Nerve Physiology
The resting potential and action potentials in single axons are described in detail earlier. Here, we focus on the physiology of whole nerve trunks. The function of the axons is to carry information in the form of electrical activity from one area to another. A measure of the ability of a nerve to perform this function would be of major clinical value in the identification of disease involving a nerve. However, during normal function, the electrical activities of the fibers in a nerve are asynchronous and cancel each other out.
Nerves are the gross structures carrying motor, sensory, and autonomic axons to the end organs. (Some nerves contain only autonomic fibers, e.g., the vagus nerve.) Nerves, whether peripheral or spinal, are made up of the axons traveling between the central nervous system and the peripheral end organ. They are similar in their microscopic features, their physiology, and their pathophysiologic alterations with disease. The general features that are common to all types of nerves are considered first and the differences considered subsequently. A nerve is composed of thousands of axons ranging in size from less than 1 to 20 mm in diameter.Nerves are made up of afferent and efferent fibers. The axons can be differentiated histologically on the basis of their size and the presence or absence of myelin. The unmyelinated fibers are small and include autonomic fibers and fibers carrying pain and temperature. Proprioceptive and somatic motor fibers are large.
Notice that the largest and fastest fibers elicit larger action potentials. the fibers are subdivided into subgroups labeled with Greek letter having successively higher stimulation thresholds and slower conduction velocities.
Communication between different parts of the nervous system depends on the propagation of nerve impulse (action potentials) along the axons of neurons. Although the electrical nature of impulses was recognized over a century ago, it was the invention and application of the oscilloscope that accelerated the development of modern neurophysiology.
The compound action potential is the propagated impulse in each axon and is an all or none even arising from the potential change across the cell membrane. When we record from the surface of the nerve bundle, we are not recording changes across the cell membranes; we are recording the potential drop produced by local currents flowing along the outside of the active fibers. The compound action potential recording represents the summed activity of the individual axons and thus depends on the number of axons conducting, their relative sizes, and their conduction velocities. Larger axons can generate larger extracellular currents since membrane current increases in proportion to membrane area. Thus, due to amplitude differences and different conduction velocities, different fiber groups can be distinguished in our recordings.
Excitability, therefore, depends on axon size. The excitability of a nerve can be defined in terms of the two variables of a stimulus voltage and duration. If the strength of the current (or voltage) is plotted against the duration of a stimulus needed to produce excitation of a nerve, a curve is obtained, which is called a strength duration curve. A shift in the strength duration curve indicates a change in excitability and is seen in nerve diseases. The strength duration curve is often characterized in terms of two points. The rheobase is the minimal voltage needed to produce excitation with a long stimulus duration (usually 300 ms) and the chronaxie is the time required to excite a nerve by a stimulus with a voltage twice as large as the rheobase (Fig. 26). The compound action potential recorded from a nerve trunk after supramaximal stimulation is the summation of action potentials from many axons. Its amplitude can be graded by varying the strength of the stimulus. A threshold stimulus evokes only a small potential resulting from activity in a few large fibers. As the stimulus strength is increased, more fibers are excited, and their activity is added to the compound action potential as each additionally activated fiber produces a small increment in the recorded voltage.
The action potential of a single axon can be recorded experimentally with an intracellular microelectrode, which records the action potential as a monophasic wave of depolarization. The electrical activity in a single nerve fiber also can be monitored by placing electrodes in the extracellular fluid close to the nerve fiber. This method does not detect transmembrane potential changes; rather, it senses potential changes in the extracellular fluid that result from longitudinal current flow between the depolarized and nondepolarized regions of the axon. The extracellular recording is improved (a bigger voltage change is measured) if the extracellular resistance is artificially increased by recording from the nerve experimentally in air or in oil. Extracellular recording from single axons is difficult because of their small size; however, it is possible to record from groups of axons or from whole nerve trunks, if all axons discharge synchronously. This recording is obtained experimentally and from patients by applying an electrical shock that activates all axons simultaneously. The potential recorded from a nerve activated in this way is the compound action potential.
The configuration of the signal obtained from an extracellular recording of the nerve impulse depends on the electrode arrangement. A monophasic potential change is observed from nerve fibers con- ducting an impulse if only one of the electrodes is placed over an active nerve. A biphasic potential is recorded if both electrodes are placed over the active nerve (Fig. 25). As in the stimulation of a single axon, the whole nerve trunk is activated by passing a current between the cathode (negative pole) and the anode (positive pole). The cathode depolarizes the underlying axons, and the anode hyperpolarizes them. Depolarization requires current flow inside the axons. Because large axons have lower internal resistance, the threshold for activation is lowest for the larger fibers. The threshold stimulus for a nerve trunk is that which just excites the large fibers. Supramaximal stimuli activate all fibers, including the small fibers, and require greater current flow.
