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Peripheral Nerve, Neuromuscular Junction, and Muscle Anatomy 

Peripheral Nerve, Neuromuscular Junction, and Muscle Anatomy
Chapter:
Peripheral Nerve, Neuromuscular Junction, and Muscle Anatomy
Author(s):

Jennifer A. Tracy

DOI:
10.1093/med/9780190214883.003.0006
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Introduction

After exiting the spinal cord, individual nerve roots coalesce to form plexi and peripheral nerves. These nerves innervate muscle and skin. Clinical localization requires a working knowledge of this anatomy. By evaluating the distribution of muscle weakness, sensory loss (Figure 6.1), and reflexes, it is often possible to localize lesions and focus a differential diagnosis.

Figure 6.1 Cutaneous Innervation Map.
A and B, Sensory distribution mapped by peripheral nerve. C, Sensory distribution mapped by dermatome. Total distribution of dermatomes is depicted alternatively in the right and left halves to best illustrate total distribution of innervation of each nerve root.
Figure 6.1 Cutaneous Innervation Map.
A and B, Sensory distribution mapped by peripheral nerve. C, Sensory distribution mapped by dermatome. Total distribution of dermatomes is depicted alternatively in the right and left halves to best illustrate total distribution of innervation of each nerve root.
Figure 6.1 Cutaneous Innervation Map.
A and B, Sensory distribution mapped by peripheral nerve. C, Sensory distribution mapped by dermatome. Total distribution of dermatomes is depicted alternatively in the right and left halves to best illustrate total distribution of innervation of each nerve root.

Figure 6.1
Cutaneous Innervation Map.

A and B, Sensory distribution mapped by peripheral nerve. C, Sensory distribution mapped by dermatome. Total distribution of dermatomes is depicted alternatively in the right and left halves to best illustrate total distribution of innervation of each nerve root.

(Adapted from Kilfoyle DH, Jones LK, Mowzoon N. Disorders of the peripheral nervous system. Part B: Specific inherited and acquired disorders of the peripheral nervous system. In: Mowzoon N, Flemming KD, editors. Neurology board review: an illustrated study guide. Rochester [MN]: Mayo Clinic Scientific Press and Florence [KY]: Informa Healthcare USA; c2007. p. 799–845. Used with permission of Mayo Foundation for Medical Education and Research.)

This chapter reviews the anatomy of the peripheral nerves, neuromuscular junction, and muscle. The autonomic nervous system is discussed in Chapter 19, “Autonomic Nervous System.”

Peripheral Nerve Anatomy

Spinal Nerve Roots

The spinal nerve roots consist of dorsal and ventral roots that extend from the spinal cord. The dorsal root ganglion contains a bipolar neuron that is the sensory nerve cell body. It is extraspinal, located along the dorsal root before the dorsal and ventral roots combine to form the spinal root at each level. There are 8 cervical spinal nerve roots, 12 thoracic, 5 lumbar, 5 sacral, and 1 coccygeal on each side. They exit the spinal canal via intervertebral foramina as spinal nerves. Spinal nerves provide sensory cutaneous innervation, with a cutaneous area innervated by a single spinal nerve referred to as a dermatome. Diagrams are provided as “dermatome maps,” but it is important to remember that there is actually considerable overlap of dermatomal supply (Figure 6.1).

Cervical and Brachial Plexus

Spinal nerves ultimately form various plexi. The C1-C4 motor roots comprise the cervical plexus and provide innervation to the neck muscles, diaphragm, and lower trapezius. The C5-T1 nerve roots continue to form the brachial plexus (Figure 6.2). The upper trunk of the brachial plexus is made up of the C5-C6 nerve roots, the middle trunk is an extension of the C7 nerve root, and the lower trunk consists of the C8-T1 nerve roots. Each trunk then divides into anterior and posterior divisions, with the anterior divisions of the upper and middle trunks forming the lateral cord, the posterior divisions of all 3 trunks becoming the posterior cord, and the anterior division of the lower trunk becoming the medial cord.

