The 3 types of muscle fiber found in humans are , fast-twitch, slow-twitch, & intermediate.

Lactate Shuttles to the Mitochondria, Oxidative Fibers, or Liver

The fastest muscle fibers are expected to produce lactic acid at the highest rate. The first method of removing lactic acid is through mitochondria in the same cells that produce it. The lactic acid is taken up into the mitochondria by the MCT1 and the lactic acid is converted to pyruvate and oxidized. This intracellular shuttle is shown in Figure 3.7.5. When lactic acid production outstrips the capacity of lactic acid to be metabolized within the fast-twitch muscles, it spills out into the extracellular space. Some of this lactate is taken up by oxidative fibers, which are generally smaller than the large glycolytic fibers. Thus some of the lactic acid produced and released by muscle is metabolized in the muscle itself. This constitutes the cell–cell shuttle, also shown in Figure 3.7.5.

The liver can take up lactate that is released into the blood by the active muscles. The liver either metabolizes the lactate for energy or uses it to make new glucose through gluconeogenesis, and exports the glucose into the blood. Muscles can then take up this glucose and use it again for energy. This cycle of blood glucose to muscle lactate to blood lactate to liver lactate and back to blood glucose is called the Cori cycle, shown in Figure 3.7.5.

NMJs Differ in Structure and Function

NMJs on fast and slow muscle fibers, such as those on the fast EDL and slow SOL of the rat, differ both in structure and function. Presynaptically, fast nerve endings and slow nerve endings arborize differently, and fast nerve endings contain more terminal swellings (varicosities). The fast endings release more acetylcholine at the onset of impulse trains, but since they have smaller vesicle pools, they fatigue more easily as release runs down faster during continued stimulation. Postsynaptically, relative to slow NMJs, fast NMJs have denser, deeper, and more branched infoldings. They also respond to given doses of ACh with larger postsynaptic currents. In their synaptic clefts, fast NMJs contain predominantly the large A12 form of AChE, whereas slow NMJs contain more of the smaller A8 and A4 forms. The AChE molecules are anchored to the synaptic basal lamina by one of two types of collagen-tailed proteins encoded by different transcripts from the same ColQ gene in fast and slow muscle fibers. Two distinct promoters for the ColQ gene have been identified; these are differentially expressed in fast and slow muscle fibers. The promoter present in slow fibers is activated by the transcription factor called nuclear factor of activated T cells (NFAT) at a ‘slow upstream regulatory element’ (SURE), whereas the promoter expressed in fast fibers contains a ‘fast intronic regulatory element’ (FIRE). Assuming that different compositions of AChE isoforms reflect differences in function, such findings suggest that the fast and slow impulse patterns transmitted by fast and slow NMJs pose different demands on AChE function.

a Aerobic and Anaerobic Energy Metabolism

In general, fast-twitch muscle fibers in the untrained state are biochemically suited to derive energy for contraction by anaerobic glyco(geno)lysis. Fast-twitch fibers, particularly type IIx, tend to have higher concentrations of glycogen and creatine phosphate as well as higher activities of enzymes associated with glycogenolysis and glycolysis (Table 15-1). Slow-twitch type I fibers, on the other hand, generally have higher concentrations of triglycerides and myoglobin and are better suited to derive their energy by oxidative phosphorylation via the electron transport system following the oxidation of fatty acids and glucose via the Krebs cycle (Table 15-1). Type IIa fibers are intermediate in their glycolytic and oxidative capacity between type IIx and type I fibers (Adhihetty et al., 2003; Rubenstein and Kelly, 2004).

Triglycerides and glycogen serve as primary substrates for muscle metabolism. In general, the rate of glycogen utilization is greatest with high-intensity anaerobic exercise, whereas low-intensity submaximal exercise results in a lower rate of glycogen utilization and reliance on oxidation of fatty acids as fuel (Kiens, 2006). Under conditions of restricted energy intake or prolonged exercise, amino acids may also serve as energy substrates within skeletal muscle (Rennie et al., 2006).

Regional Variation in Myotomal Muscle Properties

Myotomal muscle contractile properties vary between fiber types, with position on the body axis and among developmental stages. Force production and shortening by skeletal muscle are caused by myosin cross-bridge cycling. This requires adenosine triphosphate (ATP) energy and the binding and release of Ca2+ from troponin C, a protein component of thick myosin filament. Muscle shortening velocities decrease in the order white > pink > red in concert with a decreasing myosin-ATPase content. Factors affecting the Ca2+ occupancy of troponin-binding sites and the rates of cross-bridge attachment and detachment change the rates of muscle activation, shortening, and relaxation. Differences in the rates of activation, shortening, and relaxation can occur independently as they are influenced by separate muscle proteins.

