Anatomy and Physiology of the Musculo-skeletal System

The muscular-skeletal system is the system that is mainly important in locomotion, body support and makes bodies’ frame work. It consists of skeletal muscles, bones and joints.

Our bodies contain three distinct types of muscle tissue, each uniquely adapted to perform specific roles. While all muscle tissues share the ability to contract, they differ significantly in their location, microscopic appearance (histology), and physiological function.

• Location:
  • Attached to bones (or to skin, as in facial muscles).
  • Forms the bulk of the body's muscle mass.
• Histology (Microscopic Appearance):
  • Striated: Appears striped or banded under a microscope due to the arrangement of contractile proteins (actin and myosin).
  • Very long, cylindrical cells (fibers): Can be several centimeters long.
  • Multinucleated: Each muscle fiber contains many nuclei, located peripherally (just under the sarcolemma, or cell membrane).
  • Voluntary: Contraction is under conscious control.
• Function:
  • Movement: Responsible for all voluntary movements of the body (e.g., walking, lifting, speaking, facial expressions).
  • Posture: Maintains body posture.
  • Stabilize Joints: Helps stabilize joints by exerting tension.
  • Heat Generation: Produces heat as a byproduct of contraction, helping to maintain body temperature.

• Location:
  • Found exclusively in the wall of the heart (myocardium).
• Histology (Microscopic Appearance):
  • Striated: Like skeletal muscle, it also appears striped due to the arrangement of contractile proteins.
  • Branched cells: Individual cells are shorter than skeletal muscle fibers and branch, forming an intricate network.
  • Uninucleated (or occasionally binucleated): Each cell usually has one (sometimes two) centrally located nuclei.
  • Intercalated Discs: Unique to cardiac muscle, these are specialized junctions between adjacent cardiac muscle cells. They contain desmosomes (to prevent cells from pulling apart) and gap junctions (to allow ions to pass quickly, enabling rapid communication and synchronized contraction).
  • Involuntary: Contraction is not under conscious control; it's regulated by the heart's intrinsic pacemaker and influenced by the autonomic nervous system.
• Function:
  • Pump Blood: Responsible for pumping blood throughout the body, maintaining blood pressure and circulation.

• Location:
  • Found in the walls of hollow internal organs (viscera), except the heart.
  • Examples: Walls of the digestive tract (stomach, intestines), urinary bladder, respiratory passages (bronchi), arteries, veins, uterus, arrector pili muscles in the skin (causing "goosebumps").
• Histology (Microscopic Appearance):
  • Non-striated: Lacks the visible banding pattern seen in skeletal and cardiac muscle because the contractile proteins are arranged more randomly.
  • Spindle-shaped cells: Elongated cells with tapered ends.
  • Uninucleated: Each cell contains a single, centrally located nucleus.
  • Involuntary: Contraction is not under conscious control; it's regulated by the autonomic nervous system, hormones, and local factors.
• Function:
  • Peristalsis: Propels substances along internal passageways (e.g., food through the digestive tract).
  • Regulation of Organ Volume: Can maintain prolonged contractions, regulating the size of organs (e.g., constricting blood vessels, emptying the bladder).
  • Movement of Fluids: Moves fluids and other substances within the body.
  • Regulates Airflow: Adjusts the diameter of respiratory passages.

Skeletal muscles are truly fascinating structures, responsible for all voluntary movements, from the subtlest facial expressions to powerful athletic feats. They are unique among muscle types due to their voluntary control and striated appearance.

Skeletal muscles are organs composed predominantly of muscle tissue, but they also contain connective tissues, nerves, and blood vessels. They are typically attached to bones, and this attachment is crucial for their function in generating movement.

1. Muscle Belly: This is the fleshy, contractile part of the muscle. It contains thousands to hundreds of thousands of individual muscle fibers (cells).
2. Attachments to Bones: Skeletal muscles connect to bones, usually at two points:
   • Origin: This is typically the less movable (or stationary) attachment point of the muscle. It often lies closer to the trunk or center of the body.
   • Insertion: This is the more movable attachment point of the muscle. When the muscle contracts, the insertion point is pulled towards the origin, causing movement at a joint.
3. Example: For the biceps brachii muscle in your upper arm:
   • Origin: Scapula (shoulder blade)
   • Insertion: Radius (forearm bone)
   • When the biceps contracts, it pulls the radius towards the scapula, causing the elbow to bend (flex).
4. Connective Tissue Attachments: Muscles attach to bones via specialized connective tissues:
   • Tendons: These are cord-like bundles of dense regular connective tissue. They are continuous with the connective tissue sheaths within and around the muscle and then with the periosteum (the fibrous membrane covering the bone). This direct continuity ensures that the force generated by muscle contraction is effectively transmitted to the bone, causing movement. Tendons are incredibly strong and relatively inelastic.
   • Aponeuroses: These are broad, flat sheets of dense regular connective tissue. They function similarly to tendons, serving as a flat attachment site, especially where muscles are broad and require a wide area of attachment, or where they connect to other muscles. Examples include the aponeurosis of the external oblique muscle in the abdomen, or the plantar aponeurosis in the sole of the foot.

