Premed · Premed · Anatomy Physiology 1
Lecture 10: Muscle Tissue — Structure and Contraction
Anatomy and Physiology I
Learning Objectives
By the end of this lecture, students will be able to:
- Describe the macroscopic and microscopic anatomy of skeletal muscle
- Explain the organization of a skeletal muscle from the whole muscle to the molecular level
- Describe the structure of a sarcomere and identify its bands and zones
- Explain the sliding filament model of muscle contraction
- Describe the events at the neuromuscular junction
- Outline the steps of excitation-contraction coupling
- Describe the cross-bridge cycle
- Explain how a muscle relaxes
Lecture Content
I. Overview of Skeletal Muscle Functions
Skeletal muscle serves several essential functions in the body. It produces movement, including locomotion, facial expression, and breathing. It maintains posture and body position by generating continuous low-level contractions. It stabilizes joints by reinforcing them through muscle tone. It generates heat through thermogenesis, accounting for approximately 85 percent of body heat. It also guards body openings through the action of sphincters.
II. Macroscopic Anatomy of Skeletal Muscle
Connective Tissue Coverings (from outermost to innermost)
Skeletal muscle is organized by three layers of connective tissue. The epimysium is a layer of dense irregular connective tissue surrounding the entire muscle. The perimysium is fibrous connective tissue surrounding each fascicle, which is a bundle of muscle fibers. The endomysium is a thin, delicate connective tissue layer surrounding each individual muscle fiber (cell). These connective tissue layers are continuous with each other and with the tendons or aponeuroses that attach muscle to bone. They also provide pathways for blood vessels and nerves to reach the muscle fibers.
Blood and Nerve Supply
Each muscle fiber is supplied by a capillary and innervated by a branch of a motor neuron. Skeletal muscles are richly vascularized because of their high metabolic demand. Each skeletal muscle is served by at least one nerve containing both motor and sensory fibers.
Attachments
Muscles attach to bones at two points. The origin is the attachment to the less movable bone, typically the proximal one, while the insertion is the attachment to the more movable bone, typically the distal one. Attachments can be made via tendons, which are rope-like cords of dense regular connective tissue, or aponeuroses, which are flat, sheet-like tendons.
III. Microscopic Anatomy of Skeletal Muscle
The Muscle Fiber (Cell)
Skeletal muscle fibers are very large, cylindrical, multinucleated cells formed during development by the fusion of many embryonic myoblasts. The nuclei are located at the periphery of the cell, just beneath the sarcolemma. Individual fibers range from 10 to 100 micrometers in diameter and can be up to 30 centimeters or more in length.
Key Structural Features
The sarcolemma is the plasma membrane of the muscle fiber. The sarcoplasm, or cytoplasm, contains abundant glycogen as an energy reserve and myoglobin, an oxygen-binding protein similar to hemoglobin. T-tubules (transverse tubules) are deep invaginations of the sarcolemma that penetrate into the cell interior, conducting action potentials from the cell surface deep into the fiber and ensuring that the signal reaches all parts of the fiber simultaneously.
The sarcoplasmic reticulum (SR) is an elaborate network of smooth endoplasmic reticulum surrounding each myofibril. It stores and releases calcium ions (Ca2+) upon stimulation. The terminal cisternae are enlarged regions of the SR flanking each T-tubule, and a triad consists of one T-tubule plus two flanking terminal cisternae (one on each side).
Myofibrils are long, cylindrical organelles that run the length of the muscle fiber and are composed of repeating contractile units called sarcomeres. Each muscle fiber contains hundreds to thousands of parallel myofibrils, which are the actual contractile elements.
Myofilaments and the Sarcomere
Myofibrils are composed of two types of protein filaments called myofilaments. Thick filaments are composed primarily of myosin. Each myosin molecule has a tail and two globular heads (cross-bridges). The myosin heads have ATPase activity, enabling them to hydrolyze ATP, and possess binding sites for actin. Approximately 300 myosin molecules make up each thick filament, with heads projecting outward in all directions.
Thin filaments are composed primarily of actin. F-actin consists of two twisted strands of globular actin (G-actin) monomers resembling a double string of pearls, and each G-actin monomer has a myosin-binding site. Two regulatory proteins are associated with the thin filament. Tropomyosin is a long, thread-like protein wound around the actin helix that blocks the myosin-binding sites when the muscle is at rest. Troponin is a globular regulatory protein complex bound to tropomyosin at regular intervals, consisting of three subunits: troponin T (TnT), which binds to tropomyosin; troponin I (TnI), the inhibitory subunit that holds tropomyosin in its blocking position; and troponin C (TnC), which binds calcium ions and initiates the conformational change that exposes the binding sites.
