Review of Medical Physiology - William F. Ganong 2002

Physiology of Nerve and Muscle Cells
Excitable Tissue: Muscle
Skeletal Muscles - Muscle Properties in the Intact Organism

Effects of Denervation

Normally, in intact humans and animals, skeletal Muscles do not contract in the absence of motor nerve stimulation. Impaired innervation leads to Muscle atrophy and causes pathological excitability of the Muscle tissue, as well as an increased sensitivity to circulating acetylcholine (denervation supersensitivity, see Chapter 4). Consequently, weak, uncoordinated contractions of individual muscle fibers (fibrillations) appear. This is a classic sign of a lower motor neuron lesion. If the motor nerve regenerates, the fibrillations cease. Typically, such contractions are invisible to the naked eye; It is important not to confuse them with fasciculations, which are visible twitches of groups of muscle fibers resulting from pathological impulses originating in spinal motor Neurons.

Motor Unit

The axon of a spinal motor neuron branches into several collateral fibers, each supplying a single muscle fiber. Therefore, under normal conditions, the contraction of an individual muscle fiber in vivo is impossible. Stimulation of a single motor neuron results in the contraction of multiple fibers.

The functional combination of a motor neuron and the muscle fibers it innervates is called a motor unit. The number of fibers per motor unit varies and depends on the specific function of the muscle. In the Muscles of the hand and the Eyeball—those responsible for precise, highly coordinated movements—a single motor unit contains three to six muscle fibers. In the gastrocnemius muscle of a cat, there are 120–165 fibers per motor unit, and the large back muscles of humans contain even more.

Each spinal motor neuron innervates fibers of only one type; consequently, all muscle fibers within a motor unit share identical characteristics. Depending on the muscle fiber type (see Table 3-3) and the duration of a single twitch, motor units are classified into fast and slow. Slow motor units contain small-sized neurons with low conduction velocities, whereas fast motor units comprise large neurons with high conduction velocities (the size principle). During most movements involving the large limb muscles, slow (small) units are recruited first; they are fatigue-resistant and utilized most frequently. Fast units, which fatigue easily and rapidly, are typically engaged in movements requiring significant Muscle contraction force.

Differences among various types of motor units are not only genetically determined but also heavily influenced by other factors, particularly the level of their activity (see below). If the nerve supplying a slow muscle is severed and replaced by a nerve that previously innervated a fast muscle, the regenerating transplanted nerve will eventually take over the Innervation of the muscle. Consequently, the muscle gradually acquires fast-twitch characteristics, accompanied by corresponding shifts in muscle protein isoforms and Myosin ATPase activity. Such changes occur following a remodeling of the muscle's activity profile. In experiments involving The stimulation of these muscles, altering solely the electrical stimulation pattern can induce changes in Gene Expression and MHC isoforms.

Electromyography

The activation of motor units can be studied using electromyography (EMG)—the recording of muscle electrical activity, which is graphically displayed on an oscilloscope screen. This Procedure is completely painless and is performed by placing small metal disks on the Skin over the muscle being studied or by inserting subcutaneous needle electrodes. The graphical recording of changes in muscle electrical activity is called an electromyogram (EMG). A typical EMG is shown in Fig. 3-12.

Factors Determining Muscle Activity

Electromyography has revealed that skeletal muscles in healthy individuals exhibit virtually no spontaneous activity at rest. During low-intensity voluntary movements, nerve impulses originate from a small number of motor unit neurons, whereas increasing the load recruits a greater number of motor units. This process is sometimes referred to as motor unit recruitment. Thus, the strength of a muscular response depends on the number of activated motor units. Additionally, the frequency of nerve impulses plays a significant role, as the tension developed during tetanic contraction is much greater than during single twitches. Muscle length is also a determining factor. Finally, nerve impulses in motor units are generated asynchronously, meaning they are phase-shifted relative to one another. Due to this asynchronous neural activity, the responses of individual muscle fibers merge into a smooth, continuous muscle contraction.

Skeletal Muscle Strength

Human skeletal muscles can generate a tension of 3–4 kg per 1 cm² of cross-sectional area. This value is identical to that obtained in numerous animal experiments and appears to be constant across all mammalian species. Because many human muscles possess a relatively large cross-sectional area, they are capable of developing substantial tension.

For example, the gastrocnemius muscle not only Supports the entire body weight during upward locomotion but also withstands loads several times greater when the FOOT strikes the ground during running or jumping. An even more impressive example is the gluteus maximus muscle, which can generate a force of up to 1200 kg. The total force that all the muscles of a healthy human body could develop if they contracted simultaneously is approximately 22 tons.

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Fig. 3-12. Electromyographic recording of biopotentials from the human biceps and triceps muscles during alternating flexion and extension at the elbow joint (after ВС Garoutte).