Understanding the hierarchical organization of skeletal muscle is key to appreciating how force is generated and transmitted. It's like a cable, where smaller strands are bundled together to form larger, stronger cables.

1. Entire Muscle (Organ Level):
   • This is what we commonly recognize as "a muscle" (e.g., biceps brachii, quadriceps femoris).
   • It is composed of many bundles of muscle fibers, along with connective tissue, blood vessels, and nerves.
   • The entire muscle is typically enclosed by a dense, irregular connective tissue sheath called the epimysium.
2. Fascicle (Bundle of Muscle Fibers):
   • The entire muscle is divided into numerous smaller bundles called fascicles.
   • Each fascicle consists of anywhere from 10 to 100 or more individual muscle fibers.
   • Each fascicle is wrapped in its own connective tissue sheath, the perimysium. This compartmentalization allows for independent neural control of different parts of a muscle.
3. Muscle Fiber / Muscle Cell (Cellular Level):
   • Within each fascicle are the individual muscle cells, which are often referred to as muscle fibers due to their elongated, cylindrical shape.
   • These are unique cells: they are very long (can be up to 30 cm in large muscles), multinucleated (containing many nuclei), and are the actual contractile units.
   • Each muscle fiber is surrounded by a delicate connective tissue layer called the endomysium.
   • The plasma membrane of a muscle fiber is called the sarcolemma, and its cytoplasm is called the sarcoplasm.
4. Myofibril:
   • Inside each muscle fiber (muscle cell), the sarcoplasm is packed with hundreds to thousands of rod-like structures called myofibrils.
   • Myofibrils are the actual contractile elements of the muscle cell. They are composed of even smaller structures called myofilaments.
   • The characteristic "striated" or striped appearance of skeletal muscle under a microscope is due to the repeating arrangement of these myofilaments within the myofibrils.
5. Myofilaments (Actin & Myosin):
   • These are the protein filaments that make up the myofibrils. They are the actual contractile proteins.
   • Thick filaments are primarily composed of the protein myosin.
   • Thin filaments are primarily composed of the protein actin, along with regulatory proteins troponin and tropomyosin.
   • These myofilaments are organized into functional repeating units called sarcomeres.

Skeletal muscles are not just bundles of contractile cells; they are highly organized structures held together and protected by various layers of connective tissue. These sheaths play vital roles in transmitting force, providing pathways for nerves and blood vessels, and maintaining the structural integrity of the muscle.

These connective tissue layers are continuous with each other and ultimately with the tendons, forming a continuous network that effectively transmits the force generated by the contracting muscle fibers to the bones, enabling movement.

A skeletal muscle fiber, or muscle cell, is a highly specialized and elongated cell designed for contraction. It has several unique features that distinguish it from a typical animal cell.

