Structure of Skeletal Muscle: Physiological Aspects

Introduction

• Skeletal muscle contraction is organized at the level of the sarcomere, where coordinated interaction of actin and myosin produces shortening. Electrical signals via T tubules trigger calcium release, enabling cross-bridge cycling, while calcium reuptake restores relaxation and structural integrity.

• Muscles convert chemical energy into mechanical force to produce movement.
• They transform electrical or chemical signals into a coordinated mechanical response.
• An increase in intracellular calcium ions acts as the primary trigger for contraction.
• Based on structure and function, muscles are classified into skeletal, smooth, and cardiac types.
• Skeletal muscle is attached to bones and enables body movement through joint actions. Its activity is largely voluntary and controlled by motor neurons. It produces rapid and powerful contractions when stimulated.
• Skeletal muscle can sustain force for moderate durations but is susceptible to fatigue. Its functional properties allow precise and controlled movements.

Structure Of Skeletal Muscle

• Skeletal muscle is composed of multiple bundles called fascicles, arranged in parallel.
• Each fascicle contains numerous elongated muscle fibers aligned for coordinated contraction.
• The entire muscle is surrounded by a connective tissue layer called epimysium.
• Each fascicle is enclosed by the perimysium, which also carries blood vessels and nerves.
• Individual muscle fibers are wrapped by a delicate layer known as endomysium.
• These connective tissue layers consist of collagen and elastic fibers that provide support.
• They also help transmit contractile force from muscle fibers to bones.
• Muscles are attached to bones through tendons, which are strong collagenous structures.

Myocyte

• A myocyte is a single skeletal muscle cell and the structural unit of muscle. Its cell membrane is called the sarcolemma, and the cytoplasm is termed sarcoplasm.
• Muscle fibers are long, cylindrical, and multinucleated, extending along the length of the muscle.
• Their diameter ranges from about 10 to 100 micrometers, and length may reach up to 20 centimeters.
• Nuclei are initially central during development but become peripherally placed beneath the sarcolemma after maturation.
• The sarcolemma conducts electrical impulses across the entire muscle fiber. It ensures uniform spread of depolarization to initiate contraction. It also provides protection and contributes to elastic resistance during stretch.
• Absence of gap junctions maintains electrical independence between adjacent muscle fibers.

Myofibrils and Organelles

• The sarcoplasm contains numerous myofibrils arranged parallel to the long axis of the muscle fiber.
• Myofibrils extend from one end of the fiber to the other and attach to tendons.
• Each myofibril is about one micrometer in diameter and consists of repeating contractile units.
• These units contain thick and thin filaments, responsible for muscle contraction.
• Thick filaments are primarily composed of myosin, while thin filaments contain actin and regulatory proteins.
• The sarcoplasm also contains essential organelles such as mitochondria, known as sarcosomes.
• The sarcoplasmic reticulum stores and releases calcium ions during contraction.
• The Golgi apparatus and other organelles support protein synthesis and cellular maintenance.
• Skeletal muscle shows characteristic striations due to alternating dark and light bands.
• The dark band, called the A band, contains thick filaments.
• The light band, called the I band, contains thin filaments.
• Each myofibril is organized into repeating units called sarcomeres.

Development of Myocytes

• Muscle fibers develop during fetal life by fusion of myoblasts, which are mononucleated precursor cells.
• This fusion results in formation of long, multinucleated muscle fibers.
• After birth, muscle fibers do not increase in number but grow in size.
• Growth from infancy to adulthood mainly occurs by hypertrophy.
• Following injury, existing muscle fibers have limited ability to divide.
• Repair is mediated by satellite cells located adjacent to muscle fibers.
• These cells can differentiate into new muscle cells under appropriate conditions.
• However, regeneration may be incomplete in severe damage.
• Remaining fibers often undergo hypertrophy to compensate for functional loss.

