Exercise Physiology and Sports Science

The motor unit is the functional element of muscle contraction

The motor unit (see pp. 228–229 ) is the functional unit of skeletal muscle and consists of a single motor neuron and all the muscle fibers that it activates. A typical skeletal muscle such as the biceps brachii receives innervation from ~750 somatic motor neurons.

When the motor neuron generates an action potential, all fibers in the motor unit fire simultaneously. Thus, the fineness of control for movement varies with the innervation ratio (see pp. 228–229 )—the number of muscle fibers per motor neuron. N60-1 The small motor units that are recruited during sustained activity contain a high proportion of type I muscle fibers (see p. 249 ), which are highly oxidative and resistant to fatigue. The type IIa motor units (see p. 249 ) have larger innervation ratios, contract faster, and have less oxidative capacity and fatigue resistance than type I units. Still larger motor units—recruited for brief periods for rapid, powerful activity—typically consist of type IIx muscle fibers; these have less oxidative capacity (i.e., are more glycolytic) and are much more susceptible to fatigue than type IIa muscle. In practice, it may be best to view muscle fiber types and motor units as a continuum rather than distinct entities.

Within a whole muscle, muscle fibers of each motor unit intermingle with those of other motor units so extensively that a volume of muscle containing 100 muscle fibers is innervated by terminals from perhaps 50 different motor neurons. However, each muscle fiber is innervated by only one motor neuron. Within some muscles, the fibers of a motor unit are constrained to discrete compartments. This anatomical organization enables different regions of a muscle to exert force in somewhat different directions, which enables more precise control of movement.

Muscle force rises with the recruitment of motor units and an increase in their firing frequency

During contraction, the force exerted by a muscle depends on (1) how many motor units are recruited, and (2) how frequently each of the active motor neurons fires action potentials. Motor units are recruited in a progressive order, from the smallest (i.e., fewest number of muscle fibers) and therefore the weakest motor units to the largest and strongest. This intrinsic behavior of motor-unit recruitment is known as the size principle and reflects inherent differences in the biophysical properties of respective motor neurons. For a given amount of excitatory input (i.e., depolarizing synaptic current; I _syn in Fig. 60-1 ), a neuronal cell body with smaller volume and surface area has a higher membrane input resistance. Therefore, the depolarizing voltage rises to threshold more quickly in a neuron with a smaller neuronal cell body than in a neuron with a larger cell body (see Fig. 60-1 ). Because the neurons with the small cell bodies tend to innervate a small number of slow-twitch (type I) muscle fibers, the motor units with the greatest resistance to fatigue are the first to be recruited. Conversely, the neurons with the larger cell bodies tend to innervate a larger number of fast-twitch (type II) fibers, so the largest and most fatigable motor units (type IIx) are the last to be recruited (e.g., during peak levels of force production). Because the relative timing of action potentials in different motor units is asynchronous, the force developed by individual motor units integrates into a smooth contraction. As a muscle relaxes, the firing of respective motor units diminishes in reverse order.

At levels of force production lower than the upper limit of recruitment, gradations in force are accomplished via concurrent changes in the number of active motor units and the firing rate of those that have been recruited— rate coding. Once all the motor units in a muscle have been recruited, any further increase in force results from an increase in firing rate. The relative contribution of motor-unit recruitment and rate coding varies among muscles. In some cases, recruitment is maximal by the time muscle force reaches ~50% of maximum, whereas in others, recruitment continues until the muscle reaches nearly 90% of maximal force.

Not only do the intrinsic membrane properties of motor neurons (i.e., the size principle) affect motor neuron firing, but other neurons that originate in the brainstem project to the motor neurons and release the neuromodulatory neurotransmitters serotonin and norepinephrine (see Fig. 13-7 A and B ). For example, this neuromodulatory input, acting on the motor neurons of small, slow-twitch motor units, can promote self-sustained levels of firing of the motor neurons during the maintenance of posture. In contrast, the withdrawal of this excitatory neuromodulatory input during sleep promotes muscle relaxation. Thus, the brainstem can control the overall gain of a pool of motor neurons.

Compared with type I motor units, type II units are faster and stronger but more fatigable

Within a given motor unit, each muscle fiber is of the same muscle fiber type. As summarized in Tables 9-1 and 9-2 , the three human muscle fiber types—type I, type IIa, and type IIx—differ in contractile and regulatory proteins, the content of myoglobin (and thus color) and of mitochondria and glycogen, and the metabolic pathways used to generate ATP (i.e., oxidative versus glycolytic metabolism). Physical training can modify these biochemical properties, which determine a range of functional parameters, including (1) speeds of contraction and relaxation, (2) maximal force, and (3) susceptibility to fatigue ( Fig. 60-2 ).