Figure 6.2 Anatomical Schema of the Brachial Plexus and Peripheral Nerves of the Upper Extremity.
Note the claw hand deformity of ulnar neuropathy, thenar muscle atrophy of median neuropathy at the wrist, and wristdrop of radial neuropathy.

Figure 6.2 Anatomical Schema of the Brachial Plexus and Peripheral Nerves of the Upper Extremity.

Note the claw hand deformity of ulnar neuropathy, thenar muscle atrophy of median neuropathy at the wrist, and wristdrop of radial neuropathy.

(Adapted from Kilfoyle DH, Jones LK, Mowzoon N. Disorders of the peripheral nervous system. Part A: Anatomy of the peripheral nervous system and classification of disorders by localization. In: Mowzoon N, Flemming KD, editors. Neurology board review: an illustrated study guide. Rochester [MN]: Mayo Clinic Scientific Press and Florence [KY]: Informa Healthcare USA; c2007. p. 777–97. Used with permission of Mayo Foundation for Medical Education and Research.)

Peripheral Nerves of the Upper Extremity

The cords divide into named peripheral nerves (Table 6.1). The main branches of the lateral cord are the musculocutaneous nerve (motor supply to coracobrachialis, biceps brachii, and brachialis; sensory supply via lateral cutaneous nerve of the forearm) and a contribution to the median nerve (motor supply to pronator teres, flexor carpi radialis, palmaris longus, and flexor digitorum superficialis). The main branches of the medial cord are the ulnar nerve (motor supply to flexor carpi ulnaris and flexor digitorum profundus [digits 4, 5], then motor supply to abductor digiti minimi, first dorsal and palmar interosseous muscles, adductor pollicis, flexor pollicis brevis, third and fourth lumbricals, opponens digiti minimi, and flexor digiti minimi; sensory supply through palmar cutaneous, dorsal cutaneous branches, and digital nerves) (Figure 6.3) and a contribution to the median nerve (flexor digitorum superficialis; motor supply to anterior interosseous nerve muscles: flexor digitorum profundus [digits 2, 3], flexor pollicis longus, pronator quadratus; to abductor and flexor pollicis brevis, opponens pollicis, and first and second lumbricals; sensory supply to palmar cutaneous branch and palmar digital nerves), as well as the medial cutaneous nerves of the arm and forearm (Figure 6.4). The main branches of the posterior cord are the axillary nerve (motor innervation to deltoid and teres minor; sensory innervation to upper lateral cutaneous nerve of the arm) (Figure 6.5) and radial nerve (motor innervation to triceps, brachioradialis, extensor carpi radialis longus and brevis, and anconeus, then splitting off into the superficial radial sensory branch and the motor-only posterior interosseous nerve, which innervates multiple muscles, including the supinator, extensor carpi ulnaris, and finger extensor muscles) (Figure 6.5). Other sensory innervation from the radial nerve is via the posterior and lower lateral cutaneous nerves of the arm and the posterior cutaneous nerve of the forearm.

Table 6.1 Muscle Innervation of the Upper Extremity and Trunk

Muscle

Nerve Roots

Trunk

Cord

Nerve

Diaphragm

C3-C5

Phrenic

Rhomboids

C4, C5

Dorsal scapular

Serratus anterior

C5-C7

Long thoracic

Supraspinatus

C5, C6

Upper

Suprascapular

Infraspinatus

C5, C6

Upper

Suprascapular

Deltoid

C5, C6

Upper

Posterior

Axillary

Biceps brachii

C5, C6

Upper

Lateral

Musculocutaneous

Triceps

C6-C8

Upper/middle/lower

Posterior

Radial

Pronator teres

C6, C7

Upper/middle

Lateral

Median

Flexor carpi radialis

C6, C7

Upper/middle

Lateral

Median

Flexor carpi ulnaris

C8, T1

Lower

Medial

Ulnar

Flexor digitorum superficialis

C7, C8, T1

Middle/lower

Lateral/medial

Median

Flexor digitorum profundus

C7, C8, T1

Middle/lower

Lateral/medial

Median (2,3) (anterior interosseous); ulnar (4,5)