When all the fibers are excited, the amplitude of the compound action potential is maximum; it will not increase in amplitude with further increases in the stimulus strength (supramaximal). The compound action potential thus can be graded in amplitude, while action potentials in single axons are not graded but fire in an all-or-none fashion. Variation in axon diam- eter in a nerve trunk results in different conduction velocities as well as different thresholds for activation. The rate at which an axon conducts is a function of the amount of longitudinal current flow and is greater with larger axons. The conduction velocity is calculated by dividing the distance a potential travels by the time it takes to travel that distance. It is approximately five times the axon’s diameter in microns, for example, 5–100 m/s for axons of 1–20 mm diameter. If a nerve trunk is stimulated at a distance from the recording electrodes, the compound action potential exhibits several components (Fig. 27) because of the dispersion of the potentials from fibers of different diameters. The impulses in the large fibers reach the recording site first. The components of the com- pound action potential thus distinguish activity in groups of fibers whose diameters are within certain size ranges. The afferent fibers in cutaneous nerves (to joints and skin) are subdivided into groups named
Because the function of peripheral nerves is to conduct action potentials from one area to another, three general kinds of functional abnormality occur.
A second important manifestation is the result of the loss of trophic factors of the nerve acting on muscle. A denervated muscle atrophies and undergoes change in its membrane. This change includes a hypersensitivity to acetylcholine. Normally, most of the acetylcholine receptors are confined to the area immediately adjacent to the end plate. After denervation, the receptors spread along the surface, until the entire fiber responds to the drug. This is one form of denervation hypersensitivity. Muscle fibers undergo denervation hypersensitivity and begin to discharge and twitch approximately two weeks after losing their innervation. Such spontaneous, regular twitching of single muscle fibers is called fibrillation. Transient alterations in the physiology of the cells cause transient symptoms and signs.
Nerves are the gross structures carrying motor, sensory, and autonomic axons to the end organs. (Some nerves contain only autonomic fibers, e.g., the vagus nerve.) Nerves, whether peripheral or spinal, are made up of the axons traveling between the central nervous system and the peripheral end organ. They are similar in their microscopic features, their physiology, and their pathophysiologic alterations with disease. The general features that are common to all types of nerves are considered first and the differences considered subsequently. A nerve is composed of thousands of axons ranging in size from less than 1 to 20 mm in diameter.Nerves are made up of afferent and efferent fibers. The axons can be differentiated histologically on the basis of their size and the presence or absence of myelin. The unmyelinated fibers are small and include autonomic fibers and fibers carrying pain and temperature. Proprioceptive and somatic motor fibers are large.
Notice that the largest and fastest fibers elicit larger action potentials. the fibers are subdivided into subgroups labeled with Greek letter having successively higher stimulation thresholds and slower conduction velocities.
Communication between different parts of the nervous system depends on the propagation of nerve impulse (action potentials) along the axons of neurons. Although the electrical nature of impulses was recognized over a century ago, it was the invention and application of the oscilloscope that accelerated the development of modern neurophysiology.
The compound action potential is the propagated impulse in each axon and is an all or none even arising from the potential change across the cell membrane. When we record from the surface of the nerve bundle, we are not recording changes across the cell membranes; we are recording the potential drop produced by local currents flowing along the outside of the active fibers. The compound action potential recording represents the summed activity of the individual axons and thus depends on the number of axons conducting, their relative sizes, and their conduction velocities. Larger axons can generate larger extracellular currents since membrane current increases in proportion to membrane area. Thus, due to amplitude differences and different conduction velocities, different fiber groups can be distinguished in our recordings.
Excitability, therefore, depends on axon size. The excitability of a nerve can be defined in terms of the two variables of a stimulus voltage and duration. If the strength of the current (or voltage) is plotted against the duration of a stimulus needed to produce excitation of a nerve, a curve is obtained, which is called a strength duration curve. A shift in the strength duration curve indicates a change in excitability and is seen in nerve diseases. The strength duration curve is often characterized in terms of two points. The rheobase is the minimal voltage needed to produce excitation with a long stimulus duration (usually 300 ms) and the chronaxie is the time required to excite a nerve by a stimulus with a voltage twice as large as the rheobase (Fig. 26). The compound action potential recorded from a nerve trunk after supramaximal stimulation is the summation of action potentials from many axons. Its amplitude can be graded by varying the strength of the stimulus. A threshold stimulus evokes only a small potential resulting from activity in a few large fibers. As the stimulus strength is increased, more fibers are excited, and their activity is added to the compound action potential as each additionally activated fiber produces a small increment in the recorded voltage.
