Structure and Function of Muscle Fibers and Motor Units
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Cambridge University Press 978-0-521-87629-2 - Disorders of Voluntary Muscle, Eighth Edition Edited by George Karpati, David Hilton-Jones, Kate Bushby and Robert C. Griggs Excerpt More information Section 1 The scientific basis of muscle disease Chapter Structure and function of muscle fibers 1 and motor units Mary Kay Floeter Introduction Anatomy of motor units The term “motor unit” was introduced by Sir Charles Sherrington, a founder of modern neurophysiology, who Motor neurons observed that force occurred in discrete steps when a muscle Motor neurons are the only central neurons with axons that contracted in the stretch reflex [1]. He postulated that each leave the central nervous system (CNS) to innervate non- step was produced by the all-or-none action of a single neuronal tissue. Their cell bodies are located in the anterior motor neuron upon the muscle fibers it innervated. Sher- horn of the gray matter of the spinal cord (Figure 1.1). The rington’s concept of the motor unit assumed that each motor neurons that innervate the same muscle cluster together muscle fiber receives innervation from only one motor in motor nuclei that form elongated columns that generally neuron, and that the muscle fiber faithfully responds to every extend over several spinal cord segments [3]. The number of impulse of the motor neuron. These assumptions have sub- motor neurons innervating each muscles varies, ranging from sequently been shown to be true in healthy adult skeletal the estimates of 30–40 motor neurons innervating the delicate muscles. The motor unit has become a fundamental concept tenuissimus muscle in the cat [4] to estimates of 100–200 in understanding the physiology of muscle and the control of motor neurons innervating human thenar muscles [5, 6]. In movement. the lumbar and cervical enlargements of the spinal cord, the A motor unit consists of one motor neuron and all the motor neurons that innervate distal limb muscles are located muscle fibers it innervates. The term muscle unit has been most laterally within the anterior horn, and motor neurons introduced to refer to the group of muscle fibers innervated innervating proximal muscles lie more medially [7, 8]. The by a given motor neuron [2]. The motor neuron and its axons of motor neurons exit the spinal cord through the muscle unit are inseparable in function because each action adjacent anterior roots. When motor axons innervating the potential in the neuron activates all fibers of the muscle unit. same muscle exit from roots of several segments, they rejoin in Thus motor units are the indivisible quantal elements in all a muscle nerve after traversing peripheral plexuses and nerve movements. The electrophysiological, metabolic, mechanical, trunks. The muscle nerve contains motor axons innervating and anatomical properties of the motor neuron and its the muscle and the sensory axons arising from receptors muscle unit are coordinated in a manner that allows efficient within the muscle, such as the muscle spindles and tendon muscle contraction over a wide range of motor behaviors. organs. The coordinated expression of the proteins that govern these In mammals, there are three kinds of motor neurons in the properties reflects the interplay between the trophic control motor nucleus. Alpha motor neurons are large cells [9, 10] that that motor neurons exert over their muscle fibers through innervate the striated muscle fibers that make up the bulk of activity patterns and chemical trophic factors, as well as skeletal muscle tissue (extrafusal fibers). Gamma, or fusimotor, trophic feedback from the muscle fiber to the motor neuron. neurons are considerably smaller [11] and exclusively innerv- Although most of the properties of a given motor unit ate one or more of the three types of specialized muscle fibers become specified during the early postnatal period of devel- within the muscle spindle – stretch receptor organs that are opment, physical activity and disease processes can modify present in virtually all somatic muscles [12, 13]. A third class of certain properties to a limited extent. In this chapter, the motor neuron, called skeleto-fusimotor or beta motor basic structural and physiological properties of motor units neurons, innervates both intra- and extrafusal muscle fibers and muscle fibers will be introduced, with a particular [14]. Beta motor neurons have been found in higher primates emphasis on humans and other mammals. [15] and probably also occur in humans. Because beta motor Disorders of Voluntary Muscle, 8th edn., eds. George Karpati, David Hilton-Jones, Kate Bushby and Robert C. Griggs. Published by Cambridge University Press. # Cambridge University Press 2010. 