Fundamental Neuroscience, Third Edition

The communication of information between neurons and between neurons and muscles or peripheral organs requires that signals travel over considerable distances. A number of notable scientists have contemplated the nature of this communication through the ages. In the second century ad, the great Greek physician Claudius Galen proposed that “humors” fl owed from the brain to the muscles along hollow nerves. A true electrophysiological understanding of nerve and muscle, however, depended on the discovery and understanding of electricity itself. The precise nature of nerve and muscle action became clearer with the advent of new experimental techniques by a number of European scientists, including Luigi Galvini, Emil Du Bois-Reymond, Carlo Matteucci, and Hermann von Helmholtz, to name a few (Brazier, 1988). Through the application of electrical stimulation to nerves and muscles, these early electrophysiologists demonstrated that the conduction of commands from the brain to the muscle for the generation of movement was mediated by the fl ow of electricity along nerve fi bers. With the advancement of electrophysiological techniques, electrical activity recorded from nerves revealed that the conduction of information along the axon was mediated by the active generation of an electrical potential, called the action potential. But what precisely was the nature of these action potentials? To know this in detail required not only a preparation from which to obtain intracellular recordings but also one that could survive in vitro. The squid giant axon provided precisely such a preparation. Many invertebrates contain unusually large axons for the generation of escape refl exes; large axons conduct more quickly than small ones and so the response time for escape is reduced (see Chapter 5). The squid possesses an axon approximately 0.5 mm in diameter, large enough to be impaled by even a course micropipette (Fig. 6.1). By inserting a glass micropipette fi lled with a salt solution into the squid giant axon, Alan Hodgkin and Andrew Huxley demonstrated in 1939 that axons at rest are electrically polarized, exhibiting a resting membrane potential of approximately −60 mV inside versus outside. In the generation of an action potential, the polarization of the membrane is removed (referred to as depolarization) and exhibits a rapid swing toward, and even past, 0 mV (Fig. 6.1). This depolarization is followed by a rapid swing in the membrane potential to more negative values, a process referred to as hyperpolarization. The membrane potential following an action potential typically becomes even more negative than the original value of approximately −60 mV. This period of increased polarization is referred to as the after-hyperpolarization or the undershoot. The development of electrophysiological techniques to the point that intracellular recordings could be obtained from the small cells of the mammalian nervous system revealed that action potentials in these neurons are generated through mechanisms similar to that of the squid giant axon. It is now known that action potential generation in nearly all types of neurons and muscle cells is accomplished through mechanisms similar to those fi rst detailed in the squid giant axon by Hodgkin and Huxley. This chapter considers the cellular mechanisms by which neurons and axons generate a resting membrane potential and how this membrane potential briefl y is disrupted for the purpose of propagation of an electrical signal, the action potential.