In response to an action potential evoked through the motor axon, slow-twitch (type I) motor units (see Fig. 60-2 A , top) require relatively long times to develop moder­ate levels of force and return to rest. In contrast, fast-twitch (types IIa and IIx) motor units exhibit relatively short contraction and relaxation times and develop higher levels of force (see Fig. 60-2 B and C , top). Accordingly, during repetitive stimulation (middle row of Fig. 60-2 ), slow-twitch motor units summate to a fused tetanus at lower stimulation frequencies than do fast-twitch motor units. Indeed, the α motor neurons in the spinal cord that drive slow motor units fire at frequencies of 10 to 50 Hz, whereas those that drive fast motor units fire at 30 Hz to >100 Hz.

The maximal force that can develop per cross-sectional area of muscle tissue is constant across fiber types (~25 N/cm ² ). Therefore, the ability of different motor units to develop active force is directly proportional to the number and diameter of fibers each motor unit contains. In accord with the innervation ratios of motor units, peak force production (middle row of Fig. 60-2 ) increases from type I motor units (used for fine control of movement) to type II motor units (recruited during more intense activities).

The susceptibility to fatigue of a motor unit depends on the metabolic profile of its muscle fibers. The red type I muscle fibers have a greater mitochondrial density and can rely largely on the aerobic metabolism of carbohydrate and lipid as fuel because they are well supplied with capillaries for delivery of O ₂ and nutrients. Type I motor units, although smaller in size (and innervation ratio), are recruited during sustained activity of moderate intensity and are highly resistant to fatigue (see Fig. 60-2 A , bottom). In contrast, the larger type II motor units are recruited less often—during brief periods of intense activity—and rely to a greater extent on short-term energy stores (e.g., glycogen stored within the muscle fiber). Among type II motor units, type IIa motor units have intermediate innervation ratios, a greater mitochondrial density, a larger capacity for aerobic energy metabolism, a greater O ₂ supply, and a higher endurance capacity, and hence are classified as fast fatigue-resistant (bottom of Fig. 60-2 B ). In contrast, type IIx motor units have the highest innervation ratios and a greater capacity for rapid energy production through nonoxidative (i.e., anaerobic) glycolysis, and thus can produce rapid and powerful contractions. However, type IIx units tire more rapidly and are therefore classified as fast fatigable (see Fig. 60-2 C , bottom).

As external forces stretch muscle, series elastic elements contribute a larger fraction of total tension

As sarcomeres contract, some of their force acts laterally—through membrane-associated and transmembrane proteins—on the extracellular matrix and connective tissue that surrounds each muscle fiber. Ultimately, the force is transmitted to bone, typically (but not always) through a tendinous insertion. The structural elements that transmit force from the cross-bridges to the skeleton comprise the series elastic elements of the muscle and behave as a spring with a characteristic stiffness. Stretching resting muscle causes passive tension to increase exponentially with length (see Fig. 9-9 C ). Thus, muscle stiffness increases with length. During an isometric contraction (see pp. 237–238 ), when the external length of a muscle (or muscle fiber) is held constant, the sarcomeres shorten at the expense of stretching the series elastic elements. An isometric contraction can occur at modest levels of force development, such as holding a cup of coffee, as well as during maximal force development, such as when opposing wrestlers push and pull against each other, with neither gaining ground. Physical activity typically involves contractions in which muscles are shortening and lengthening, as well as periods during which muscle fibers are contracting isometrically.

During cyclic activity such as running, muscles undergo a stretch-shorten cycle that may increase total tension while decreasing active tension. For example, as the calf muscles relax as the foot lands and decelerates, the series elastic elements of the calf muscles (e.g., the Achilles tendon, connective tissue within muscles) are stretched and develop increased passive tension (see Fig. 9-9 C ). Thus, when the calf muscles contract to begin the next cycle, they start from a higher passive tension and therefore use a smaller increment in active tension to reach a higher total tension. N60-2 This increased force helps to propel the runner forward.

In a concentric contraction (e.g., climbing stairs), the force developed by the cross-bridges exceeds the external load, and the sarcomeres shorten. During a concentric contraction, a muscle performs positive work (force × distance) and produces power (work/time; see p. 240 ). As shown in Figure 9-9 E , the muscle achieves peak power at relatively moderate loads (30% to 40% of isometric tension) and velocities (30% to 40% of maximum shortening velocity). The capacity of a muscle to perform positive work determines physical performance. For example, a stronger muscle can shorten more rapidly against a given load, and a muscle that is metabolically adapted to a particular activity can sustain performance for a longer period of time before succumbing to fatigue.