Both red and white muscle fibers in a number of teleost species have slower rates of activation and/or relaxation moving along the body axis from anterior to posterior. These differences have been correlated with longitudinal changes in the expression of three muscle proteins: parvalbumin, troponin T, and the myosin light chain (MLC; specifically MLC2 the regulatory light chain). Regional differences have been found in the relative amount of these proteins and/or in the relative proportions of alternate protein isoforms:

Binding of Ca2+ to troponin C is an essential step intriggering cross-bridge cycling and muscle contraction. Parvalbumin binds free Ca2+ in the myoplasm, competing with troponin C. Parvalbumin, therefore, influences muscle relaxation by reducing the concentration of free Ca2+ in the myoplasm. High parvalbumin concentrations should be associated with rapid muscle relaxation. Parvalbumin content declines from anterior to posterior in trout (Oncorhynchus mykiss), sheepshead (Archosargus probatocephalus), and kingfish (Menticirrhus americanus) red band white muscle, and in cod (Gadus morhua) and largemouth bass (Micropterus salmoides) white muscle, likely being a factor in increased relaxation times moving from anterior to posterior in these species.

Troponin T is a component of muscle thin filaments (see also DESIGN AND PHYSIOLOGY OF THE HEART | Cardiac Excitation–Contraction Coupling: Calcium and the Contractile Element). It is thought to affect the rate at which Ca2+ dissociates from troponin C, and therefore the rate at which muscle relaxes. The relative proportions of two troponin T isoforms shift from anterior to posterior in cod (G. morhua) and largemouth bass (M. salmoides), with the dominant anterior form likely having faster kinetics than the alternate isoform.

MLC2 is a thick filament component that may modulate cross-bridge kinetics by controlling sensitivity to Ca2+. The amounts of the slow MLC2 isoform increase, moving from anterior to posterior in both the slow and fast muscle of rainbow trout (O. mykiss).

The list of regionally variable proteins that influence myotomal muscle contractile properties is likely to grow as more data become available. Fewer data are available for elasmobranchs, but similar regional differences in contractile properties have not yet been detected.

In addition to regional mechanical differences, there is also variation in the extent to which fish muscle fibers rely on either aerobic or anaerobic metabolic pathways to supply energy for contraction. The volume fraction of red fibers occupied by mitochondria is typically greater than 25% compared with less than 10% in white muscle. Accordingly, the activities of mitochondrial enzymes associated with aerobic metabolism, such as cytochrome oxidase and citrate synthase, are higher in red than in white muscle. Pink muscle shows an intermediate level of activity for these enzymes. White muscle relies primarily on anaerobic glycolysis for its energy supply, as indicated by higher levels of glycolytic enzymes, such as phosphofructokinase, than found in red or pink muscle.

2.2 Types of Muscle Fibers

Slow-twitch and fast-twitch muscle fibers have already been addressed briefly; here we discuss them in detail. Muscle is comprised of different muscle fibers, which differ in appearance and other characteristics. For instance, comparing muscle isolated from a wild and a domestic rabbit, the wild one is more reddish in color. Also when comparing chicken breast to thigh, the latter is more reddish than the breast.

Thus, muscle that is exposed to constant activity (such as the muscle of a wild rabbit, and the thighs of the chicken) is reddish, and composed of slow-twitch muscle fibers, whereas muscles which are not exposed to constant exertion (muscle of a domesticated rabbit, and chicken breast) are lighter in color and are composed of fast-twitch muscle fibers. The occurrence of muscle fibers depends on exertion, innervation, and the type of innervation. Inside a muscle there may appear different type of muscle fibers—for instance, closer to the bones, muscles are more reddish than close to the surface. Generally speaking, extensors contain more fast-twitch muscle fibers than flexors do. There are muscles in the human body that are comprised mainly of either slow-twitch or fast-twitch muscle fibers. Muscle fibers are innervated by alpha motor neurons. The motor neuron and all the muscle fibers to which it connects is a motor unit. The number of muscle fibers innervated by one motor neuron can differ; for instance, in extraocular muscles, 10 muscle fibers are innervated by one motor neuron, while thigh muscles can have 1000 fibers in each unit. The axons of the motor neurons of the spinal cord innervate the peripheral muscles, and they can have a length of more than 1 m (Fig. 2.9).

Motor units differ according to size and activation threshold. Large motor units have higher activation thresholds and contain paler fast-twitch muscle fibers, while small motor units have lower activation thresholds and contain reddish slow-twitch muscle fibers. Differences in physiological, biochemical, histochemical, and genetic characteristics of motor units also provide a useful base to distinguish between them (Table 2.2).