Flexor pollicis longus

C7, C8, T1

Middle/lower

Lateral/medial

Median (anterior interosseous)

Extensor digitorum

C7, C8

Middle/lower

Posterior

Radial (posterior interosseous)

Extensor indicis proprius

C7, C8

Middle/lower

Posterior

Radial (posterior interosseous)

Abductor pollicis brevis

C8, T1

Lower

Medial

Median

Abductor digiti minimi

C8, T1

Lower

Medial

Ulnar

First dorsal interosseous

C8, T1

Lower

Medial

Ulnar

Figure 6.3 Ulnar Nerve and the Muscles It Innervates.

Figure 6.3 Ulnar Nerve and the Muscles It Innervates.

(Adapted from Rosse C, Gaddum-Rosse P. Hollinshead’s textbook of anatomy. 5th ed. Philadelphia [PA]: Lippincott-Raven; c1997. Used with permission.)

Figure 6.4 Median Nerve and the Muscles It Innervates.

Figure 6.4 Median Nerve and the Muscles It Innervates.

(Adapted from Rosse C, Gaddum-Rosse P. Hollinshead’s textbook of anatomy. 5th ed. Philadelphia [PA]: Lippincott-Raven; c1997. Used with permission.)

Figure 6.5 Axillary and Radial Nerves and the Muscles They Innervate.

Figure 6.5 Axillary and Radial Nerves and the Muscles They Innervate.

(Adapted from Rosse C, Gaddum-Rosse P. Hollinshead’s textbook of anatomy. 5th ed. Philadelphia [PA]: Lippincott-Raven; c1997. Used with permission.)

Important early branches off nerve roots before the initiation of the brachial plexus include the dorsal scapular nerve, which extends directly from the C5 nerve root and participates in innervation of rhomboid muscles; a branch from C5 which contributes to the phrenic nerve; and the long thoracic nerve (from roots C5-C7), which innervates the serratus anterior. Important branches off the upper trunk include the suprascapular nerve, which innervates the supraspinatus and infraspinatus, and a branch to the subclavius muscle.

Thoracic Level Nerves

Thoracic nerve roots extend out along trunk musculature, providing motor innervation (hence local outpouching of muscle that can be seen in thoracic radiculopathies) and sensory cutaneous innervation (Figure 6.1C).

Lumbar Plexus and Peripheral Nerves of the Lower Extremity

Muscle innervation of the lower extremity is outlined in Table 6.2. The L1-L3 and most of the L4 nerve roots comprise the lumbar plexus (Figure 6.6). Prior to plexus formation, the L1 nerve gives off the iliohypogastric, ilioinguinal, and, with a contribution from L2, the genitofemoral nerve. L2 and L3 give rise to the lateral femoral cutaneous nerve. The L2-L4 roots via the plexus break off into an anterior division, which becomes the femoral nerve (motor innervaton to the iliopsoas, quadriceps, and sartorius and sensory innervation as the intermediate and medial cutaneous nerves of the thigh and the saphenous nerve) (Figure 6.7). A posterior division becomes the obturator nerve (motor supply to obturator externus, gracilis, adductor longus, and adductor brevis muscles [note that the adductor magnus is supplied by both obturator and sciatic nerves]); there is also a cutaneous branch mediating sensation to the medial thigh.