In an eccentric contraction (e.g., descending stairs), the force developed by the cross-bridges is less than the imposed load, and the sarcomeres lengthen. During an eccentric contraction, the muscle performs negative work, thereby providing a brake to decelerate the applied force being applied, and absorbs power. Eccentric contractions can occur with light loads, such as lowering a cup of coffee to the table, as well as with much heavier loads, such as decelerating after jumping off a bench onto the floor. At the same absolute level of total force production, eccentric contractions—with increasingly stretched sarcomeres—develop less active tension than do concentric or isometric contractions. Conversely, the passive tension developed by the series elastic elements makes a greater contribution to total tension. As a result, the maximum tension generated eccentrically can be greater than that generated isometrically. When the external force stretches the muscle sufficiently, all the tension is passive and the limit is the breaking point (see Fig. 19-9 B ) of the series elastic elements. Thus, eccentric contractions are much more likely than isometric or isotonic contractions to damage muscle fibers and connective tissue, as occurs with the common injury of a ruptured Achilles tendon.

The action of a muscle depends on the axis of its fibers and its origin and insertion on the skeleton

In addition to the contractile and metabolic properties of muscle fibers discussed above, two anatomical features determine the characteristics of the force produced by a muscle.

The first anatomical determinant of muscle function is the arrangement of fibers with respect to the axis of force production (i.e., the angle of pennation). With other determinants of performance (e.g., fiber type and muscle mass) being equal, muscles that have a relatively small number of long fibers oriented parallel to the axis of shortening (e.g., the sartorius muscle of the thigh; Fig. 60-3 A , top) shorten more rapidly. Indeed, the more sarcomeres are arranged in series, the more rapidly the two ends of the muscle will approach each other. In contrast, muscles that have many short fibers at an angle to the axis (e.g., the gastrocnemius muscle of the calf; Fig. 60-3 A , bottom) develop more force. Indeed, the greater the number of fibers (and sarcomeres) in parallel with each other, the greater the total cross-sectional area for developing force.

The second anatomical determinant of limb movement consists of the locations of the origin and insertion of the muscle to the skeleton. Consider, for example, the action of the brachialis muscle on the elbow joint. The distance between the insertion of the muscle on the ulna and the joint's center of rotation is D, which may be 5 cm. The torque that the muscle produces on the joint is the component of total muscle force that is perpendicular to the ulna, multiplied by D (see Fig. 60-3 B ). An equivalent definition is that torque is the product of the total muscle force multiplied by the moment arm, which is the length of the line segment that runs perpendicular to the muscle and through the center of rotation (see Fig. 60-3 B ). As we flex the elbow, the moment arm is constantly changing and muscle force changes as well. For this joint, we achieve maximum torque at 60 degrees of flexion.

Fluid and energetically efficient movements require learning

To perform a desired movement—whether playing the piano or serving a tennis ball—the nervous system must activate a combination of muscles with the appropriate contractile properties, recruit motor units in defined patterns, and thereby create suitable mechanical interactions among body segments. When we perform movements with uncertainty—as in learning a new skill—actions tend to be stiff because of concurrent recruitment of motor units in antagonistic muscles that produce force in opposite directions. Such superfluous muscle fiber activity also increases the energy requirements for the activity. Even in someone who is skilled, the fatigue of small motor units leads to the recruitment of larger motor units in the attempt to maintain activity, but with loss of fine control and greater energy expenditure. With learning, recruitment patterns become refined and coordinated, and muscle fibers adapt to the task. Thus, movements become fluid and more energetically efficient, as exemplified by the movements of highly trained musicians and athletes, who can make difficult maneuvers appear almost effortless.

Strength versus endurance training differentially alters the properties of motor units N60-3

The firing pattern of the α motor neuron—over time—ultimately determines the contractile and metabolic properties of the muscle fibers in the corresponding motor unit. This principle was demonstrated by cross-innervation experiments in which investigators cut the motor nerve to a muscle composed primarily of fast motor units and switched it with the motor nerve of a muscle composed primarily of slow motor units. N60-4 As the axons regenerate and the muscles recover contractile function over several weeks, the fast muscle becomes progressively slower and more fatigue resistant whereas the slow muscle becomes faster and more susceptible to fatigue. Varying the pattern of efferent nerve impulses via long-term stimulation of implanted electrodes elicits similar changes in muscle properties. A corollary of this principle is that physical activity leads to adaptation only in those motor units that are actually recruited during the activity.