The Sarcomere — The Functional (Contractile) Unit
The sarcomere is the repeating unit of a myofibril, extending from one Z disc to the next. The Z disc (Z line) is a protein disc anchoring the thin filaments at each end of the sarcomere, and the M line is a protein line in the center anchoring the thick filaments. The bands and zones visible under microscopy as striations are as follows. The A band (dark band) spans the length of the thick filaments and includes zones of overlap with thin filaments; it does NOT change length during contraction. The I band (light band) contains only thin filaments, spans adjacent sarcomeres on either side of a Z disc, and shortens during contraction. The H zone is the lighter central region of the A band containing only thick filaments with no overlap, and it shortens or disappears during contraction. The zone of overlap is where thick and thin filaments overlap, and it is the region where cross-bridges form and force is generated.
Several additional structural proteins help maintain sarcomere integrity. Titin is a giant elastic protein extending from the Z disc to the M line that holds thick filaments in position and provides elasticity and recoil. Nebulin wraps around thin filaments and maintains their alignment. Dystrophin links thin filaments to the sarcolemma via a complex of integral membrane proteins, transferring force to the extracellular matrix. Absence or deficiency of dystrophin causes Duchenne muscular dystrophy.
<image>A multi-level diagram of skeletal muscle organization. Panel A: A whole muscle covered by epimysium, cut open to show fascicles wrapped in perimysium, with individual muscle fibers wrapped in endomysium. Panel B: A single muscle fiber (cell) with peripheral nuclei beneath the sarcolemma, containing parallel myofibrils. A cross-section shows the arrangement of thick and thin filaments in a hexagonal pattern. Panel C: A detailed sarcomere diagram between two Z discs, showing thick filaments (myosin, in the center spanning the A band) and thin filaments (actin, anchored at the Z discs). The I band, A band, H zone, M line, and zone of overlap are labeled. Panel D: Molecular detail of the thin filament showing the actin double helix, tropomyosin coiled along the groove, and troponin complexes at regular intervals. A myosin molecule is shown with its tail and two globular heads (cross-bridges).</image>
IV. The Neuromuscular Junction (NMJ)
The neuromuscular junction is the synapse between a motor neuron and a skeletal muscle fiber. Each skeletal muscle fiber is innervated by a single motor neuron, though one motor neuron may innervate many fibers. A motor unit consists of one motor neuron plus all the muscle fibers it innervates.
Structure of the NMJ
The axon terminal (synaptic knob) contains synaptic vesicles filled with the neurotransmitter acetylcholine (ACh). The synaptic cleft is a narrow gap of approximately 50 nanometers between the axon terminal and the muscle fiber. The motor end plate is the specialized region of the sarcolemma at the NMJ, highly folded into junctional folds that increase surface area. It contains abundant ACh receptors (nicotinic receptors, which are ligand-gated Na+ channels) and acetylcholinesterase (AChE), an enzyme in the synaptic cleft and on the junctional folds that rapidly breaks down ACh to terminate the signal.
Events at the NMJ
The sequence of events at the neuromuscular junction proceeds as follows. An action potential arrives at the axon terminal, causing voltage-gated Ca2+ channels to open so that Ca2+ enters the terminal. The influx of Ca2+ triggers exocytosis of synaptic vesicles, releasing ACh into the synaptic cleft. ACh then binds to nicotinic ACh receptors on the motor end plate, opening the ligand-gated Na+ channels so that Na+ rushes in (and some K+ rushes out). This local depolarization produces an end-plate potential (EPP), which is always large enough to reach threshold. An action potential is then generated on the sarcolemma adjacent to the end plate and propagates across the entire sarcolemma and down the T-tubules. Meanwhile, ACh is rapidly broken down by AChE into acetate and choline, and the choline is taken back up into the axon terminal to resynthesize ACh. Each nerve impulse releases enough ACh to produce a response, making the NMJ a reliable synapse that requires no summation.
<image>A detailed diagram of the neuromuscular junction. A motor neuron axon terminal is shown approaching a skeletal muscle fiber. The axon terminal contains mitochondria and synaptic vesicles filled with ACh. The synaptic cleft separates the terminal from the motor end plate (a specialized region of the sarcolemma with deep junctional folds). Nicotinic ACh receptors are concentrated on the crests of the folds. AChE molecules are shown in the cleft. Numbered steps show: (1) action potential arriving, (2) Ca2+ entering through voltage-gated channels, (3) vesicle fusion releasing ACh, (4) ACh binding to receptors, (5) Na+ influx through opened channels, (6) action potential generation on the sarcolemma. An inset shows a magnified ACh receptor with its Na+ channel pore.</image>
V. Excitation-Contraction Coupling
Excitation-contraction coupling is the sequence of events by which an action potential on the sarcolemma leads to cross-bridge activity and muscle contraction. It links the electrical event (excitation) to the mechanical event (contraction).