1. Sarcolemma (Plasma Membrane):
   • Description: This is the specialized plasma membrane of a muscle fiber. It is a thin, elastic membrane that encloses the sarcoplasm.
   • Function:
     • Electrical Excitability: It has voltage-gated ion channels that allow it to generate and propagate action potentials (electrical signals).
     • Invaginations (T-tubules): At numerous points, the sarcolemma invaginates deep into the muscle fiber to form structures called Transverse Tubules (T-tubules).
2. Sarcoplasm (Cytoplasm):
   • Description: This is the cytoplasm of a muscle fiber. It contains the usual organelles found in other cells, but also has some specialized components.
   • Specialized Components:
     • Glycosomes: Granules of stored glycogen, which provide glucose for ATP production.
     • Myoglobin: A red pigment that stores oxygen, similar to hemoglobin in blood. Myoglobin efficiently stores oxygen within the muscle cell, providing an oxygen reserve for aerobic respiration during periods of high activity.
     • Mitochondria: Numerous mitochondria are packed between the myofibrils, reflecting the high energy demand of muscle contraction (producing ATP).
     • Myofibrils: The most prominent component, myofibrils are rod-like contractile elements that make up about 80% of the muscle fiber volume.
3. Sarcoplasmic Reticulum (SR) (Endoplasmic Reticulum):
   • Description: This is a highly specialized, elaborate network of smooth endoplasmic reticulum that surrounds each myofibril like a loosely woven sleeve. It runs longitudinally along the myofibril. At the A-I band junction, it forms larger, perpendicular channels called terminal cisternae.
   • Function:
     • Calcium Storage and Release: The primary function of the SR is to store and regulate the intracellular concentration of calcium ions (Ca2+). It contains a high concentration of Ca2+ pumps that actively transport Ca2+ from the sarcoplasm into the SR, and Ca2+ release channels that open in response to electrical signals.
     • Excitation-Contraction Coupling: The release of Ca2+ from the SR is the critical step that initiates muscle contraction.
4. T-Tubules (Transverse Tubules):
   • Description: These are deep, invaginations (inward extensions) of the sarcolemma that run perpendicular to the long axis of the muscle fiber. They are located at the A-I band junction of each sarcomere.
   • Function:
     • Rapid Impulse Transmission: T-tubules act as rapid communication channels, allowing the electrical impulse (action potential) generated on the sarcolemma to quickly penetrate deep into the muscle fiber, reaching every sarcomere.
     • Coupling with SR: Each T-tubule runs between two terminal cisternae of the SR, forming a structure called a triad. This close anatomical arrangement is crucial for excitation-contraction coupling, as the electrical signal in the T-tubule directly triggers Ca2+ release from the adjacent SR terminal cisternae.
5. Nuclei (Multinucleated):
   • Description: Unlike most cells, skeletal muscle fibers are multinucleated, meaning they contain many nuclei. These nuclei are typically located just beneath the sarcolemma (peripherally).
   • Function: Protein Synthesis: The large number of nuclei allows for the efficient production of the vast amounts of proteins (especially contractile proteins like actin and myosin) needed for the maintenance and repair of the very long muscle fiber, as well as for muscle growth (hypertrophy).

Myofibrils are the long, cylindrical, contractile organelles found within the sarcoplasm of a muscle fiber. It's their precise arrangement of protein filaments that gives skeletal muscle its characteristic striated appearance and enables contraction.

1. Myofibrils and Sarcomeres:
   • Each myofibril is composed of a chain of repeating contractile units called sarcomeres.
   • A sarcomere is the fundamental functional unit of a skeletal muscle, extending from one Z disc to the next Z disc. It is the smallest unit of a muscle fiber that can contract.
   • The precise arrangement of two types of myofilaments within each sarcomere creates the striations.
2. Myofilaments:
   • Thick Filaments (Myosin Filaments): Composed primarily of the protein myosin. Each myosin molecule has a "rod-like" tail and two globular "heads." The heads are crucial for muscle contraction, as they bind to actin and possess ATPase activity. They are found in the center of the sarcomere and do not extend the entire length of the sarcomere.
   • Thin Filaments (Actin Filaments): Composed primarily of the protein actin, which forms a double helix. Also contains two regulatory proteins:
     • Tropomyosin: A rod-shaped protein that spirals around the actin core, blocking the myosin-binding sites on actin in a relaxed muscle.
     • Troponin: A three-polypeptide complex that binds to actin, tropomyosin, and calcium ions (Ca2+). Its binding of Ca2+ causes a conformational change that moves tropomyosin away from the myosin-binding sites.
     Thin filaments extend from the Z disc toward the center of the sarcomere.
3. Bands and Zones within a Sarcomere: The alternating dark and light bands give skeletal muscle its striated appearance.
   • Z Disc (Z Line): A coin-shaped sheet of proteins (primarily alpha-actinin) that anchors the thin filaments and connects myofibrils to one another. It defines the lateral boundaries of a single sarcomere.
   • I Band (Light Band): A lighter region on either side of the Z disc. Contains only thin filaments (actin). During contraction, the I band shortens.
   • A Band (Dark Band): A darker, central region of the sarcomere. Contains the entire length of the thick filaments (myosin). Also contains the inner ends of the thin filaments that overlap with the thick filaments. The A band's length does not change significantly during contraction.
   • H Zone (H Band): A lighter region within the center of the A band. Contains only thick filaments (myosin); there is no overlap with thin filaments in a relaxed muscle. During contraction, the H zone shortens and can even disappear as thin filaments slide past.
   • M Line: A dark line in the exact center of the H zone (and thus the A band). Consists of proteins (e.g., myomesin) that anchor the thick filaments in place and keep them aligned.