The action potential of a single axon can be recorded experimentally with an intracellular microelectrode, which records the action potential as a monophasic wave of depolarization. The electrical activity in a single nerve fiber also can be monitored by placing electrodes in the extracellular fluid close to the nerve fiber. This method does not detect transmembrane potential changes; rather, it senses potential changes in the extracellular fluid that result from longitudinal current flow between the depolarized and nondepolarized regions of the axon. The extracellular recording is improved (a bigger voltage change is measured) if the extracellular resistance is artificially increased by recording from the nerve experimentally in air or in oil. Extracellular recording from single axons is difficult because of their small size; however, it is possible to record from groups of axons or from whole nerve trunks, if all axons discharge synchronously. This recording is obtained experimentally and from patients by applying an electrical shock that activates all axons simultaneously. The potential recorded from a nerve activated in this way is the compound action potential.
The configuration of the signal obtained from an extracellular recording of the nerve impulse depends on the electrode arrangement. A monophasic potential change is observed from nerve fibers con- ducting an impulse if only one of the electrodes is placed over an active nerve. A biphasic potential is recorded if both electrodes are placed over the active nerve (Fig. 25). As in the stimulation of a single axon, the whole nerve trunk is activated by passing a current between the cathode (negative pole) and the anode (positive pole). The cathode depolarizes the underlying axons, and the anode hyperpolarizes them. Depolarization requires current flow inside the axons. Because large axons have lower internal resistance, the threshold for activation is lowest for the larger fibers. The threshold stimulus for a nerve trunk is that which just excites the large fibers. Supramaximal stimuli activate all fibers, including the small fibers, and require greater current flow.
When all the fibers are excited, the amplitude of the compound action potential is maximum; it will not increase in amplitude with further increases in the stimulus strength (supramaximal). The compound action potential thus can be graded in amplitude, while action potentials in single axons are not graded but fire in an all-or-none fashion. Variation in axon diam- eter in a nerve trunk results in different conduction velocities as well as different thresholds for activation. The rate at which an axon conducts is a function of the amount of longitudinal current flow and is greater with larger axons. The conduction velocity is calculated by dividing the distance a potential travels by the time it takes to travel that distance. It is approximately five times the axon’s diameter in microns, for example, 5–100 m/s for axons of 1–20 mm diameter. If a nerve trunk is stimulated at a distance from the recording electrodes, the compound action potential exhibits several components (Fig. 27) because of the dispersion of the potentials from fibers of different diameters. The impulses in the large fibers reach the recording site first. The components of the com- pound action potential thus distinguish activity in groups of fibers whose diameters are within certain size ranges. The afferent fibers in cutaneous nerves (to joints and skin) are subdivided into groups named
Because the function of peripheral nerves is to conduct action potentials from one area to another, three general kinds of functional abnormality occur.
- (1) The excitability of axons may be increased with spontaneous or excessive firing of an axon. This occurs in many disorders, but especially in ischemic or metabolic diseases.
- (2) The axon may be unable to conduct an action potential, because of either transient metabolic changes or structural damage to the axon. If an axon is severed, the distal portion undergoes wallerian degeneration but is able to conduct an impulse in the distal part of the nerve for 3– 5 days. The proximal portion of the axon continues to function normally.
- (3) The axon may conduct an impulse slowly or at low rates of firing. This may occur from loss of myelin or be due to narrowing and deformation of the axon. The latter may be seen in the area of compression or in regenerating fibers. Slow conduction results in mild clinical symptoms or signs except for the ability to carry high-frequency information such as vibration, which is severely impaired.
A second important manifestation is the result of the loss of trophic factors of the nerve acting on muscle. A denervated muscle atrophies and undergoes change in its membrane. This change includes a hypersensitivity to acetylcholine. Normally, most of the acetylcholine receptors are confined to the area immediately adjacent to the end plate. After denervation, the receptors spread along the surface, until the entire fiber responds to the drug. This is one form of denervation hypersensitivity. Muscle fibers undergo denervation hypersensitivity and begin to discharge and twitch approximately two weeks after losing their innervation. Such spontaneous, regular twitching of single muscle fibers is called fibrillation. Transient alterations in the physiology of the cells cause transient symptoms and signs.