Neuromuscular Function and Disorders

Alan J. McComas

• Publisher: Butterworth-Heinemann
• Year: 2013
• ISBN:
  9781483163062
• Topic: Medicine
• Subtopic: Diseases & Allergies

Neuromuscular Function and Disorders focuses on the various processes underlying disordered neuromuscular function. Topics covered include the nature of membrane defects in myotonia and familial periodic paralysis; the disorder of neuromuscular transmission responsible for myasthenia gravis and the various pseudo-myasthenic syndromes; and the disorders of Schwann cell function which cause demyelination. This book is comprised of 28 chapters divided into two sections and begins with a discussion on the normal anatomy and physiology of peripheral nerve and muscle. Included in the first section are descriptions of the ionic mechanisms responsible for the resting and action potentials of nerve and muscle; the sequential stages in neuromuscular transmission; excitation-contraction coupling; the sliding filament mechanism of myofibrillar shortening; and the morphological and functional properties of motor units. The neurophysiology of exercise and muscle fatigue is also considered, along with the nature of the trophic influences exerted by the motoneuron and muscle fiber upon each other. The second half of the book deals entirely with various diseases of peripheral nerve and muscle, together with diagnostic procedures and therapeutic management. A consistent theme in this section is the recognition of neural abnormalities in diseases hitherto considered as primary disorders of the muscle fiber. This monograph should be of value to neurologists, medical students, research workers, and students and research scientists in physiology, zoology, pharmacology, kinesiology, and physical education.

PART 1

MUSCLE FIBRES AND MOTONEURONES

Outline

Chapter 1: THE MUSCLE FIBRE

Chapter 2: THE MOTONEURONE AND ITS AXON

Chapter 3: RESTING AND ACTION POTENTIALS

Chapter 4: THE NEUROMUSCULAR JUNCTION

Chapter 5: MUSCLE CONTRACTION

Chapter 6: MOTOR UNITS

Chapter 7: EXERCISE AND FATIGUE

Chapter 8: TROPHIC INTERACTIONS OF NERVE AND MUSCLE: DENERVATION AND REINNERVATION

Chapter 9: USE AND DISUSE

Chapter 10: TROPHIC INFLUENCE OF MUSCLE ON NERVE

Chapter 11: MUSCLE GROWTH

Chapter 12: AGEING

Chapter 1

THE MUSCLE FIBRE

Publisher Summary

This chapter discusses the structure of muscle fiber. Voluntary” muscles are composed of two types of muscle fibers. By far the most common are those fibers that make up nearly the entire bulk of the muscle and are described as extrafusal. This term distinguishes them from the much smaller muscle fibers that are found inside the muscle spindles. Because of their location, these smaller muscle fibers are referred to as intrafusal. At birth, human fibers are slender, measuring about 10–20 μm in diameter. Throughout childhood and particularly during the growth spurt in puberty, the sizes increase and eventually attain adult dimensions with most diameters in the 40–80 μm range. The membrane of the muscle fiber is termed the sarcolemma and is some 75 A thick. Just outside the sarcolemma and clearly visible in electronmicrographs is the basement membrane which is composed of proteins and polysaccharides. Each muscle fiber contains numerous nuclei which are dispersed along the inner surface of the sarcolemma, particularly in the region of the motor end-plate. The most obvious structures within the muscle fiber are the myofibrils, which are the units responsible for contraction and relaxation of the fiber.

The ‘voluntary’ muscles are composed of muscle fibres, of which two types are found. By far the commonest are those fibres which make up nearly all the bulk of the muscle and are described as extrafusal. This term distinguishes them from the much smaller muscle fibres which are found inside the muscle spindles; because of their location these last fibres are referred to as intrafusal. The special structure and function of the intrafusal fibres are of considerable interest and have been reviewed elsewhere (Matthews, 1972). This book will deal only with the extrafusal muscle fibres, however, for it is these fibres about which most is known in disease and it is their ineffectiveness which is ultimately responsible for the cardinal symptom of weakness.

NUMBERS AND SIZES OF MUSCLE FIBRES

Because of the time-consuming nature of the task involved, there are very few values for the numbers of extrafusal fibres in human voluntary muscles. On the basis of fibre counts in samples taken from cadaveric tissue, Feinstein et al. (1955) made the estimates set out in Table 1.1.

TABLE 1.1

Number of Muscle Fibres in Various Human Muscles (results given to nearest 50)

Muscle	No. of muscle fibres	Author
First lumbrical	10 250^*	Feinstein et al. (1955)
External rectus	27 000	Feinstein et al. (1955)
Platysma	27 000	Feinstein et al. (1955)
First dorsal interosseous	40 500	Feinstein et al. (1955)
Sartorius	128 150^*	MacCallum (1898)
Brachioradialis	129 200^*	Feinstein et al. (1955)
Tibialis anterior	271 350	Feinstein et al. (1955)
Medial gastrocnemius	1 033 000	Feinstein et al. (1955)

^*Average values

The long gestation period in man allows sufficient time for the precursors of the muscle fibres to have finished dividing and to have formed the adult complement of fibres before birth (MacCallum, 1898). In species with a shorter gestation period the number of fibres continues to increase in the neonatal period. At birth the human fibres are slender, measuring about 10–20 μm in diameter. Throughout childhood, and particularly during the growth spurt in puberty, the sizes increase and eventually attain adult dimensions, with most diameters in the 40–80 μm range (see Figure 1 of Brooke and Engel, 1969). So far as length is concerned, it is assumed that individual fibres run from one end of the muscle to the other; in the human sartorius muscle such fibres may not be functionally continuous; certainly the thigh muscles possess more than one innervation zone and it is possible that long fibres may be composed of two or more shorter fibres arranged end-to-end.