Table 2.2. Characteristics of muscle fibers

Based on physiological characteristics, human muscle fibers are fast fatigable, fast fatigue resistant, fast intermediate, or slow fibers; based on biochemical properties they are fast glycolytic type IIb fibers, fast oxidative- glycolytic type IIa fibers, or slow oxidative type I fibers. Another classification gives another type of fibers, IIi fibers, with characteristics between type IIa and IIb. The red slow-twitch fibers contain high amounts of iron, which come from the higher number of mitochondria and myoglobin content. The red fibers have higher oxidative capacity; they are able to consume high amounts of oxygen and reduce it in the mitochondria. Oxygen is always bound to iron-containing molecules; this high iron content also contributes to its red color. Table 2.2 shows the differences between the types of muscle fibers. The differences in activation threshold determine the activation order of the different fiber types in contraction. Slow-twitch muscle fibers with their excellent oxygen consumption rate and high mitochondria content and oxidative enzyme activity are the most efficient fibers. They are able to generate force at the point of contraction because of their low activation threshold. Most fibers of antigravity muscles are slow-twitch fibers, and these fibers are involved during walking and low intensity movements. One of the main laws in nature is profitability, which in this case means the engagement of the more profitable muscle fibers first. Fast-twitch muscle fibers with their higher activation thresholds and huge force generation are usable during flight and survival; however, these fibers consume a lot of energy and produce a lot of lactic acid (discussed later). They can only be activated by high intensity stimuli because of the higher threshold. To use an analogy, slow-twitch fibers are like economic city cars, while fast-twitch muscle fibers are like high-powered racing cars.

Mechanical Properties during Contraction and at Rest: Sarcomeric Motors and Cytoskeleton

The scarce daily amount of activity of the fast muscle fibers is closely related to their contractile specialization, as such fibers are able to develop high tension and high mechanical power and are, therefore, employed for rapid and strong movements. In contrast, slow fibers are employed in tasks requiring less power and tension, but are specialized to minimize energy expenditure and to avoid fatigue. The molecular basis of the specialized contractile performance can be found in the specific isoforms of sarcomeric proteins expressed by fast and slow fibers (Figure 60.4). Actually, the conversion of the chemical energy of ATP into mechanical energy (work) and heat occurs at different rates depending mainly on the specific myosin isoforms. Fast fibers, with their subtypes 2A, 2X, and 2B, develop more tension than slow fibers during maximal contraction (50,51) and, if allowed to shorten, reach a higher speed of shortening against any given load, thus producing different force velocity curves (50) (Figure 60.5A). Also, mechanical power, which is the rate of generation of work and is the most relevant parameter for limb or body movement, reaches different values in relation to the myosin isoform expressed by the fibers (Figure 60.5B). The values of both shortening velocity and peak power progressively increase from slow to fast 2A, fast 2X, and fast 2B. The ATP hydrolysis rate also differs between slow and fast fibers. The cost of tension development in ATP is much lower in slow than in fast fibers (53,54), while the ATP hydrolysis rate during shortening is approximately in proportion to power output and this implies a similar efficiency of chemo-mechanical energy conversion regardless of myosin isoform expression (55). On the whole, the mechanical and energetic parameters of the contractile response make slow fibers more suitable for low intensity and long-lasting activity and fast fibers for short and strong contractile performance.

The myofibrils, where myosin and actin interaction produce force and movement, are part of the cytoskeleton, i.e. the cellular scaffolding responsible not only for determining the shape and size (length) of muscle fibers, but also for transmitting the force and movement to the extracellular fibrous skeleton. Diversity among fibers is also detectable in the cytoskeleton, in particular in transversal protein aggregates forming the Z-discs, M-bands, and in longitudinally oriented sarcomeric giant proteins (titin and nebulin) (Figure 60.4). Slow fibers have thicker Z-discs and M-band, a feature that is probably related to the ability to withstand active force (56). Titin, the major determinant of resting tension, is present in slow fibers with longer and more extensible isoforms, thus allowing passive elongation with less mechanical resistance compared to fast fibers (different resting tension-length curve and viscoelasticity) (57). Slow fibers are also characterized by longer nebulin and actin filaments, which might imply that active tension-length curve and optimal length are shifted towards longer sarcomere length (57,58). It is worth recalling that, although fast fibers develop higher tension during isometric contractions, the difference disappears in eccentric contractions where the highest forces are generated (59). In such conditions, the ability to withstand tension without damage is greater in slow than in fast fibers (60).

Fast versus Slow Muscle Gene Regulation

In adult muscle, Six1 and Eya1 are accumulated in fast muscle fibers, and ectopic overexpression of these factors in the slow-type soleus muscle results in a conversion of the slow oxidative phenotype to a fast glycolytic phenotype. Higher activity of Six1/Eya1in fast-type fibers is seen immediately postnatally, suggesting that it may have a precocious role in the activation of the fast-type programme, prior to slow/fast motor neuron activity.