Role of Muscles in Posture and Movement

All movements occur with maximal utilization of the physiological principles described above. For instance, the attachment points of muscles on the Skeleton are arranged such that most muscles are at resting length at the onset of contraction.

In muscles spanning more than one joint, movement at one joint can compensate for movement at another, so that the overall length of the muscle changes only slightly during contraction. Such nearly isometric contraction allows for The Development of maximal tension. Specifically, the sartorius muscles run from the pelvis across the Hip and knee joints to the Tibia and Fibula. Contraction of this muscle causes hip flexion.

During hip flexion at the hip joint, the lengthening of the portion of the sartorius muscle that crosses the hip joint compensates for the shortening of the portion that crosses the knee joint. During complex movements involving numerous muscles, their mutual coordination is orchestrated to provide optimal contraction conditions for at least some of them. The points of application of muscular force are often positioned relative to joints in a way that forms levers, allowing maximum force to be generated with minimal muscle tension. This is crucial not only for the muscles themselves but also for bones and tendons. Muscle contractions are organized such that the load on bones and the ligamentous-articular apparatus rarely exceeds 50% of their ultimate strength, protecting them from injury.

During walking, each limb rhythmically goes through a stance phase, when the foot is in contact with the ground, and a swing phase, when the foot is in the air. The stance phases of both legs overlap; consequently, There are two periods of double support during each gait cycle.

At the beginning of each step, a brief, sharp increase in tension is observed in the flexor Muscles of the Leg, after which the leg enters a period of minor tension increase. Thus, during each step, the muscles are in an active state for only a short duration, meaning that prolonged walking causes relatively little fatigue.

A healthy young individual walking at a comfortable pace moves at a speed of about 80 m/min, generating a power output of 150–175 W.

In studies conducted with young volunteers asked to walk at their most comfortable pace, it was found that all of them chose a speed of about 80 m/min, at which Energy Expenditure is minimal. Walking at speeds either faster or slower than this optimum requires more energy.

Although walking is a complex reflex-motor act, it proceeds more or less automatically. Animal experiments have revealed that this process is programmed within specifically organized Neural Pathways in the Spinal Cord and activated by precise command signals. This is quite similar to the initiation of activity profiles by command neurons in invertebrates.

Muscle Pathology

As already noted, Mutations in genes encoding various Components of the dystrophin-glycoprotein complex cause muscular dystrophy, a syndrome characterized by progressive muscle weakness. Some of the many forms of this condition can lead to severe disability or death. X-linked Duchenne muscular dystrophy affects approximately 1 in 3,000 newborn boys and typically results in death before the age of 30. This dystrophy is caused by mutations in the dystrophin gene, which lead to a complete absence of dystrophin in the muscles. In a milder form of the disease—Becker muscular dystrophy—dystrophin is present in the muscles, but it is either modified or produced in insufficient quantities. Various Forms of limb-girdle muscular dystrophy are associated with mutations in genes encoding sarcoglycans.

At neuromuscular junctions, dystrophin is replaced by utrophin, a structurally similar protein encoded by a different gene. In genetically modified dystrophin-deficient mice in which utrophin is overexpressed, There is a significant improvement in Muscle Function, proving that utrophin can functionally substitute for dystrophin. Therefore, active research is currently underway to find pharmacological or other means of stimulating the utrophin gene in individuals suffering from Duchenne muscular dystrophy.

Mutations in genes encoding Enzymes involved in the METABOLISM of CARBOHYDRATES, fats, and Proteins, as well as in ATP production within muscle tissue, cause metabolic myopathies. One such condition is McArdle disease, which is described in Chapter 17.

Metabolic myopathies manifest in various ways depending on the specific genetic defect; however, their common hallmark is rapid muscle fatigue and, frequently, The breakdown of muscle tissue resulting from the accumulation of toxic metabolic products.

In various forms of myotonia, the relaxation phase following voluntary muscle contraction is prolonged. Myotonias are caused by abnormalities in genes located on Chromosomes 7, 17, and 19, which lead to structural defects in Na⁺ or Cl^- channels.

Intensive research is currently underway to explore the possibility of implanting normal genes responsible for muscle tissue development in patients with muscular dystrophy, though many challenges in this direction remain unresolved.

Muscle Development

Although discussing the Embryogenesis of muscles is beyond The Scope of this book, It is worth noting that recent years have shed light on many previously unknown mechanisms of the Genetic control of muscle development.

A leading role in this process is played by the protein myogenin, which acts as a Transcription factor for the relevant genes. Under its influence, fibroblasts differentiate into muscle Cells. Mice homozygous for the mutant myogenin gene die shortly after birth due to inadequate development of muscle tissue, including the Respiratory Muscles.