ORGANIZATION OF SKELETAL MUSCLE

The skeletal muscle is an intricately organised tissue con­sisting of bundles of muscle fibres called myofibres, illus­trated in Figure 7.3.

Each myofibre is a cylindrical muscle cell ranging from 5 to 100 μm in diameter and around 10 to 30 centimetres in length.

The muscle fibre is the contractile unit that shortens and transmits a pull through the endomysium, perimysium, and epimysium to the tendon or aponeurosis attached to a

FIGURE 7.1 Control of muscle movement for posture adjust­ment. Arrows show the direction of joint movement.

FIGURE 7.2 Diagram showing striations in the skeletal muscle. bone, thereby eliciting movement. Several hundred to sev­eral thousand myofibrils are arranged in parallel along the length of each muscle fibre; it looks like each layer is super­imposed on another.

7.3.1 Arrangement of Myofibrils

Each myofibril comprises a linear sequence of repeating sarcomeres (Figure 7.5), which are the fundamental con­tractile units of the muscle fibre and can number in the tens of thousands.

The sarcomere contains a disk at each end known as the Z disk. The sarcomere comprises a range of large protein molecules responsible for muscular contraction, many of which are polymerised. Numerous thin protein filaments known as actin are attached to the Z disks and extend

FIGURE 7.3 Diagram showing the organisation of skeletal mus­cle at multiple levels.

towards the centre of the sarcomere, resembling parallel fingers pointing at each other. These filaments are arranged in a regular spatial pattern, with a 2:1 ratio of actin to myo­sin. The actin filaments of two sarcomeres, common to the same Z line, form an I band or light bands. On the other hand, the myosin filaments are centrally located within a sarcomere and provide the dark bands (A band) of the characteristic striations along with the overlay of actin fila­ments. The myosin and actin filaments partially interdigi­tate, causing the myofibrils to have alternate light and dark bands. The dark bands or A bands are composed of myosin filaments and the overlapping ends of actin filaments, which exhibit anisotropic behaviour towards polarised light. This arrangement of actin and myosin filaments gives skeletal and cardiac muscle their striated appearance.

Each actin filament is made up of two helical strands of actin protein and two of tropomyosin protein, which are intertwined together as a larger helical complex. Troponin, complex globular protein molecules, are located intermit­tently along the tropomyosin-actin strand and can bind tropomyosin and actin. They have an affinity for calcium (Ca2+) ions. Myosin protein polymers in the form of thick filaments are present in suspension between the thin fila­ments of actin, running parallel to them. Approximately 500 myosin heads of a thick myosin filament form cross-bridges

FIGURE 7.5 Diagram shows the sarcomere and the arrange­ment of actin and myosin filaments in it. Actin and myosin fila­ments are arranged parallel to one another.

FIGURE 7.4 Skeletal muscle insertion in the bone and multi-level organization.

that interact with actin to shorten the sarcomere as the myo­sin heads flex and relax.

7.3.2 Contractile Proteins

Myosin is a thick filament present in the sarcomere. Each myosin molecule has a molecular weight of approximately 480,000 and is composed of six polypeptide chains, includ­ing two heavy chains and four light chains, as seen in Figure 7.6.

The myosin molecule consists of two heavy chains, each weighing approximately 200,000, which twist around each other to form a double helix called the tail. At one end of the double helix, there are two free myosin heads, each consist­ing of a globular polypeptide structure and two light chains of molecular weight 20,000 each, which help control the function of the head during muscle contraction. The fila­ment of myosin is constructed by bundling together over 200 individual myosin molecules, with the tails of these molecules forming the body of the filament. The heads of each myosin molecule, along with the protruding arms, form cross-bridges, which are flexible at two points called hinges. These hinged arms and heads play a crucial role in the contraction process, extending the heads far outward from the body of the myosin filament or bringing them close to the body. The myosin filaments are uniform in length, about 1.6 micrometres, and twisted to ensure cross­bridges extend in all directions. Additionally, there are no cross-bridge heads in the centre of the myosin filament for a distance of about 0.2 micrometres due to the extension of the hinged arms away from the centre or H zone. The myo­sin head plays a critical role in muscle contraction by func­tioning as an ATPase enzyme that hydrolyses ATP. This action allows the head to harness the energy released from the high-energy phosphate bond of ATP and use it to power the contraction process.

The structural core of the actin filament is a double helix of F-actin protein, depicted by the two lighter strands in the referenced Figure 7.7.

This helical structure is similar to that of the myosin molecule. The F-actin molecule comprises two helical strands with G-actin molecules with a molecular weight of approximately 42,000.

FIGURE 7.6 Molecular structure of myosin. Two heavy chains form the tail of myosin, while two light chains form the head along with each heavy chain.

FIGURE 7.7 Molecular arrangement of actin is formed by two helical structures of F-actin. Tropomyosin strands fit in the groove formed by the helical structure of F-actin, which covers active binding sites.

the actin-tropomyosin strand and contains binding sites for tropomyosin, actin, and calcium ions.