Table 6.2 Muscle Innervation of the Lower Extremity

Muscle

Nerve Roots

Nerve

Iliopsoas

L2-L4

Femoral

Adductor longus

L2-L4

Obturator

Vastus medialis

L2-L4

Femoral

Vastus lateralis

L2-L4

Femoral

Rectus femoris

L2-L4

Femoral

Gluteus medius

L4, L5, S1

Superior gluteal

Gluteus maximus

L5, S1, S2

Inferior gluteal

Tensor fasciae latae

L4, L5, S1

Superior gluteal

Biceps femoris (short head)

L5, S1, S2

Sciatic (peroneal division)

Biceps femoris (long head)

L5, S1, S2

Sciatic (tibial division)

Tibialis anterior

L4, L5

Deep peroneal

Medial gastrocnemius

S1, S2

Tibial

Peroneus longus

L5, S1

Superficial peroneal

Tibialis posterior

L5, S1

Tibial

Peroneus tertius

L5, S1

Deep peroneal

Abductor hallucis

S1, S2

Tibial (medial plantar)

Figure 6.6 Lumbar and Sacral Plexus.

Figure 6.6 Lumbar and Sacral Plexus.

(Modified from Hebl JR, Lennon RL, editors. Mayo Clinic atlas of regional anesthesia and ultrasound-guided nerve blockade. Rochester [MN]: Mayo Clinic Scientific Press and New York [NY]: Oxford University Press; c2010. Used with permission of Mayo Foundation for Medical Education and Research.)

Figure 6.7 Femoral Nerve and the Muscles It Innervates.

Figure 6.7 Femoral Nerve and the Muscles It Innervates.

(Adapted from Rosse C, Gaddum-Rosse P. Hollinshead’s textbook of anatomy. 5th ed. Philadelphia [PA]: Lippincott-Raven; c1997. Used with permission.)

A remaining part of the L4 nerve that does not enter the lumbar plexus joins with the L5 nerve root to form the lumbosacral trunk. The lumbosacral trunk, S1-S3, and part of S4 become the sacral plexus (Figure 6.6). The main branch off this plexus is the sciatic nerve (providing motor supply to hamstring muscles and part of the nerve supply to the adductor magnus), which branches near the popliteal fossa into the common peroneal and tibial nerves (Figure 6.8). The common peroneal nerve divides near the fibula into the deep peroneal and superficial peroneal nerves. The deep peroneal nerve provides motor innervation to the tibialis anterior, the extensor hallucis, the digitorum longus and brevis, and the peroneus tertius and sensory innervation to the sides of and space between the great and second toe. The superficial peroneal nerve provides motor innervation to the peroneus longus and brevis and sensory innervation to the distal anterolateral leg and dorsum of the foot (Figure 6.9). The tibial nerve gives motor innervation to the gastrocnemius, soleus, flexor digitorum longus, posterior tibialis, and flexor hallucis longus. The sural nerve comes off the tibial nerve and gives sensory innervation to the lateral foot. The tibial nerve ultimately divides into the medial and lateral plantar nerves. The medial plantar nerve gives motor supply to the abductor hallucis, flexor hallucis brevis, and flexor digitorum brevis and sensory supply to the medial sole of the foot. The lateral plantar nerve gives motor supply to the abductor digiti minimi, among other muscles of the foot, and provides sensory innervation to the lateral sole of the foot.

Figure 6.8 Peroneal Nerve and the Muscles It Innervates.

Figure 6.8 Peroneal Nerve and the Muscles It Innervates.

(Adapted from Rosse C, Gaddum-Rosse P. Hollinshead’s textbook of anatomy. 5th ed. Philadelphia [PA]: Lippincott-Raven; c1997. Used with permission.)

Figure 6.9 Sciatic and Tibial Nerves and the Muscles They Innervate.

Figure 6.9 Sciatic and Tibial Nerves and the Muscles They Innervate.

(Adapted from Rosse C, Gaddum-Rosse P. Hollinshead’s textbook of anatomy. 5th ed. Philadelphia [PA]: Lippincott-Raven; c1997. Used with permission.)