Figure 1.1 (Upper) Structure of the sarcolemma, showing the double layer of lipid molecules and an ‘intrinsic’ protein (see text). (Lower) Membranes, nuclei and organelles seen at the surface of a muscle fibre; the mitochondrion would measure about 1.5 μm in its long diameter

STRUCTURE OF THE MUSCLE FIBRE

Sarcolemma (plasmalemma)

All living cells are bounded by a membrane; that of the muscle fibre is termed the sarcolemma and is some 75

thick. The sarcolemma resembles the membrane of the nerve fibre in possessing the special property of excitability, enabling electrical impulses to be transmitted down the length of the cell (see page 20). In the region of the innervation zone (motor end-plate) the sarcolemma is highly convoluted, due to the presence of junctional folds (page 27). Elsewhere along the surface of the fibre the membrane displays much shallower folds; these result from slackness of the membrane when the fibre is in its resting or contracted states and they disappear if the fibre is passively stretched. There are also numerous very small in-pocketings of membrane, the caveolae, which are connected to the surface membrane by narrow necks; their function is uncertain though they can also act as reserve sources of membrane during stretching of the fibre (Dulhunty and Franzini-Armstrong, 1975). Biochemical and ultrastructural investigations indicate that the sarcolemma is largely composed of lipid molecules arranged perpendicularly to the surface of the fibre and forming two layers (Figure 1.1, upper; see also Capaldi, 1974). The hydrophilic ‘heads’ of the lipid molecules form the internal and external surfaces of the membrane while the hydrophobic ‘tails’ make up the interior of the membrane. The membrane also contains proteins, of which two types are generally recognized; these are referred to as extrinsic and intrinsic. Extrinsic proteins are only attached at the internal or external surfaces of the membrane and can be dislodged relatively easily by chemical means. In contrast, intrinsic proteins penetrate the full thickness of the membrane and are difficult to remove. Among the special proteins known to be localized in the sarcolemma are (a) transport systems for sugars, lipids and, amino acids; (b) kinases for phosphorylating various membrane proteins; (c) adenylate cyclase, responsible for synthesizing cyclic AMP; (d) ATPase enzymes for pumping cations across the membrane (one type for sodium and potassium and another for calcium and magnesium); and (e) carrier molecules (ionophores), each of which can select one species of ion (sodium, potassium or chloride) and transfer it across the membrane (see page 24). In the end-plate region the sarcolemma also contains two special proteins which combine with acetylcholine; these are the acetylcholine receptor and the hydrolytic enzyme, acetylcholinesterase. Since much of the membrane lipid has a melting point below body-temperature the sarcolemma would be expected to have fluid properties. By labelling a spot of membrane with a fluorescent dye and then observing its enlargement under the microscope Fambrough et al. (1974) were able to show that this was indeed the case.

Basement membrane

Just outside the sarcolemma and clearly visible in electronmicrographs is the basement membrane (Figure 1.1, lower). This membrane is about 500

thick and is composed of proteins and polysaccharides. It is probable that the basement membrane provides a special ionic milieu for the muscle fibre by restricting the further diffusion of electrolytes once these have crossed the sarcolemma. In addition the basement membrane helps to maintain the shape of the muscle fibre by providing external support. If the muscle fibre is damaged the membrane may be spared and can then guide the regenerating myoblasts in the formation of a new fibre.

Nuclei

Each muscle fibre contains numerous nuclei (myonuclei) which, in health, are dispersed along the inner surface of the sarcolemma, particularly in the region of the motor end-plate. The nucleus is bounded by two membranes, the outer one of which may join the sarcoplasmic reticulum (Figure 1.1, lower).

Indistinguishable from the myonuclei with the light microscope are the nuclei of the satellite cells. These cells probably account for less than 1 per cent of the muscle fibre nuclei in the adult. They can only be differentiated from the myonuclei by the electronmicroscope, which reveals the presence of twin membranes separating the cytoplasm of the satellite cell from that of the muscle fibre. The satellite cells are of particular importance for the regeneration of muscle following disease or injury (page 100).

Myofibrils

The most obvious structures within the muscle fibre are the myofibrils, which are the units responsible for contraction and relaxation of the fibre (Figure 1.2). Each myofibril is about 1 μm in diameter and, even with the light microscope, can be seen to have a banded, or striated, appearance. The ‘dark’ and ‘light’ striations are termed the A- and I-bands respectively; in the relaxed muscle fibre the centre of the A-band has a light region, the H-zone, which is itself bisected by a ‘dark’ M-line. In the centre of the I-band is a dark Z-line (Z-disc). The striations are caused by the fact that the part of the myofibril in the A-band has a refractive index which is substantially higher than that of the fluid medium, or sarcoplasm, in which the myofibrils are embedded. The pattern of one dark band followed by one light band is repeated every 2.2 μm (measured with the muscle in the relaxed state), the segment between two successive Z-lines being termed a sarcomere. All the myofibrils within a healthy muscle fibre are in register, such that the light and dark bands of one myofibril are adjacent to the cor...

Table of contents

• Cover image
• Title page
• Table of Contents
• Dedication
• Copyright
• INTRODUCTION
• SYMBOLS, UNITS OF MEASUREMENT AND ABBREVIATIONS
• PART 1: MUSCLE FIBRES AND MOTONEURONES
• PART 2: DISORDERS OF MUSCLE AND NERVE
• APPENDICES
• REFERENCES
• INDEX