Muscle Physiology

A‑band

the dark central region of a sarcomere where thick (myosin) filaments overlap with thin (actin) filaments. Its length stays constant during contraction because the thick filaments do not change length; only the degree of overlap with actin varies.

Actin (G‑/F‑actin)

• the primary protein of the thin filament in all striated and many smooth muscles. In its soluble form it exists as G‑actin (globular monomer); when many G‑actin molecules polymerize head‑to‑tail they form the long, helical F‑actin (filamentous) strand that makes up the backbone of the thin filament.

• G‑actin = globular monomer that polymerizes into F‑actin (filamentous).

• F‑actin forms the thin filament, providing the binding sites for myosin heads. Calcium‑bound troponin shifts tropomyosin, exposing these sites for cross‑bridge formation.

Acetylcholinesterase

An enzyme located in the synaptic cleft of the neuromuscular junction that rapidly hydrolyzes acetylcholine into choline and acetate, terminating the neural signal and allowing the sarcolemma to repolarize. Muscle contraction can relax

Ca²⁺‑induced Ca²⁺ release

A positive‑feedback mechanism in which an initial influx of Ca²⁺ (via voltage‑gated channels or IP₃ receptors) triggers the ryanodine receptor on the sarcoplasmic reticulum to release a larger intracellular Ca²⁺ store, amplifying the contraction signal.

Ca²⁺‑ATPase

A pump in the sarcoplasmic reticulum membrane that uses ATP to transport Ca²⁺ from the cytosol back into the SR, lowering intracellular Ca²⁺ concentration and promoting muscle relaxation.

cAMP

A second messenger that activates β‑adrenergic receptors. In smooth muscle, elevating cAMP to bind to protein kinase A (PKA). PKA reduces phosphorylation of target proteins (MLCK), further reducing phosphorylation of MLC and causes smooth muscle contraction

Calmodulin

A protein that binds to Ca²⁺ activates myosin light‑chain kinase (MLCK) in smooth muscle, enabling phosphorylation of the myosin light chain and initiating contraction.

Cardiac muscle

The involuntary, striated muscle that forms the walls of the heart and is responsible for pumping blood throughout the circulatory system.

• Structure: Branched, uninucleated cells linked by gap junctions (for rapid electrical spread) and desmosomes (for strong mechanical attachment). Sarcomeres are present, giving the tissue its characteristic striations.

• Function: Generates spontaneous, rhythmic contractions (automaticity) that are modulated by the autonomic nervous system; each contraction is synchronized across the myocardium due to the electromechanical junctions.

contraction

the process by which muscle fibers generate force and shorten (or develop tension) in response to an electrical or chemical stimulus.

Cross‑bridges (low/high force)

Interactions between myosin heads and actin. Low‑force cross‑bridges attach briefly with limited power‑stroke displacement; high‑force cross‑bridges achieve full attachment and generate maximal tension per cycle.

Dense bodies

Cytoplasmic anchoring sites in smooth muscle where actin filaments attach; they transmit force to the extracellular matrix and replace Z‑lines found in striated muscle.

Desmosomes

Mechanical coupling/junctions formed by transmembrane (cadherin) proteins that physically hold cells together in the extracellular space, providing strong tension in tissues to withstand mechanical strain during muscle contraction.

DHP receptor (dihydropyridine receptor)

A voltage‑sensitive Ca²⁺ channel in the T‑tubule membrane of skeletal muscle is mechanically linked to the SR. Mechanical coupling with the ryanodine receptor triggers Ca²⁺ release from the SR when the sarcolemma depolarizes.

Electromechanical junctions

Hybrid structures that combine gap junctions (electrical coupling) and desmosomes (mechanical coupling). They allow rapid spread of depolarization while keeping cells physically linked during force generation.

Excitation‑contraction coupling

The cascade that converts a somatic motor‑neuron action potential to muscle contraction: ACh release → sarcolemma depolarization → DHP receptor activation → ryanodine receptor Ca²⁺ release → troponin‑tropomyosin shift → cross‑bridge cycling.

• skeletal muscle AP travels down the t-tubules and cause Ca²⁺ release into the SR

Fascicles

Bundles of muscle fibers

Fast‑twitch glycolytic fibers

Large‑diameter skeletal‑muscle fibers that rely primarily on anaerobic respiration for ATP. They have low myoglobin and low blood supply. They generate short contractions and quick movements but fatigue rapidly.