Other important nerves include the superior gluteal nerve, which is derived primarily from L5 (but also L4 and S1) and supplies the gluteus medius, gluteus minimus, and tensor fasciae latae, and the inferior gluteal nerve, arising from primarily the S1 (but also L5 and S2) nerve roots, supplying the gluteus maximus. These muscles are particularly important in electromyography when the question is whether there are affected L5- or S1-innervated muscles outside of the sciatic nerve distribution.

Clinical Localization

The distribution of muscle weakness in combination with the distribution of sensory loss may allow clinical localization. A common localization question regarding the lower extremity is when a patient presents with footdrop. To distinguish whether the footdrop is related to an L5 radiculopathy versus a peroneal neuropathy, inversion (posterior tibialis) should be assessed. The posterior tibialis is an L5/tibial nerve–innervated muscle. Thus, weakness of this muscle (in addition to the anterior tibialis and peronei) suggests an L5 nerve root lesion.

In the upper extremity, weakness of the triceps, but not the brachioradialis, supinator, extensor indicis, or extensor pollicis brevis, might suggest a radial nerve injury at the spiral groove or above.

Microscopic Peripheral Nerve Anatomy

The main classes of peripheral nerve fibers are large myelinated fibers, which generally subserve motor functions and what are classically termed large fiber sensory modalities (that is, sensation to vibration, touch pressure, and proprioception), and small fibers (myelinated or unmyelinated). Small fiber sensory modalities include temperature perception and pain (including heat pain) perception.

The anatomy of nerve at a pathologic level consists of the endoneurium, perineurium, and epineurium (Figure 6.10). The endoneurium is in the main substance of the nerve, containing large and small nerve fibers. These fibers are grouped into structures called fascicles, each of which is surrounded by connective tissue referred to as the perineurium. Multiple fascicles are surrounded by the epineurium. Nerve biopsy is sometimes used as a diagnostic tool in peripheral nerve dysfunction; in most cases, biopsy is performed on a distal cutaneous sensory nerve, but in other cases of focal abnormalities, more proximal fascicular nerve biopsies have been undertaken. Nerve biopsy allows assessment of abnormalities in the fibers themselves, including in fiber density, and assessment of interstitial changes such as inflammation, edema, amyloid deposition, or vasculitis.

Figure 6.10 Histologic Features of a Peripheral Nerve.
A nerve is subdivided into fascicles by the perineurium, with multiple motor and sensory nerve fibers intermingled in each fascicle.

Figure 6.10 Histologic Features of a Peripheral Nerve.

A nerve is subdivided into fascicles by the perineurium, with multiple motor and sensory nerve fibers intermingled in each fascicle.

(Adapted from Benarroch EE, Daube JR, Flemming KD, Westmoreland BF. Mayo Clinic medical neurosciences: organized by neurologic systems and levels. 5th ed. Rochester [MN]: Mayo Clinic Scientific Press and Florence [KY]: Informa Healthcare USA; c2008. Chapter 13, The peripheral level; p. 491–546. Used with permission of Mayo Foundation for Medical Education and Research.)

The inner portion of the nerve is relatively negatively charged compared to the extracellular space (approximately −70 mV); internal to the nerve are high concentrations of potassium and negatively charged proteins and other anions; the extracellular space contains high concentrations of sodium and chloride. With an action potential, sodium channels open, allowing sodium entry into the nerve, and depolarization spreads down the nerve.

In the peripheral nervous system, Schwann cells produce myelin, which is an insulating substance surrounding the axon. This allows more efficient spread of an action potential along the axon between nodes of Ranvier by a process called saltatory conduction. The term internodes refers to the span of myelinated axon between the nodes. Unmyelinated fibers have a slower spread of action potentials because of the lack of myelin. Repolarization occurs through sodium channel inactivation and passage of potassium ions. A sodium-potassium adenosine triphosphatase is important to establish the resting membrane potential.

Many pathologic processes can affect the peripheral nerve, resulting in dysfunction (Figure 6.11). Clinical peripheral nerve disorders are discussed in Volume 2, Section VII, Chapter 40, “Peripheral Nerve Disorders.”