The effects of physical activity on motor-unit physiology depend on the intensity and duration of the exercise. In general, sustained periods of activity of low to moderate intensity performed several times per week— endurance (aerobic) training —result in a greater oxidative capacity of muscle fibers and are manifested by increases in O ₂ delivery, capillary supply, and mitochondrial content (see pp. 1219–1222 ). These adaptations reduce the susceptibility of the affected muscle fibers to fatigue (see pp. 1212–1213 ). The lean and slender build of long-distance (i.e., endurance) runners reflects the abundance of highly oxidative type I and IIa muscle fibers of relatively small diameter, promoting O ₂ and CO ₂ diffusion between capillaries and mitochondria for high levels of aerobic energy production. Further, the high ratio of surface area to volume of the slender body also facilitates cooling of the body during prolonged activity and in hot environments.

In contrast, brief sets of high-intensity contractions performed several times per week— strength (anaerobic) training —result in type IIx motor units that can produce more force and can shorten against a given load at greater velocity by increasing the amount of contractile protein. The hypertrophied muscles of sprinters and weightlifters exemplify this type of adaptation, which relies more on rapid, anaerobic sources of energy production (see p. 1209 ).

ATP and PCr provide immediate but limited energy

At the onset of exercise, or during the transition to a higher intensity of contractile activity, the immediate energy sources are ATP and PCr. As for any other cell, muscle cells break down ATP to ADP and inorganic phosphate (P _i ), releasing ~11.5 kcal/mole of free energy (ΔG) under physiological conditions (see p. 1174 ):

Muscle cells rapidly regenerate ATP from PCr in a reaction that is catalyzed by creatine kinase:

Resting skeletal muscle cells contain 5 to 6 mmol/kg of ATP but 25 to 30 mmol/kg of PCr—representing nearly 5-fold more energy. These two energy stores are sufficient to support intense contractile activity for only a few seconds. When rates of ATP breakdown (see Equation 60-1 ) are high, ADP levels (normally very low) increase and can actually interfere with muscle contraction. Under such conditions, adenylate kinase (also known as myokinase ) transfers the second phosphate group from one ADP to another, thereby regenerating ATP:

The foregoing reaction is limited by the initial pool of ADP, which is small. In contrast, creatine kinase (see Equation 60-2 ) so effectively buffers ATP that [ATP] _i changes very little. Although changes in [ATP] _i cannot provide an effective signal to stimulate metabolic pathways of energy production, the products of ATP hydrolysis—P _i , ADP, and AMP—are powerful signals.

The high-energy phosphates ATP + PCr are historically referred to as phosphagens and are recognized as the immediate energy supply because they are readily available, albeit for only several seconds (see Fig. 60-4 , red curve). This role is of particular importance at the onset of exercise and during transitions to more intense activity, before other metabolic pathways have time to respond.

Anaerobic glycolysis provides a rapid but self-limited source of ATP

When high-intensity exercise continues for more than several seconds, the breakdown of ATP and PCr is followed almost instantly by the accelerated breakdown of intramuscular glycogen to glucose and then to lactate. This anaerobic metabolism of glucose has the major advantage of providing energy quickly to meet the increased metabolic demands of an intense workload, even before O ₂ , glucose, or fatty-acid delivery from blood increases. However, because of the low ATP yield of this pathway, muscle rapidly depletes its glycogen stores, which so that intense activity is limited to durations of ~1 minute (see Fig. 60-4 , purple curve).

Muscle fibers store 300 to 400 g of carbohydrate in the form of glycogen (see p. 1171 ) and, particularly in the case of type II fibers, are rich in the enzymes required for glycogenolysis and glycolysis. In glycogenolysis (see p. 1182 ), phosphorylase breaks down glycogen to glucose-1-phosphate. Activation of the sympathetic nervous system during exercise elevates levels of epinephrine and—by activating β-adrenergic receptors on muscle fibers—promotes the break­down of muscle glycogen. Subsequently, phosphoglucomutase converts glucose-1-phosphate to glucose-6-phosphate (G6P). Muscle fibers can also take up blood-borne glucose using GLUT4 transporters (see p. 1047 ) and use hexokinase to phosphorylate it to G6P. During nonoxidative generation of ATP (see Fig. 60-4 , purple curve), intracellular glycogen is more important than blood-borne glucose in rapidly contributing G6P for entry into glycolysis —breakdown of glucose to pyruvate (see Fig. 58-6 A ).