Fatigue

A decline in force output caused by accumulation of inorganic phosphate, H⁺, ADP, depletion of phosphocreatine, and impaired Ca²⁺ handling, all of which reduce cross‑bridge efficiency.

Gap junctions

type of electromechanical junction; electrical coupling/junction of muscle cells; rapid and coordinated propagation of electrical impulses and contractile force via flow of ions between cells

• electrical junctions that allow for cell to pass through the pores bertween electrical synapses

H‑zone

Central part of the A‑band where only thick (myosin) filaments are present. It shortens during contraction as thin filaments slide inward, reducing the region of pure myosin.

IP₃ (inositol 1,4,5‑trisphosphate)

A second messenger generated by phospholipase C that binds receptors on the sarcoplasmic reticulum, triggering Ca²⁺ release and initiating smooth‑muscle contraction.

IP₃ receptors

Ca²⁺‑release channels on the smooth‑muscle sarcoplasmic reticulum that open when bound by IP₃, initiating the intracellular Ca²⁺ rise required for contraction.

I‑band

Region of the sarcomere containing only thin (actin) filaments. It shortens during contraction as the overlap with thick filaments increases.

Latent period

The brief interval (≈2–5 ms in skeletal muscle) between the arrival of an action potential and the onset of measurable tension, reflecting the time needed for Ca²⁺ release and cross‑bridge formation.

M‑line

Central line of the sarcomere where myosin tails are anchored by proteins such as myomesin and creatine kinase. Its length remains constant during contraction.

Motor end plate

The specialized region of the skeletal‑muscle sarcolemma packed with ACh receptors, folded to increase surface area, and containing junctional folds that amplify the synaptic signal.

Multi‑unit smooth muscle

Smooth‑muscle cells that act independently, each innervated by its own motor neuron (e.g., iris muscles). Contractions are localized rather than coordinated across a syncytium.

Muscle fiber

A single, multinucleated (skeletal) or uninucleated (cardiac/smooth) cell that contains many myofibrils. Fibers are organized into fascicles, which assemble into whole muscles.

Myofibril

A rod‑like contractile organelle within a muscle fiber composed of repeating sarcomeres arranged end‑to‑end, giving the fiber its striated appearance.

Myofilaments

The thin (actin, tropomyosin, troponin) and thick (myosin) filaments that slide past each other during the cross‑bridge cycle to produce force.

Myoglobin

An oxygen‑binding protein in the sarcoplasm that stores O₂ and facilitates diffusion to mitochondria. High concentrations give slow‑twitch fibers a red color.

Myosin

A motor protein forming the thick filament; each molecule has a head (ATPase & actin‑binding), neck (lever arm), and tail (coiled‑coil for filament assembly). The head generates the power stroke.

Myosin heavy chain (head, neck, tail domains)

The head contains the ATP‑binding site; the neck binds light chains and amplifies movement; the tail dimerizes to create the backbone of the thick filament.

Myosin light chain

Two light chains (essential and regulatory) bound to the myosin neck. In smooth muscle, phosphorylation of the regulatory light chain by MLCK increases myosin ATPase activity.

Myosin light‑chain kinase (MLCK)

A Ca²⁺‑calmodulin‑dependent enzyme that phosphorylates the regulatory light chain of myosin, enabling cross‑bridge formation in smooth muscle.

Myotonia

A disorder of delayed muscle relaxation caused by defective voltage‑gated Cl⁻ channels (e.g., CLC‑1), leading to prolonged depolarization and repetitive firing.

Myasthenia gravis

An autoimmune disease where antibodies target ACh receptors at the neuromuscular junction, reducing end‑plate potential amplitude and producing fatigable weakness.

Na⁺/Ca²⁺ exchanger

A membrane antiporter that moves 3 Na⁺ ions into the cell while exporting 1 Ca²⁺ ion out, using the Na⁺ gradient to lower cytosolic Ca²⁺ and aid relaxation (especially in cardiac and smooth muscle).