  • There are 8 cervical spinal nerve roots, 12 thoracic, 5 lumbar, 5 sacral, and 1 coccygeal on each side.

  • The C5-T1 nerve roots form the brachial plexus.

  • The main branches of the lateral cord are the musculocutaneous and median nerves. The main branches of the medial cord are the ulnar and median nerves. The main branches of the posterior cord are the axillary and radial nerves.

  • The dorsal scapular nerve extends directly from the C5 nerve root and participates in innervation of rhomboid muscles.

  • The L1-L3 and most of the L4 nerve roots comprise the lumbar plexus.

  • The L2-L4 roots via the plexus break off into an anterior division, which becomes the femoral nerve.

  • The main branch of the sacral plexus is the peroneal and tibial nerves.

Figure 6.11 Diagram of Pathologic Changes in Peripheral Nerve Fibers.
A, Normal axon. B, Wallerian degeneration occurs distal to local destruction of an axon and is associated with central chromatolysis of the cell body and muscle fiber atrophy. Regeneration occurs along the connective tissue path. C, Axonal dystrophy results in distal narrowing and dying back of nerve terminals due to either intrinsic axon or motor neuron disease. D, Segmental demyelination destroys myelin at scattered internodes along the axon without causing axonal damage.

Figure 6.11 Diagram of Pathologic Changes in Peripheral Nerve Fibers.

A, Normal axon. B, Wallerian degeneration occurs distal to local destruction of an axon and is associated with central chromatolysis of the cell body and muscle fiber atrophy. Regeneration occurs along the connective tissue path. C, Axonal dystrophy results in distal narrowing and dying back of nerve terminals due to either intrinsic axon or motor neuron disease. D, Segmental demyelination destroys myelin at scattered internodes along the axon without causing axonal damage.

(Adapted from Benarroch EE, Daube JR, Flemming KD, Westmoreland BF. Mayo Clinic medical neurosciences: organized by neurologic systems and levels. 5th ed. Rochester [MN]: Mayo Clinic Scientific Press and Florence [KY]: Informa Healthcare USA; c2008. Chapter 13, The peripheral level; p. 491–546. Used with permission of Mayo Foundation for Medical Education and Research.)

Neuromuscular Junction and Muscle Anatomy

Neuromuscular Junction

The neuromuscular junction consists of the presynaptic membrane of a motor neuron, the synaptic cleft, and the postsynaptic muscle membrane. Acetylcholine is stored in vesicles in the presynaptic nerve terminal. When an action potential is generated within the motor neuron, a wave of depolarization travels down the axon and triggers calcium influx at the nerve terminal, with subsequent fusion of the vesicle with the presynaptic membrane and acetylcholine release into the synaptic cleft (Figure 6.12).

Figure 6.12 Functional Anatomy of the Neuromuscular Junction.

Figure 6.12 Functional Anatomy of the Neuromuscular Junction.

(Adapted from Boon AJ. Assessing the neuromuscular junction with repetitive stimulation studies. In: Daube JR, Rubin DI, editors. Clinical neurophysiology. 3rd ed. Oxford [UK]: Oxford University Press; c2009. p. 369–84. Used with permission of Mayo Foundation for Medical Education and Research.)

In normal muscles, the postsynaptic membrane has numerous junctional folds; nicotinic acetylcholine receptors are located in the crests of these folds, and voltage-gated sodium channels are clusters at the bottoms of the folds. The acetylcholine receptors consist of multiple subunits (two α‎, one β‎, one δ‎, and one ε‎ in adults). Two acetylcholine molecules bind to each receptor, triggering what is mainly sodium influx through the receptor, leading to production of an end-plate potential. If depolarization exceeds the threshold for an action potential, the sodium channels also open, leading to muscle fiber depolarization and muscle contraction. Acetylcholine is ultimately cleaved by acetylcholinesterase in the neuromuscular junction.