Muscle Proteins

• Skeletal muscle contains three major protein groups: contractile, regulatory, and attachment proteins.
• Contractile proteins include myosin and actin, which generate force.
• Regulatory proteins control interaction between filaments.
• Attachment proteins maintain structural alignment and stability of the sarcomere.

Contractile Proteins

• The primary contractile proteins are myosin and actin.
• Myosin forms the thick filaments, while actin forms the thin filaments.

Myosin

• Myosin forms the thick filaments of skeletal muscle and is composed of myosin II molecules.
• Each molecule contains two intertwined heavy chains and four light chains.
• The structure includes two globular heads, a neck region, and a long tail.
• The heads project outward in a helical arrangement, forming cross-bridges.
• These heads interact with actin and play a key role in force generation during contraction.

Myosin Head

• The myosin head is formed by the amino terminal region of a heavy chain associated with two light chains. It contains binding sites for actin and adenosine triphosphate.
• The adenosine triphosphate binding site functions as an adenosine triphosphatase, providing energy for contraction.
• The alkali light chain stabilizes the head, while the regulatory light chain modulates enzymatic activity.

Myosin Tail

• The myosin tail is formed by coiling of heavy chains into a long rod-like structure.
• Tails align along the axis of the thick filament, forming its backbone.
• The globular heads project outward, forming cross-bridges that interact with actin.

Myosin Hinge

• The hinge region connects the head and tail and provides flexibility.
• This flexibility allows the head to move during the contraction cycle.
• Myosin molecules are arranged in a bipolar pattern within the thick filament.
• Their tails face the center, forming a region without heads.
• The heads project outward on both sides, enabling interaction with thin filaments.
• The M line marks the region where polarity reverses and helps maintain alignment.
• Structural proteins such as titin and myomesin stabilize this organized arrangement.

Actin

• Actin forms the thin filaments of skeletal muscle and is essential for contraction.
• The filamentous form, called F-actin, is composed of repeating globular G-actin units.
• G-actin monomers join end to end and twist into a double helical structure.
• This helical arrangement provides strength and flexibility to the thin filament.
• Each G-actin molecule contains binding sites for myosin and regulatory proteins.
• These sites are crucial for interaction during cross-bridge formation.
• The protein nebulin runs along the length of the filament and regulates its size.
• The helical structure creates a longitudinal groove that accommodates tropomyosin.
• Tropomyosin lies along the filament and helps regulate access to binding sites.
• A typical thin filament contains several hundred actin molecules and associated regulatory proteins.

Regulatory Proteins

• Regulatory proteins control interaction between actin and myosin during muscle contraction.
• The two main regulatory proteins are tropomyosin and troponin.

Tropomyosin

• Tropomyosin is a long, rod-shaped protein located in the groove of the actin filament. It extends along the length of actin and covers myosin-binding sites.
• In the resting state, it prevents interaction between actin and myosin.
• This inhibition maintains the muscle in a relaxed condition.

Troponin

• Troponin is a complex of three subunits: troponin T, troponin I, and troponin C.

Troponin T

• Troponin T has molecular weight 30,000. Troponin T attaches the complex to tropomyosin.

Troponin I (MW 22,000)

• Troponin I binds to actin and inhibits interaction with myosin in the resting state.

Troponin C (MW 18,000)

• Troponin C binds calcium ions and triggers structural changes.
• Calcium binding removes inhibition, allowing actin–myosin interaction and initiation of muscle contraction.

Note:

Interaction of troponin with tropomyosin:

• Each troponin complex is associated with one tropomyosin molecule on the actin filament.
• One tropomyosin molecule covers approximately seven actin monomers.
• Troponin also interacts directly with actin. This arrangement regulates exposure of myosin-binding sites and controls muscle contraction.

Attachment Proteins

• Attachment proteins maintain structural alignment of myofilaments and transmit force during contraction.