Neuromuscular junction

The synapse where a motor‑neuron terminal contacts the skeletal‑muscle sarcolemma. It comprises the axon terminal, synaptic cleft, motor end plate, and terminal Schwann cells, converting neural action potentials into muscle depolarization.

Nebulin

A gigantic actin‑binding protein that runs along the thin filament from the Z‑disk toward the sarcomere center, acting as a molecular ruler that stabilizes filament length.

Phasic smooth muscle

Smooth‑muscle fibers that contract rapidly and transiently (e.g., intestinal peristalsis). They exhibit fast Ca²⁺ transients and higher MLCK activity but fatigue more quickly than tonic muscle.

Plasmapheresis

A therapeutic procedure that removes circulating autoantibodies (such as anti‑ACh‑receptor antibodies) from the blood, temporarily improving symptoms in disorders like myasthenia gravis.

Power stroke

The force‑generating step of the cross‑bridge cycle: after myosin binds actin and releases inorganic phosphate, the myosin head pivots (~10 nm), pulling the thin filament toward the M‑line and converting chemical energy from ATP hydrolysis into mechanical work.

Polio

Poliovirus infection that destroys lower motor neurons, eliminating the neural input required for muscle activation and causing flaccid paralysis.

Relaxation

The process that returns muscle to its resting length: Ca²⁺ re‑uptake into the SR via SERCA, extrusion via the Na⁺/Ca²⁺ exchanger, dephosphorylation of myosin light chains (smooth muscle), and re‑covering of actin sites by troponin‑tropomyosin.

Rigor state

A condition in which myosin heads remain bound to actin because ATP is unavailable to cause detachment. It occurs after intense activity when ATP is depleted.

Rigor mortis

The post‑mortem stiffening of muscle that occurs when ATP production ceases. Without ATP, myosin heads cannot detach from actin, and Ca²⁺ remains high because SERCA pumps fail. The resulting permanent cross‑bridge attachment locks the sarcomere in a contracted state until proteolytic enzymes break down the filaments.

Ryanodine receptor (skeletal and smooth muscle)

A massive Ca²⁺‑release channel located on the sarcoplasmic reticulum (SR).

• Skeletal muscle: Mechanically linked to the DHP (L‑type) receptor; depolarization of the T‑tube pulls the RyR open, releasing Ca²⁺.

• Smooth muscle: Activated by IP₃ or by Ca²⁺‑induced Ca²⁺ release (CICR), allowing a second wave of Ca²⁺ release from the SR.

Sarcolemma

The specialized plasma membrane of a muscle fiber. It contains voltage‑gated Na⁺ channels, DHP receptors, and invaginations called T‑tubules that transmit the action potential deep into the fiber. It also bears the motor end plate in skeletal muscle.

Sarcomere

The fundamental repeating contractile unit of striated muscle, bounded by two Z‑disks. It comprises an A‑band (myosin + actin overlap), I‑band (actin only), H‑zone (myosin only), M‑line, and the Z‑line. Shortening of the sarcomere by sliding filament interaction produces overall muscle contraction.

Sarcoplasm

The cytoplasm of a muscle fiber; it houses myofibrils, mitochondria, glycogen granules, and myoglobin. This environment supplies ATP, substrates, and oxygen needed for contraction and relaxation.

Sarcoplasmic reticulum (SR)

A specialized form of endoplasmic reticulum that stores Ca²⁺. Its terminal cisternae form triads (or diads) with T‑tubules, allowing rapid, uniform Ca²⁺ release via ryanodine receptors during excitation‑contraction coupling, and rapid re‑uptake via Ca²⁺‑ATPase (SERCA) during relaxation.

Single‑unit smooth muscle

Smooth‑muscle cells that are electrically coupled by abundant gap junctions, functioning as a functional syncytium. A single depolarizing event spreads throughout the tissue, producing coordinated contraction (e.g., intestinal wall).

Skeletal muscle

Voluntary muscle composed of multinucleated, cylindrical fibers with striated sarcomeres. Fibers are organized into fascicles, which are bundled into the whole muscle and attach to bone via tendons. Activation occurs at the neuromuscular junction via somatic motor neurons.

Sliding filament theory

The mechanistic model stating that thin (actin) filaments slide past thick (myosin) filaments during contraction. Filament lengths remain constant; the overlap increases, shortening the sarcomere and generating force. The process is driven by the cross‑bridge cycle and powered by ATP hydrolysis.