During muscle contraction, the thin filaments slide past the thick filaments, pulling the Z discs closer together. This causes the sarcomere to shorten, and the I bands and H zones to narrow or disappear, while the A band's length remains relatively constant. This mechanism is known as the Sliding Filament Model of Contraction.

The Sliding Filament Model is the universally accepted explanation for how skeletal muscles contract. It states that during contraction, the thin filaments (actin) slide past the thick filaments (myosin), causing the sarcomere to shorten. The myofilaments themselves do not shorten; rather, their overlap increases.

Here's a breakdown of the key principles:

1. Relaxed State:
   • In a relaxed muscle fiber, the thick and thin filaments overlap only slightly at the ends of the A band.
   • The H zone (containing only thick filaments) and the I band (containing only thin filaments) are at their maximum width.
   • The myosin heads are "cocked" and energized, but they are prevented from binding to actin by the regulatory protein tropomyosin, which covers the myosin-binding sites on the actin molecules.
2. Initiation of Contraction (The Signal):
   • A nerve impulse (action potential) arrives at the neuromuscular junction (which we'll detail later).
   • This electrical signal is transmitted down the sarcolemma and into the T-tubules.
   • The signal in the T-tubules triggers the release of calcium ions (Ca2+) from the sarcoplasmic reticulum (SR) into the sarcoplasm.
3. Role of Calcium (Ca2+) and Regulatory Proteins:
   • When Ca2+ is released into the sarcoplasm, it binds to the regulatory protein troponin.
   • Binding of Ca2+ causes troponin to change shape.
   • This shape change in troponin, in turn, pulls the tropomyosin molecule away from the active (myosin-binding) sites on the actin filament.
   • With the binding sites now exposed, the myosin heads are free to attach to actin.
4. Cross-Bridge Formation (Myosin-Actin Binding):
   • The energized myosin heads (which have already hydrolyzed ATP into ADP and inorganic phosphate, storing the energy) bind to the exposed active sites on the actin filament, forming cross-bridges.
5. The Power Stroke:
   • Once the myosin head is attached to actin, the stored energy is released, causing the myosin head to pivot or "bend." This bending motion is called the power stroke.
   • The power stroke pulls the thin filament (actin) toward the M line (the center of the sarcomere).
   • As the myosin head pivots, it releases ADP and inorganic phosphate.
6. Cross-Bridge Detachment:
   • A new ATP molecule then binds to the myosin head.
   • The binding of ATP causes the myosin head to detach from the actin filament. This detachment is crucial; without new ATP, the cross-bridges would remain attached, leading to a state known as rigor mortis (stiffening after death due to lack of ATP).
7. Cocking of the Myosin Head:
   • The newly bound ATP is immediately hydrolyzed (broken down) by the ATPase enzyme on the myosin head into ADP and inorganic phosphate (Pi).
   • This hydrolysis provides the energy to "re-cock" or re-energize the myosin head, returning it to its high-energy, ready-to-bind position.
8. Repetition of the Cycle:
   • As long as Ca2+ is present and bound to troponin (keeping the actin binding sites exposed) and sufficient ATP is available, the cycle of cross-bridge formation, power stroke, and detachment will repeat multiple times.
   • Each cycle pulls the thin filament a little further toward the M line.
9. Sarcomere Shortening:
   • With each power stroke, the thin filaments slide further inward.
   • This sliding action shortens the sarcomere (the distance between Z discs).
   • As all the sarcomeres in a myofibril shorten simultaneously, the entire myofibril shortens, which in turn causes the entire muscle fiber and ultimately the entire muscle to shorten, generating force and producing movement.

These four proteins are the molecular machinery that directly drives and regulates muscle contraction.