In the absence of O ₂ , or when glycolysis generates pyruvate more rapidly than the mitochondria can oxidize it (see below), muscle cells can divert pyruvate to lactic acid, which readily dissociates into H ⁺ and lactate. The overall process generates two ATP molecules per glucose molecule:

This anaerobic regeneration of ATP from ADP through breakdown of intramuscular glycogen, although faster than oxidative metabolism, captures only a fraction of the energy stored in glucose. Moreover, the process is self-limiting because the H ⁺ generated from the dissociation of lactic acid can lower pH _i from 7.1 to nearly 6.2; the lower pH inhibits glycolysis and impairs the contractile process, which contributes to muscle fatigue (see p. 1213 ).

Oxidation of glucose, lactate, and fatty acids provides a slower but long-term source of ATP

The body stores only a small amount of O ₂ in the blood, and the cardiovascular and respiratory systems require 1 to 2 minutes to increase O ₂ delivery to muscle to support oxidative metabolism. Endurance training accelerates these adjustments. Nevertheless, before the increase in O ₂ delivery is complete, skeletal muscle must rely on the immediate release of energy from ATP and PCr, as well as anaerobic glycolysis, as just discussed. As blood flow and O ₂ delivery increase over the first 1 to 2 minutes, the contribution of aerobic ATP production reduces the dependence on short-term sources of ATP. Thus, in order to sustain light and intermediate physical activity for longer than ~1 minute, muscle regenerates ATP through oxidative metabolism in the mitochondria of type I and type IIa muscle fibers (see Fig. 60-4 , blue curve). Muscle also uses oxidative metabolism to recover from intense activities of short duration that relied on the immediate and nonoxidative systems of energy supply.

The nonoxidative metabolism of glucose provides nearly 100-fold more energy than is available via the immediate breakdown of ATP and PCr. However, oxidative metabolism of the same amount of glucose provides 15-fold more energy than the nonoxidative metabolism of glucose.

Oxidation of Nonmuscle Glucose

The aerobic metabolism of glucose, although slower than anaerobic glycolysis (see Equation 60-4 ), provides nearly 15-fold more ATP molecules per glucose molecule (see Table 58-4 ): N58-15

The majority of glucose that contracting skeletal muscle oxidizes during aerobic energy production comes from circulating glucose, which in turn originates primarily from the breakdown of the hepatic glycogen stores of 75 to 100 g (see p. 1171 ). Exercising muscle can increase its uptake of circulating glucose by 7- to 40-fold; this uptake is balanced by enhanced hepatic glucose release, so that blood [glucose] is stabilized. An increase in portal vein levels of glucagon, in particular (see Fig. 51-12 ), and a decrease in insulin —together with an increase in epinephrine (see Fig. 58-9 B )—are the main signals for this elevated hepatic glucose output during exercise.

Contracting skeletal muscle is an important sink for blood-borne glucose ( Fig. 60-5 ). Moreover, contractile activity triggers the translocation of additional GLUT4 transporters (see p. 114 ) from the cytosol to the plasma membrane. This process, which is insulin independent and is likely mediated by activation of AMP kinase, supports increased glucose uptake. Because exercise-induced translocation of GLUT4 does not depend on insulin, endurance exercise is an important adjunct in controlling elevated levels of blood [glucose] in patients with diabetes.

Oxidation of Nonmuscle Lipid

Most stored energy is in the form of triacylglycerols. In the prototypical 70-kg person, adipocytes store ~132,000 kcal of potential energy (see Table 58-1 ). The mobilization of lipid from adipocytes (see p. 1182 ) during exercise is largely under the control of the sympathetic nervous system, complemented by the release of growth hormone during exercise lasting >30 to 40 minutes. The result of this mobilization is an increase in circulating levels of fatty acids, which can enter skeletal muscle—especially type I and IIa fibers (see Fig. 60-5 ).

Not only do fatty acids released from adipocytes enter muscle via the circulation, but skeletal muscle itself stores several thousand kilocalories of potential energy as intracellular triacylglycerols, which contribute to fatty-acid oxidation.

In the presence of adequate O ₂ , fatty acids provide up to 60% of the oxidized fuel supply of muscle during prolonged exercise. The oxidation of fatty acids (see pp. 1183–1185 ), such as palmitate in the following example, has a very high yield of ATP:

Lipids are an important source of energy when O ₂ is available; that is, during prolonged low- to moderate-intensity activity and during recovery following exercise.