Slow‑twitch oxidative fibers (type I)

Small‑diameter, high‑myoglobin, rich‑in‑mitochondria fibers that rely on aerobic metabolism. They produce low force but are highly fatigue‑resistant, making them ideal for posture and endurance activities.

Smooth muscle

Involuntary, unstriated muscle composed of spindle‑shaped, uninucleated cells. Contraction is regulated by calmodulin‑activated MLCK and can be single‑unit (electrically coupled) or multi‑unit (independent). No sarcomeres; force is transmitted via dense bodies and desmosomes.

Striations

The alternating dark (A‑band) and light (I‑band) bands seen in skeletal and cardiac muscle under a microscope. They arise from the regular, repeating arrangement of sarcomeres; smooth muscle lacks this ordered pattern and therefore appears non‑striated.

Summation

The process by which individual twitches combine to produce greater force.

• Temporal summation: High‑frequency stimuli on the same motor unit cause twitches to fuse.

• Spatial summation: Recruitment of additional motor units increases overall tension.

Tendons

Dense, collagen‑rich connective tissue (type I collagen, virtually no elastin) that links muscle fibers to bone. Their stiffness ensures efficient transmission of contractile force without energy‑absorbing stretch.

Terminal cisternae

Enlarged ends of the sarcoplasmic reticulum that flank each T‑tube, forming the triad in skeletal muscle. They store high concentrations of Ca²⁺ and release it rapidly when the adjacent DHP receptor is activated.

Tetanus (muscular)

A sustained, maximal contraction produced when stimuli arrive faster than the muscle can relax, causing complete temporal summation of twitches. It reflects the muscle’s ability to maintain force under high‑frequency neural firing.

Thick filament

Made up of myosin molecules arranged with their heads projecting outward. Each myosin has a head (ATPase & actin‑binding), neck (lever arm), and tail (coiled‑coil). The filament provides the force‑generating heads for the cross‑bridge cycle.

Thin filament

Consists of F‑actin with associated tropomyosin and the troponin complex. In smooth muscle, calmodulin replaces troponin. The filament supplies the binding sites for myosin heads and is regulated by Ca²⁺‑dependent conformational changes.

Titin

A gigantic elastic protein that spans from the Z‑disk to the M‑line within the thick filament. It anchors myosin, provides passive elasticity, and helps center thick filaments, contributing to the muscle’s recoil after stretch.

Tonic smooth muscle

Smooth‑muscle type that maintains sustained, low‑level contraction (e.g., vascular smooth muscle). It exhibits slow cross‑bridge cycling and high Ca²⁺ sensitivity, allowing long‑duration tone with minimal ATP consumption.

Transverse tubules (T‑tubules)

Invaginations of the sarcolemma that run perpendicular to the fiber axis, delivering the action potential deep into the interior of the muscle cell. In skeletal muscle they align with terminal cisternae to form triads; in cardiac muscle they form diads.

Tropomyosin

A rod‑like dimer that winds along the groove of the actin filament, blocking myosin‑binding sites at rest. When Ca²⁺ binds troponin (or calmodulin in smooth muscle), tropomyosin shifts, exposing the sites for cross‑bridge formation.

Troponin

A three‑subunit complex on the thin filament:

• TnC binds Ca²⁺,

• TnI inhibits actin‑myosin interaction, and

• TnT anchors the complex to tropomyosin.
  Ca²⁺ binding induces a conformational change that moves tropomyosin and permits contraction.

Varicosities

Swellings along autonomic nerve fibers that store and release neurotransmitters (e.g., NE, ACh) onto multiple nearby smooth‑muscle cells, facilitating widespread signaling.

Z‑disks (Z lines)

Electron‑dense transverse plaques that mark the boundaries of each sarcomere. They anchor the plus ends of thin filaments and bind nebularin, α‑actinin, and desmin, maintaining alignment of adjacent sarcomeres. During contraction the Z‑disks move toward each other, shortening the sarcomere.

Tonic smooth muscle

Muscle that maintains a sustained, low‑level contraction (high basal tone) to keep sphincters closed or vessels constricted; relies heavily on continuous MLC phosphorylation.