1. Actin (Thin Filament Component):
   • Structure: Actin forms the "backbone" of the thin filaments. It's a globular protein (G-actin) that polymerizes to form long, fibrous strands (F-actin), which then twist together into a double helix.
   • Role in Contraction: Actin contains the active (myosin-binding) sites. It is the protein that the myosin heads attach to and pull on during the power stroke. Actin essentially provides the "track" along which myosin travels.
   • Key Action: Binds to myosin heads to form cross-bridges.
2. Myosin (Thick Filament Component):
   • Structure: Myosin is a large motor protein that makes up the thick filaments. Each myosin molecule has a long tail and two globular heads. The heads contain an actin-binding site and an ATPase (enzyme that breaks down ATP) site.
   • Role in Contraction: Myosin is the "motor" protein. Its heads bind to actin, pivot (power stroke) to pull the actin filament, and then detach. The ATPase activity in the heads hydrolyzes ATP, providing the energy for these movements.
   • Key Action: Forms cross-bridges with actin, pulls actin filaments, hydrolyzes ATP for energy.
3. Tropomyosin (Regulatory Protein of Thin Filament):
   • Structure: A rod-shaped protein that spirals around the actin filament, covering the active (myosin-binding) sites on the actin molecules in a relaxed muscle.
   • Role in Contraction: Its primary role is to block the myosin-binding sites on actin in a relaxed muscle. This prevents myosin from binding to actin and initiating contraction when the muscle is not stimulated.
   • Key Action: Blocks actin's active sites, preventing contraction in the absence of calcium.
4. Troponin (Regulatory Protein of Thin Filament):
   • Structure: A complex of three globular polypeptides, each with a specific function:
     • TnI (inhibitory): Binds to actin, holding the troponin-tropomyosin complex in place.
     • TnT (tropomyosin-binding): Binds to tropomyosin, helping to position it on the actin filament.
     • TnC (calcium-binding): Binds to calcium ions (Ca2+).
   • Role in Contraction: Troponin is the calcium sensor that initiates the unblocking of actin. When calcium ions become available (released from the sarcoplasmic reticulum), they bind to the TnC subunit. This binding causes a conformational change in troponin, which then pulls tropomyosin away from the myosin-binding sites on actin.
   • Key Action: Binds calcium, causing tropomyosin to move off the actin binding sites, thereby allowing myosin to bind.

The neuromuscular junction (NMJ) is the specialized synapse where a motor neuron communicates with a skeletal muscle fiber. It's the critical link that translates a nerve impulse into a muscle action potential.

Here's the sequence of events at the NMJ:

1. Action Potential Arrives at the Axon Terminal: A nerve impulse, or action potential (AP), travels down the motor neuron axon and reaches the axon terminal (also called the synaptic knob or terminal bouton), which is the enlarged end of the motor neuron.
2. Voltage-Gated Calcium Channels Open:
   • The arrival of the action potential at the axon terminal depolarizes the membrane, opening voltage-gated calcium (Ca2+) channels in the presynaptic membrane (the membrane of the axon terminal).
   • Ca2+ ions, which are in higher concentration outside the cell, rush into the axon terminal.
3. Acetylcholine (ACh) Release:
   • The influx of Ca2+ into the axon terminal triggers the fusion of synaptic vesicles (which contain the neurotransmitter acetylcholine, ACh) with the presynaptic membrane.
   • Acetylcholine (ACh) is then released into the synaptic cleft (the tiny space between the axon terminal and the muscle fiber). This release occurs via exocytosis.
4. ACh Binds to Receptors on the Motor End Plate:
   • ACh diffuses across the synaptic cleft and binds to specific nicotinic acetylcholine receptors located on the motor end plate of the muscle fiber. The motor end plate is a specialized region of the sarcolemma that is highly folded to increase surface area and contains a high density of these receptors.
   • These receptors are ligand-gated ion channels.
5. Ion Channels Open and Local Depolarization (End Plate Potential):
   • The binding of ACh to its receptors causes the ligand-gated ion channels to open.
   • These channels allow both sodium ions (Na+) to flow into the muscle fiber and potassium ions (K+) to flow out.
   • However, more Na+ enters than K+ leaves, resulting in a net influx of positive charge. This causes a local depolarization of the motor end plate, called an end plate potential (EPP).
6. Generation of Muscle Action Potential:
   • If the end plate potential reaches a critical threshold, it triggers the opening of voltage-gated sodium channels in the adjacent sarcolemma (the sarcolemma immediately outside the motor end plate).
   • A rapid influx of Na+ through these voltage-gated channels generates a full-blown muscle action potential.
   • This action potential then propagates (travels) along the entire sarcolemma and deep into the muscle fiber via the T-tubules.
7. Termination of ACh Activity:
   • To prevent continuous muscle contraction, the effects of ACh must be rapidly terminated. This is achieved by the enzyme acetylcholinesterase (AChE), which is located in the synaptic cleft and on the sarcolemma.
   • AChE breaks down ACh into its components (acetic acid and choline), rendering it inactive.
   • This rapid degradation ensures that each nerve impulse produces only one muscle action potential.