Titin

• Titin is a large elastic protein extending from the Z line to the M line. It stabilizes thick filaments and maintains the central position of the A band. It also prevents excessive stretching of the sarcomere.

Nebulin

• Nebulin runs along the length of thin filaments. It regulates and stabilizes the length of actin filaments during development.

Alpha Actinin

• Alpha actinin anchors thin filaments firmly to the Z line.

Desmin

• Desmin is an intermediate filament protein that connects adjacent myofibrils. It links the Z line to the sarcolemma, ensuring structural integrity.

Dystrophin

• Dystrophin connects actin filaments to membrane proteins and the extracellular matrix. It facilitates transmission of contractile force to surrounding tissues.
• Defects in dystrophin lead to muscle degeneration and weakness.

Myomesin

• Myomesin is located at the M line. It binds myosin filaments and maintains alignment of thick filaments within the sarcomere.

Sarcomere

• The sarcomere is the structural and functional unit of a myofibril. It consists of a repeating arrangement of thick and thin filaments.
• Sarcomeres are arranged in series along the length of each myofibril.
• Each sarcomere extends between two adjacent Z lines.
• The average length of a sarcomere is about two micrometers.

Structure

• The sarcomere shows a highly organized pattern responsible for muscle contraction.

Z Line

• The Z line is a dense protein structure oriented perpendicular to the muscle fiber. It serves as the anchoring point for thin filaments.
• Thin filaments are attached to the Z line through alpha actinin.
• Z lines also help align adjacent myofibrils within the muscle fiber.

Thin Filament

• Each thin filament measures about one micrometer in length and seven nanometers in diameter. It is composed of actin, tropomyosin, and troponin in a specific proportion.
• Thin filaments extend from the Z line toward the center of the sarcomere.
• They overlap partially with thick filaments, enabling interaction during contraction.
• Each sarcomere contains two sets of thin filaments, one from each end. This organized arrangement allows efficient force generation during muscle contraction.

Thick Filament and A Band

• The A band represents the central dark region of the sarcomere formed by thick filaments.
• Each thick filament is about 1.6 micrometers long and 10 nanometers in diameter.
• Thick filaments are composed mainly of myosin molecules arranged in parallel.

I Band

• The I band is the light region containing only thin filaments without overlap. It lies between adjacent A bands and is bisected by the Z line.
• During contraction, the I band shortens as thin filaments slide inward.
• The length of the A band remains constant, so sarcomere shortening depends on I band reduction.

H Band

• The H band is a lighter region within the center of the A band. It contains only thick filaments and no overlap with thin filaments.
• This zone becomes narrower or disappears during contraction.

M Line

• The M line is located at the center of the H band. It contains proteins that hold thick filaments together and maintain alignment.
• Titin connects thick filaments to the Z line and contributes to elastic stability.
• This arrangement ensures proper positioning of filaments within the sarcomere.

Hexagonal and triangular arrangement:

• In cross-section, each thick filament is surrounded by six thin filaments in a hexagonal pattern.
• Each thin filament is surrounded by three thick filaments in a triangular arrangement.
• This geometric organization maximizes interaction between filaments.

Cross-Bridges

• Cross-bridges are projections formed by myosin heads extending toward actin filaments.
• These structures attach to actin during contraction.

Sarcotubular System

• The sarcotubular system is a network of membranous structures surrounding myofibrils within muscle fibers. It consists of the sarcoplasmic reticulum and transverse tubules.
• This system is closely related to the arrangement of A and I bands and is essential for excitation–contraction coupling.

Structure

• It consists of sarcoplasmic reticulum and T (transverse) tubules (Fig. 26.15).

T-tubules

• T-tubules are tubular invaginations of the sarcolemma with a diameter of about 0.03 micrometers.
• They penetrate deep into the muscle fiber and surround myofibrils at the A–I junction.
• Their lumen contains extracellular fluid continuous with the surrounding environment.
• Action potentials travel along the sarcolemma and enter the cell interior through T-tubules.
• This ensures rapid and uniform activation of deep myofibrils.