A transcriptome analysis in the embryo shows that many genes encoding fast muscle isoforms are downregulated in the remaining myotome of Six1/4 double mutants. The binding of Six1/4 to regulatory regions of fast muscle genes supports direct regulation by these factors in the embryo as well as the adult (3). In the mouse, both fast and slow isoforms are co-expressed in embryonic muscle cells. This is in contrast to the situation in the zebrafish, for example, where there is an early segregation of fast and slow muscle progenitors. In this case, Hedgehog signaling induces the transcriptional repressor, Prdm1/Blimp1, in adaxial cells, preventing the activation of fast muscle genes and of the gene for Sox6, a repressor of slow-type gene transcription, therefore conferring a slow phenotype on these cells. Prdm1 is expressed in the mouse myotome, but mutants do not have a fast phenotype, reflecting differences in regulation of slow muscle genes; in myotomal cells. Sox6 null embryos only show upregulation of slow muscle gene expression at fetal stages (4).

4.3 Motor Units and Force Generation

There is a significant difference between slow-twitch and fast-twitch muscle fibers, as discussed in Chapter 2, in their activation threshold and force generation. A question arises regarding why motor units need to be distinguished from the whole muscle. Unlike in cardiac muscle where all the cardiac cells are working as one syncytium and there are no motor units, in skeletal muscle, motor units (muscle fibers innervated by a single neuron) are recruited and activated. Force generation by skeletal muscle is several hundredfold greater than by that of cardiac muscle, which requires complex innervation. Recruitment and synchronicity of motor units can be measured by electromyography (EMG); however, the types of motor units can only be determined indirectly based on physiological characteristics such as fatigue and extent of force. As mentioned before, characteristics of muscle depend on innervation, which can be modified to a limited extent. Recruitment of motor units starts with the small ones, which generate the least force, and is followed by motor units that are greater in size and generate a significant force (Zajac and Faden, 1985). This indicates that recruitment of motor units aligns with power necessary for a movement; for instance, no recruitment of large motor units occurs if 5% force is necessary for a movement assuring profitability. When huge power is needed, in addition to fatigue-resistant motor units, other fatigable motor units with higher activation thresholds are recruited. Thus, force generation increases with the recruitment of motor units in a nonlinear manner since force generation by the different units is not equal. The correlation is exponential since motor units with the greatest force generation ability are recruited last (Fig. 4.1).

Force generated by different muscle fibers differs significantly even if a muscle, e.g., the soleus, contains mainly slow-twitch fibers; force generation falls between 31 and 1600 mN (McDonagh et al., 1980). This difference can be extreme in the case of a muscle comprised of mainly fast-twitch fibers, e.g., the tibialis anterior. It should be noted that force generation can differ between the same types of motor fibers, which can be monitored by EMG, where fiber types are reflected by activation frequency. The abovementioned activation order can be seen in slow movements, whereas in fast movements task-dependent recruitment has been observed. In latter case, e.g., learned movements, fast motor units can be recruited earlier regardless of normal activation order (Herrmann and Flanders, 1998). This observation emphasizes the potential usefulness of smooth automatic movements in explosive strength training. This will be further discussed at explosive strength training.

pH

Goat muscle contains both aerobic (red) and anaerobic (white) muscle fibers and undergoes the same postmortem biochemical changes as beef and mutton. The decline of goat muscle pH follows a pattern typical of red meat carcasses to stabilize at around pH 5.4. Variations occur due to differences between muscles, sexes, and premortem stress. Exhaustive premortem stress yields dark, firm, and dry meat with a high ultimate pH (pH > 6.0). Postmortem biochemical changes are associated with the loss of water-binding capacity as the pH reaches the isoelectric point of the muscle proteins, the onset of rigor mortis, and the release and activation of proteolytic enzymes, notably cathepsins, responsible for the ripening of meat.

Effect on skeletal muscle

Excessive amounts of glucocorticoids induce muscle wasting, i.e., marked reduction in muscle volume, particularly in fast-twitch muscle fibers (Christy, 1971; Askari et al., 1976). The onset of these changes is usually gradual and often requires weeks or months to develop. Glucocorticoids preferentially affect the proximal muscles; however, the distal muscles are also affected with prolonged exposure to high doses of glucocorticoids. Differential effect of glucocorticoids on synthesis and degradation of muscle-contractile proteins, such as the myosin light and heavy chains, were reported (Seene, 1994; Almon and Dubois, 1990; Rooyackers and Nair, 1997).