrical difference across their membrane. This electrical difference, known as the MP, has values in the mV range. By convention, the inside of the cell is negative with respect to the outside. The predominant value of the MP is referred to as the resting MP (RMP).

Excitable cells generate APs (also referred to as spikes or impulses) in response to stimuli that bring the MP to a new, less negative value, known as threshold. Threshold values are not fixed and vary among excitable cells. Moreover, for any given cell, the value of threshold can change over time as a result of developmental regulation, activity, or cell-cell interactions. Stimuli that bring the MP to values less positive than threshold do not lead to AP generation and instead generate subthreshold responses. Thus, APs are not generated in a graded manner but rather as an all-or-none response of the membrane to stimuli of sufficient intensity (Hodgkin and Huxley, 1952).

Once threshold is achieved, the conductance to sodium and/or calcium ions increases, allowing rapid entry of positively charged sodium and/or calcium ions. The influx of positive charge results in a more positive MP. With further depolarization, more sodium channels open, resulting in greater sodium influx and even more positive MP values. When depolarization occurs, the membrane conductance to potassium ions also increases, but with a delay. The increased potassium conductance and inactivation of sodium channels repolarize the membrane to its original negative resting value, thereby terminating the AP.

In neurons, AP generation initiates near the cell body at a site known as the axon hillock (Coombs et al., 1957a, 1957b). Subsequently, APs propagate down the axon at constant velocity and amplitude. The ability to propagate APs without diminution in amplitude is an essential feature of neuronal cell-cell communication and guarantees that signals will be transmitted faithfully without failure.

1.13.2.1 APs are Neuronal Signatures

Figure 1 presents an example of an AP fired by a mature neuron. Typically, adult neurons fire APs that are brief in duration and rely upon voltage-gated sodium channels for generation. However, APs fired by mature neurons vary significantly. Further, some neurons respond to stimulation by firing a single AP, while others fire multiple impulses in a characteristic pattern. Consequently, the type of AP or AP train fired in response to stimulation can serve as a signature of neuronal identity (for review, see Contreras, 2004).

1.13.2.2 AP Waveform Properties

The plot of the MP as a function of time during an AP is known as the AP waveform (Figure 1). Characterization of APs involves analysis of specific properties of the waveform that, in turn, reflect the complement of voltage-gated channels expressed by the cell (see 'Glossary').

During the AP, the MP achieves positive values near the equilibrium potential for sodium. The most positive MP achieved during an AP is known as the peak. The rapid depolarization leading to the peak reflects the activity of voltage-gated sodium channels. Thus, measuring the rate of rise provides an indication of sodium current density. In contrast, the activity of voltage-gated potassium channels contributes to the subsequent repolarization and the rate of fall.

After repolarization, the MP often becomes slightly more negative than the standard RMP,

Activation

Amplitude (mV)

Repolarization (mV)

Activation mV

Repolarization (mV)

Overshoot (ms)

Afterhyperpolarization

2 ms

Figure 1 Stereotypic AP of a mature neuron: an AP recorded from a Rohon-Beard cell of a 2-day-old zebra fish embryo is shown (Pineda and Ribera, unpublished data). Several AP properties that are defined in 'Glossary' are illustrated in the figure.

Overshoot (ms)

Threshold (mV)

Duration (ms)

Duration (ms)

Afterhyperpolarization

2 ms

Figure 1 Stereotypic AP of a mature neuron: an AP recorded from a Rohon-Beard cell of a 2-day-old zebra fish embryo is shown (Pineda and Ribera, unpublished data). Several AP properties that are defined in 'Glossary' are illustrated in the figure.

resulting in an afterhyperpolarization. Afterhyper-polarizations play important roles in determining the frequency of AP firing. Because information is often encoded by AP frequency, afterhyperpolariza-tions can greatly influence processing of information in the nervous system.

One property of APs that varies greatly between excitable cells is the duration. In some neurons, the AP duration is extremely brief and barely 1 ms (Storm, 1987). In contrast, skeletal muscle fibers fire APs that have slightly longer durations (~5-10 ms; Kuriyama et al., 1970). Cardiac myocytes fire strikingly different impulses with durations that are often as long as 500 ms (Cavalie et al., 1985; Hume and Uehara, 1985). As discussed further below, the duration of neuronal APs often undergoes substantial developmental regulation.

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