7.3.3 Regulatory Proteins

Tropomyosin, a protein component of the actin filament, has a molecular weight of 70,000 and is 40 nanometres long. It spirals around the F-actin helix (See Figure 7.7). When the muscle is at rest, tropomyosin covers the active sites on the actin strands, preventing interaction with myo­sin and, thus, muscle contraction. Tropomyosin undergoes a structural change due to a signal, which consequently exposes the active sites on actin and initiates contraction.

Troponin intermittently attaches along the tropomyosin and is a complex protein of three subunits, each having a specific function in muscle contraction control. Troponin I binds to actin, troponin T binds to tropomyosin, and tropo­nin C has a high affinity for calcium ions.

Regulatory role of troponin and tropomyosin in muscle contraction: The troponin-tropomyosin complex inhibits the actin filament. Actin filaments, along with magnesium ions and ATP, swiftly and securely bind to the myosin molecule heads in the absence of the troponin-tropomyosin complex. However, when the troponin-tropomyosin complex is intro­duced to the actin filament, it prevents the binding between myosin and actin. In a relaxed muscle, the active sites on the normal actin filament are physically covered by the troponin-tropomyosin complex, which hinders them from attaching to the myosin filament heads and initiating mus­cle contraction. To initiate contraction, the inhibitory effect of the troponin-tropomyosin complex must be neutralised.

The inhibitory effect of the troponin-tropomyosin com­plex on the actin filaments is itself suppressed by a sub­stantial quantity of calcium ions. The exact way in which the inhibition occurs is not fully comprehended. Still, one

FIGURE 7.8 Diagram shows the sarcomere and the arrangement of the Sarcotubular system. T Tubules are formed by invagination of the sarcolemma, and L tubules (sarcoplasmic reticulum) are parallel to sarcomere.

possible explanation is that when calcium ions attach to troponin C, the troponin complex undergoes a structural modification that leads to pulling on the tropomyosin mole­cule, causing it to move deeper into the gap between the two strands of actin. This movement exposes the active sites of the actin, allowing them to attract the myosin cross-bridge heads and facilitating the onset of contraction. While this mechanism is theoretical, it highlights the alteration of the normal interaction between the troponin-tropomyosin com­plex and actin by calcium ions, leading to a new state that triggers contraction.

7.3.4 Anchoring Proteins

Actinin is a structural protein that anchors actin filaments to the Z-discs, maintaining sarcomere integrity and actin alignment during muscle contraction. Desmin, a type III intermediate filament, supports muscle cells by linking Z-discs, myofibrils, and the cell membrane. Desmin is vital in preserving the structural stability of muscle cells and transmitting contractile forces across the muscle tissue. Nebulin, a large protein, is a molecular ruler, regulating actin filament length and organisation. The largest protein, Titin, provides passive elasticity, maintaining sarcomere integrity and regulating muscle tension.

7.3.5 Sarcotubular System

The skeletal muscle fibres harbour an intricate network of tubules known as the sarcotubular system, playing a cru­cial role in muscle function. Two distinct tubule sets com­pose this system, each with a unique arrangement among the myofibrils. The sarcoplasmic reticulum, encircling myofibrils, consists of tubules parallel to the myofibrils. In contrast, T tubules, arranged transversely, extend from one side of the fibre to the other, regularly spaced to serve each sarcomere, as shown in Figure 7.8.

The sarcotubular system facilitates impulse conduction from the muscle fibre surface to its core, with the sarcoplas­mic reticulum serving as a vital calcium ion storage site, influencing muscle contraction initiation and termination. This intricate structure ensures anastomosing channel-like connectivity around each myofibril.

The system is further elucidated through the classifi­cation of two primary structures: T tubules and L tubules (sarcoplasmic reticulum). T tubules, formed by sarcolemma invaginations, penetrate the muscle fibre, allowing extracel­lular fluid flow through their lumen. In contrast, L tubules, or longitudinal tubules, constitute the sarcoplasmic reticu­lum, forming a closed tubular system around each myofi­bril. At regular intervals, L tubules dilate into lateral sacs called terminal cisternae, creating triads with adjacent T tubules. Triads are situated at the junction between ‘A’ and ‘I’ bands in skeletal muscle. L tubules store calcium ions, crucial for muscle contraction, and play a pivotal role in excitation-contraction coupling. The functions of the sar- cotubular system are delineated through the roles of T and L tubules. T tubules ensure the rapid transmission of action potentials from the sarcolemma to myofibrils, facilitating efficient muscle stimulation. On the other hand, L tubules store a substantial quantity of calcium ions, releasing them into the sarcoplasm upon action potential arrival at the cis­ternae. This release of calcium ions initiates the processes essential for muscle contraction, highlighting the critical role of the sarcotubular system in the intricate mechanism of muscle function.

FIGURE 7.9 Diagram shows a schematic representation of the neuromuscular junction and receptors of acetylcholine on the sarcolemma.

7.4