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The action potential in mammalian central neurons
Bruce P. Bean

Abstract | The action potential of the squid giant axon is formed by just two voltagedependent conductances in the cell membrane, yet mammalian central neurons typically express more than a dozen different types of voltage-dependent ion channels. This rich repertoire of channels allows neurons to encode information bygenerating action potentials with a wide range of shapes, frequencies and patterns. Recent work offers an increasingly detailed understanding of how the expression of particular channel types underlies the remarkably diverse firing behaviour of various types of neurons.
Heterologous expression
Expression of protein molecules by the injection of complementary RNA into the cytoplasm (orcomplementary DNA into the nucleus) of host cells that do not normally express the proteins, such as Xenopus oocytes or mammalian cell lines.

Spike
Another term for an action potential (especially the portion with the most rapidly changing voltage).

Harvard Medical School, Department of Neurobiology, 220 Longwood Avenue, Boston, Massachusetts 02115, USA. e-mail: bruce_bean@hms. harvard.edudoi:10.1038/nrn2148

In the years since the Hodgkin–Huxley analysis of the squid axon action potential1, it has become clear that most neurons contain far more than the two voltagedependent conductances found in the squid axon2,3. Action potentials serve a very different function in neuronal cell bodies, where they encode information in their frequency and pattern, than in axons, where they serveprimarily to rapidly propagate signals over distance. The membrane of the squid axon is a poor encoder, as it fires only over a narrow range of frequencies when stimulated by the injection of widely-varying current levels4. By contrast, most neuronal cell bodies (in both vertebrate and invertebrate animals) can fire over a far wider range of frequencies and can respond to small changes in input currentswith significant changes in firing frequency5–10. Clearly, this richer firing behaviour depends on the expression of more types of voltage-dependent ion channels. Interestingly, although the squid axon is strikingly deficient as an encoder, some other invertebrate axons can fire over a wide frequency range11 and have a richer repertoire of ion channel types12, as do at least some mammalian axons13.The presence of multiple channel types in most neurons has been appreciated since at least the 1970s. However, few were prepared for the staggering number of distinct kinds of ion channels revealed over the last two decades by the convergent techniques of patchclamp recording, heterologous expression of cloned channels and genomic analysis — including, for example, more than 100 principalsubunits of potassium channels14. Even more surprising, perhaps, was the gradual realization of just how many distinct voltage-dependent conductances are expressed by individual neurons in the mammalian brain — commonly including 2 or 3 components of sodium current, 4 or 5 different

components of voltage-dependent calcium currents, at least 4 or 5 different components of voltage-activated potassiumcurrent, at least 2 to 3 types of calcium-activated potassium currents, the hyperpolarization-activated current Ih, and others. Because of this complexity, our understanding of how different conductances interact to form the action potentials of even the best-studied central neurons is still incomplete, even though Hodgkin and Huxley devised the basic experimental approach still being used —voltage-clamp analysis of individual timeand voltage-dependent conductances and reconstruction of the whole by numerical modelling — more than half a century ago1. In this review I discuss differences in the shape, rate and pattern of firing of action potentials between various types of neurons, focusing on mammalian central neurons, and review recent advances in understanding the role of specific...