Skeletal Muscle

Skeletal muscle fibers achieve contraction through components called sarcomeres (Figure 6.13). Sarcomeres are separated from each other by Z disks, which bind thin filaments composed of actin complexed with troponin and tropomyosin. Progressing from the Z disk to the middle of the sarcomere is the A band, which is made up primarily of myosin. At the center of the A band is the H zone, which is devoid of actin, and at the center of the H zone is the M line.

Figure 6.13 Structure of a Sarcomere.
A, Ultrastructure of a muscle fiber. Each fiber is made up of many myofibrils containing filaments of actin and myosin organized in bands A, I, and Z. B, Organization of protein filaments in a myofibril. a, Longitudinal section through 1 sarcomere (Z disk to Z disk) showing overlap of actin and myosin. b, Cross section through A band, where the thin actin filaments interdigitate with the thick myosin filaments in a hexagonal formation. c, Location of specific proteins in a sarcomere. C, Structure of a single muscle fiber cut longitudinally and in cross section. Individual myofibrils are surrounded and separated by sarcoplasmic reticulum. T tubules are continuous with extracellular fluid and interdigitate with the sarcoplasmic reticulum.
Figure 6.13 Structure of a Sarcomere.
A, Ultrastructure of a muscle fiber. Each fiber is made up of many myofibrils containing filaments of actin and myosin organized in bands A, I, and Z. B, Organization of protein filaments in a myofibril. a, Longitudinal section through 1 sarcomere (Z disk to Z disk) showing overlap of actin and myosin. b, Cross section through A band, where the thin actin filaments interdigitate with the thick myosin filaments in a hexagonal formation. c, Location of specific proteins in a sarcomere. C, Structure of a single muscle fiber cut longitudinally and in cross section. Individual myofibrils are surrounded and separated by sarcoplasmic reticulum. T tubules are continuous with extracellular fluid and interdigitate with the sarcoplasmic reticulum.
Figure 6.13 Structure of a Sarcomere.
A, Ultrastructure of a muscle fiber. Each fiber is made up of many myofibrils containing filaments of actin and myosin organized in bands A, I, and Z. B, Organization of protein filaments in a myofibril. a, Longitudinal section through 1 sarcomere (Z disk to Z disk) showing overlap of actin and myosin. b, Cross section through A band, where the thin actin filaments interdigitate with the thick myosin filaments in a hexagonal formation. c, Location of specific proteins in a sarcomere. C, Structure of a single muscle fiber cut longitudinally and in cross section. Individual myofibrils are surrounded and separated by sarcoplasmic reticulum. T tubules are continuous with extracellular fluid and interdigitate with the sarcoplasmic reticulum.

Figure 6.13
Structure of a Sarcomere.

A, Ultrastructure of a muscle fiber. Each fiber is made up of many myofibrils containing filaments of actin and myosin organized in bands A, I, and Z. B, Organization of protein filaments in a myofibril. a, Longitudinal section through 1 sarcomere (Z disk to Z disk) showing overlap of actin and myosin. b, Cross section through A band, where the thin actin filaments interdigitate with the thick myosin filaments in a hexagonal formation. c, Location of specific proteins in a sarcomere. C, Structure of a single muscle fiber cut longitudinally and in cross section. Individual myofibrils are surrounded and separated by sarcoplasmic reticulum. T tubules are continuous with extracellular fluid and interdigitate with the sarcoplasmic reticulum.

(Adapted from Benarroch EE, Daube JR, Flemming KD, Westmoreland BF. Mayo Clinic medical neurosciences: organized by neurologic systems and levels. 5th ed. Rochester [MN]: Mayo Clinic Scientific Press and Florence [KY]: Informa Healthcare USA; c2008. Chapter 13, The peripheral level; p. 491–546. Used with permission of Mayo Foundation for Medical Education and Research.)