Steps
The process begins when the action potential propagates along the sarcolemma and down the T-tubules into the interior of the fiber. T-tubule depolarization activates voltage-sensitive receptors (dihydropyridine receptors / DHP receptors) in the T-tubule membrane. These DHP receptors are mechanically coupled to ryanodine receptors (RyR), which are Ca2+ release channels on the terminal cisternae of the sarcoplasmic reticulum. When the ryanodine receptors open, stored Ca2+ floods from the SR into the sarcoplasm, causing the Ca2+ concentration to rise dramatically — approximately 100-fold. The released Ca2+ binds to troponin C on the thin filaments, causing troponin to undergo a conformational change that shifts tropomyosin away from the myosin-binding sites on actin. With the myosin-binding sites now exposed, cross-bridge cycling can begin.
VI. The Cross-Bridge Cycle
The cross-bridge cycle is the repeating sequence of events by which myosin heads pull thin filaments toward the center of the sarcomere, generating force.
In the first step, cross-bridge formation, the energized myosin head (with ADP + Pi bound) attaches to the exposed binding site on actin, forming a cross-bridge. In the second step, the power stroke, the myosin head pivots, pulling the thin filament toward the M line as ADP and Pi are released. Each power stroke slides the thin filament approximately 10 nanometers, and the sarcomere shortens as the I band and H zone narrow. In the third step, cross-bridge detachment, a new molecule of ATP binds to the myosin head, causing it to detach from actin. Without ATP, the myosin head cannot detach, which explains rigor mortis — the stiffening of muscles after death when ATP is depleted. In the fourth step, myosin reactivation (cocking), myosin ATPase hydrolyzes the ATP to ADP + Pi, and the energy released re-energizes (cocks) the myosin head, returning it to its high-energy position ready to bind actin again.
The cycle repeats as long as Ca2+ and ATP are available. During a single contraction, each myosin head may go through the cycle approximately five times per second. Many cross-bridges cycle asynchronously — some pulling while others are resetting — ensuring smooth, continuous movement.
VII. The Sliding Filament Model of Contraction
According to the sliding filament model, thin filaments slide past thick filaments toward the center of the sarcomere during contraction. Neither thick nor thin filaments change length; instead, the sarcomere shortens as the Z discs are pulled closer together. The observable changes during contraction are as follows: the I bands narrow as thin filaments are pulled inward, the H zone narrows or disappears as thin filaments overlap more with thick filaments, the A band remains the same width because the thick filaments do not change length, and the overall sarcomere length decreases. The shortening of all sarcomeres in all myofibrils of a fiber produces whole-fiber contraction.
VIII. Muscle Relaxation
Muscle relaxation occurs through a defined sequence. The motor neuron stops firing and ACh release ceases. AChE rapidly breaks down the remaining ACh in the synaptic cleft, and action potentials cease on the sarcolemma. Ca2+-ATPase pumps (SERCA pumps) on the SR then actively transport Ca2+ back into the SR, a process that requires ATP. As Ca2+ concentration in the sarcoplasm drops, Ca2+ detaches from troponin C, and tropomyosin returns to its blocking position, covering the myosin-binding sites on actin. Cross-bridge cycling stops because no new cross-bridges can form. The muscle fiber returns to its resting length passively through the elastic recoil of titin, connective tissue elements, and the contraction of opposing muscles.
<image>A four-step diagram of the cross-bridge cycle shown in a sarcomere context. Step 1 (Cross-bridge formation): An energized myosin head (with ADP + Pi) binds to an exposed actin binding site. Step 2 (Power stroke): The myosin head pivots toward the M line, pulling the thin filament; ADP and Pi are released. Step 3 (Cross-bridge detachment): A new ATP molecule binds to the myosin head, causing it to release from actin. Step 4 (Myosin reactivation): ATP is hydrolyzed to ADP + Pi, re-energizing the myosin head back to its cocked position, ready to bind again. Arrows connect the four steps in a circular cycle. A side panel shows a sarcomere at rest (long, with wide I bands and H zone) versus contracted (short, with narrow I bands and H zone), demonstrating the sliding filament model.</image>