1 © in this web service Cambridge University Press www.cambridge.org Cambridge University Press 978-0-521-87629-2 - Disorders of Voluntary Muscle, Eighth Edition Edited by George Karpati, David Hilton-Jones, Kate Bushby and Robert C. Griggs Excerpt More information Section 1: The scientific basis of muscle disease neurons are difficult to identify in physiological experiments, there is little direct evidence about their properties. What little is known indicates that the properties of beta motor neurons and their extrafusal muscle fibers are essentially the same as those of alpha motor neurons [16]. For this reason, alpha and beta motor neurons will not be distinguished in this chapter. Alpha motor neurons have extensive dendritic trees that receive synaptic input over their entire extent [17, 18, 19]. Their myelinated axons have large diameters with correspon- dingly fast conducting velocities, ranging from 40 to 60 m/s in human motor nerves [20]. Faster conduction velocities, 50–120 m/s, have been reported in cats and smaller mammals [21]. The axons of motor neurons can be extremely long, up to a meter in length for those motor neurons innervating the distal foot muscles of a tall adult. The length and diameter of the motor axons mean that the volume of axoplasm may exceed the volume in the cell body and dendrites by tenfold or more (Figure 1.2). The large metabolic demands of maintain- ing the peripheral axon presumably account for the large size of the motor neuron cell body. Figure 1.1. Cross-section of the lumbar spinal cord, showing the location of the motor neuron pools. Volume Motor neuron (soma 50 µm diameter) 4 × 105 µm3 Motor neuron Motor axon (14 µm × 13 cm) 2 × 106 µm3 Muscle fiber (50 µm × 2 cm) 4 × 107 µm3 9 mm more Muscle unit (100 fibers) 4 × 109 µm3 1mm Axon Muscle unit 9 mm more Figure 1.2. Diagram of a motor unit with its components drawn to scale. Note the smaller size of the motor neuron cell body compared with its extensive dendritic tree and very long motor axon. The volume of a single muscle fiber is more than tenfold greater than the volume of cytoplasm in the motor neuron plus its axon. Contributed by R. E. Burke. 2 © in this web service Cambridge University Press www.cambridge.org Cambridge University Press 978-0-521-87629-2 - Disorders of Voluntary Muscle, Eighth Edition Edited by George Karpati, David Hilton-Jones, Kate Bushby and Robert C. Griggs Excerpt More information Chapter 1: Muscle fibers and motor units Neuromuscular junctions voltage-gated calcium channels on T-tubule membranes and the calcium release proteins, known as ryanodine receptors, on As the myelinated motor axons near their target muscle, they the SR membrane [30]. begin to divide into tens or hundreds of terminal branches, The contractile apparatus of the muscle is organized into a which lose their myelin sheaths as they near the neuromuscu- series of repeated units a few microns long called sarcomeres lar junctions (NMJs). The NMJ is a large, highly specialized [31]. The sarcomere is the smallest unit of contraction. It synapse between the motor nerve terminal and the muscle consists of highly organized protein assemblies that give the fiber [22]. In somatic muscles there is only one NMJ per muscle fiber a characteristic striated appearance (Figure 1.4b). muscle fiber [23], but exceptions are found in some cranial The sarcomere contains the myofibrils, longitudinal arrays of muscles, such as the laryngeal [24] and extraocular muscles thick and thin filaments that are maintained in a hexagonal [25]. On a given muscle fiber, the NMJ is located approxi- lattice by a scaffolding network (Figure 1.4a). Proteins in the mately equidistant from its ends, allowing action potential scaffolding network condense at the ends and middle of depolarization to spread equally to both ends from the center the sarcomere to form transverse bands called Z-disks and of the muscle fiber. The NMJ is a complex structure that M-bands [32]. The thin filaments consist of filamentous actin undergoes remodeling during development and aging and in entwined by tropomyosin and troponin, a calcium-binding response to denervation. At the NMJ, the motor nerve ter- protein. Thick filaments consist of myosin, a large molecule minal is separated from the postsynaptic muscle membrane by with heavy and light chains. The myosin heavy chains have a a synaptic space containing basal lamina with synapse-specific tail region and a globular head. Thick filaments are formed by glycoproteins. On the postsynaptic side, the muscle membrane the assembly of myosin monomers with their tails centrally is highly folded. Acetylcholine receptors are found on the and heads protruding outwards, with an antiparallel orienta- crests of the junctional folds apposing the vesicle release sites tion on opposite ends of the filament. Z-disks, which mark the on the presynaptic terminal, whereas the voltage-gated sodium border between sarcomeres, serve to anchor the thin filaments. channels responsible for action potential generation are dens- The Z-disks are formed by an ensemble of several proteins, est in the depths of the folds [26]. NMJs exhibit structural including alpha-actinin.