When an action potential is initiated, depolarization spreads along the muscle membrane. This continues down the T tubules (which are continuous with the muscle membrane), causing release of calcium into the sarcoplasm from the sarcoplasmic reticulum. This calcium binds to troponin, which exposes myosin-binding sites on actin. Myosin then binds actin (the cross-bridge), adenosine triphosphate bound to myosin is hydrolyzed, and adenosine diphosphate and inorganic phosphate are released from myosin, causing the myosin head to flex, leading to a “power stroke.” Adenosine triphosphate binds to myosin again and the cross-bridge breaks, leaving myosin to bind to the next site on actin. This repeated process causes muscle contraction as sarcomeres shorten.

Normal adult muscle, when viewed in cross section, consists of fibers approximately 30 to 80 µm in diameter with multiple peripherally located nuclei. Muscle fibers are bound by the sarcolemma, external to which is the basal lamina. The endomysium is the connective tissue between muscle fibers. The muscle itself is divided into fascicles, or groups of muscle fibers, surrounded by connective tissue referred to as the perimysium. Epimysium surrounds the muscle as a whole.

Normal muscle consists of type 1 and type 2 fibers, intermixed randomly. Type 1 fibers depend primarily on oxidative metabolism and are considered slow-twitch fibers. Type 2 fibers are considered fast-twitch fibers; type 2A fibers function well in both anaerobic and aerobic states, whereas type 2B fibers function most efficiently in an anaerobic state. Type 1 and 2 fibers can be easily differentiated by adenosine triphosphatase reactivity after incubation at acid or alkaline pH. Mitochondrial enzymes, glycogen and lipid content, myofibrillar integrity, the presence or absence of angulated fibers, vacuoles, inclusions, and some enzyme deficiencies can be readily detected under light microscopy with proper staining.

Multiple proteins contribute to the structural integrity and proper function of the muscle fiber (Figure 6.14). Dystrophin is located on the cytoplasmic side of the muscle membrane and is important for stabilization of the membrane during contraction. The sarcoglycans (α‎, β‎, γ‎, and δ‎) are transmembrane proteins also important for stabilizing the sarcolemma. Emerin is part of the nuclear membrane, and lamin A/C is in the lamina beneath the nuclear membrane. β‎-Dystroglycan is located in the sarcolemmal membrane; it binds to dystrophin and also to extracellular α‎-dystroglycan, which in turn binds to laminin α‎2. Caveolin is associated with calveoli in the sarcolemmal membrane. Calpain is a protease. Dysferlin serves a membrane repair function. Myotilin is associated with the Z disk. These are but a few of the important components of normal muscle structure. Dysfunction in many of the proteins described can result in muscular dystrophies or other myopathies. There are myriad other causes of congenital and acquired myopathies, as well as mitochondrial and metabolic myopathies (see Volume 2, Chapter 42, “Acquired Muscle Disorders,” and Chapter 43, “Inherited Muscle Disorders”).

  • The neuromuscular junction consists of the presynaptic membrane of a motor neuron, the synaptic cleft, and the postsynaptic muscle membrane.

  • On the postsynaptic membrane, nicotinic acetylcholine receptors are located in the crests of junctional folds, and voltage-gated sodium channels are clusters at the bottoms of these folds.

  • Type 1 muscle fibers depend primarily on oxidative metabolism and are considered slow-twitch fibers.

  • Type 2 muscle fibers are considered fast-twitch fibers.

  • Dystrophin is located on the cytoplasmic side of the muscle membrane and is important for stabilization of the membrane during contraction.

Figure 6.14 Dystrophin-Associated Muscle Membrane Protein Complex.
MDPK indicates myotonic dystrophy protein kinase.

Figure 6.14 Dystrophin-Associated Muscle Membrane Protein Complex.

MDPK indicates myotonic dystrophy protein kinase.

(Adapted from Banwell BL. Muscular dystrophies. In: Noseworthy JH, editor. Neurological therapeutics: principles and practice. Vol 2. London [UK]: Martin Dunitz; c2003. p. 2312–27. Used with permission of Mayo Foundation for Medical Education and Research.)