Sarcoplasmic Reticulum

• The sarcoplasmic reticulum is a specialized form of endoplasmic reticulum in muscle cells. It forms an extensive network around each myofibril and runs parallel to myofilaments.
• Tubules have narrow segments with enlarged regions called terminal cisternae.
• Terminal cisternae lie adjacent to T-tubules at the A–I junction.
• The combination of one T-tubule and two cisternae forms a triad.
• This structure links electrical excitation to calcium release for contraction.
• In cardiac muscle, a similar arrangement forms a diad with one cisterna.

Receptors and Channel Proteins in STS

• The T-tubule and terminal cisternae are separated by a narrow gap containing junctional structures called feet.
• These junctions involve interaction between proteins on both membranes.
• The T-tubule membrane contains dihydropyridine receptors, which are voltage-sensitive channels.
• These receptors are arranged in groups called tetrads.
• They primarily function as voltage sensors rather than channels for calcium entry.
• The terminal cisternae contain ryanodine receptors, which act as calcium release channels.
• Activation of these receptors causes rapid release of calcium into the sarcoplasm.
• The sarcoplasmic reticulum membrane also contains calcium adenosine triphosphatase pumps.
• These pumps actively transport calcium back into the reticulum after contraction.
• This coordinated system ensures precise regulation of calcium during muscle contraction and relaxation.

Functions

Role of STS in Muscle Contraction and Relaxation

• The sarcotubular system links electrical excitation to mechanical contraction in muscle fibers.
• Action potentials traveling through T-tubules trigger calcium release from the sarcoplasmic reticulum.
• Increased cytoplasmic calcium activates the contractile proteins.
• Reuptake of calcium into the sarcoplasmic reticulum lowers intracellular calcium levels.
• This leads to muscle relaxation. Thus, the system regulates both contraction and relaxation efficiently.

Mechanism of Calcium Release

• Depolarization at the motor end plate generates action potentials that spread along the sarcolemma and into T-tubules.
• This electrical signal reaches the triad region and activates dihydropyridine receptors in the T-tubule membrane.
• These receptors undergo conformational change and interact with ryanodine receptors on the sarcoplasmic reticulum.
• Ryanodine receptor channels open, releasing calcium from terminal cisternae into the cytoplasm.
• The rise in cytoplasmic calcium initiates cross-bridge cycling and muscle contraction.
• This sequence of events is termed excitation–contraction coupling.
• A small amount of calcium may also enter from extracellular fluid through T-tubule channels. This can further stimulate calcium release from the sarcoplasmic reticulum, known as calcium-induced calcium release. This mechanism plays a limited role in skeletal muscle but is important in cardiac muscle.
• Localized increases in calcium concentration near release sites are called calcium sparks.

Mechanism of Calcium Uptake

• The sarcoplasmic reticulum contains SERCA pumps, which actively transport calcium from the cytoplasm into the reticulum.
• These pumps use energy from adenosine triphosphate to move calcium against its concentration gradient.
• Approximately two calcium ions are transported for each molecule of adenosine triphosphate hydrolyzed.
• Pump activity increases when cytoplasmic calcium concentration rises after contraction.
• Within the terminal cisternae, calcium binds to calsequestrin, allowing storage at high concentration.
• This buffering prevents excessive free calcium accumulation inside the reticulum.
• Reduction in cytoplasmic calcium concentration leads to cessation of cross-bridge activity. This process initiates muscle relaxation and restores the resting state of the fiber.

Functions of STS

• The sarcotubular system transmits action potentials from the surface to deep myofibrils. It increases cytoplasmic calcium concentration by releasing calcium from the sarcoplasmic reticulum. It promotes muscle relaxation through calcium reuptake into the reticulum.
• The terminal cisternae serve as important calcium storage sites.