Muscle Physiology Notes

Overview of Muscle Tissue

• Muscle tissue is essential for virtually every body action, serving as the ‘tissue of motility’.
  • Voluntary external movements like walking and speaking.
  • Involuntary internal movements such as blood circulation and GI motility.
• Not all multicellular organisms require muscle or nervous tissue (e.g., plants), but human life depends on muscle tissue for internal physiological processes and dynamic interactions with the environment.

Muscle Biomechanics

• Muscle cells, often called muscle fibers, are large, elongated, electrically excitable cells specialized to contract upon stimulation.
  • Contractility is the defining feature of muscle tissue, often involving shortening along the longitudinal axis.
  • Contraction produces an active, energy-requiring pulling force called tension, applied to an object known as the load.
• To move the load, tension must overcome the passive force of resistance, resulting from weight and friction.
  • If tension exceeds resistance, movement occurs towards the tension source (insertion moves toward the origin).
  • Compression, movement away from the force source, cannot be produced by single muscle fibers but occurs in the body due to whole muscle anatomy, specific attachments, and types of joints.

Muscle Tissue Mechanics

• Muscle cells are bound by connective tissue (CT) fibers, attaching muscles to their origin and insertion.
  • Collagen fibers resist high tensile forces but not compression, effectively transferring muscle tension to the load.
  • Specific motion depends on the arrangement of muscle cells and CT attachments.
  • Elastic fibers interwoven with collagen provide resiliency.
• Understanding muscle mechanics requires considering CT components with passive elastic properties, akin to springs.
  • Parallel elastic components (PECs): CT components (epimysium, perimysium, endomysium) between muscle cells.
  • Series elastic components (SECs): Tendons, sarcomere proteins (Z-discs, titin).
  • These components work with active contractile components (myofilaments) that produce tension.

Functional Characteristics of Muscle Tissue

• Excitability: Ability to initiate and propagate an electrical impulse on the plasma membrane, enabling rapid functional response.
• Contractility: Ability to produce an active pulling force (tension), often involving muscle shortening.
• Extensibility: Ability to stretch beyond resting length, involving elastic CT.
• Elasticity: Ability to return to resting length after change (shortening or lengthening), involving elastic CT.

Contractile Proteins

• Primary proteins of muscle contraction are actin and myosin; ancient and found in all eukaryotic cells.
  • Actin is the major component of microfilaments in the cytoskeleton.
  • Myosin is a motor protein converting ATP’s chemical energy into mechanical energy.
• Actin-myosin interactions are involved in:
  • Internal cellular motility events.
  • Controlled alterations of cell shape.
  • Muscle cells are actin-myosin specialists.

Types of Muscle Tissue

• Muscle tissue exhibits structural and functional heterogeneity across different animal groups.
  • Wide diversity exists (e.g., hummingbird flight muscle vs. bivalve mollusc adductor muscle).
• Vertebrate classes:
  • Skeletal: striated, voluntary control, attached to the skeleton.
  • Cardiac: striated, involuntary, found in the heart myocardium.
  • Smooth (visceral): unstriated, involuntary, arranged in sheets/layers in walls of hollow visceral organs (excluding the heart).
• Even in the human body, subtypes of skeletal and smooth muscle exist, permitting different functional characteristics in terms of power, speed, and endurance.

Nervous Control of Muscle

• Skeletal muscle fibers are innervated and controlled by somatic nerve fibers (somatic nervous system).
  • Skeletal muscle fibers cannot contract without an extrinsic signal from the nervous system.
  • The pattern of nerve stimulation determines the output of skeletal muscle.
  • Skeletal muscle is subject to voluntary control (usually conscious awareness of actions).
• Cardiac and most smooth muscle are innervated by visceral nerve fibers (autonomic nervous system).
  • Autonomic input often modifies ongoing autonomous (myogenic) contractile activity and is part of visceral reflexes.
  • Cardiac and smooth muscle are not subject to voluntary control (usually no conscious awareness).

Skeletal Muscle Tissue

• Skeletal muscle is the major tissue component of skeletal muscles, complex effector organs including CT elements, nerves, and blood vessels.
• Skeletal muscles attach directly or indirectly to bones/cartilages of the skeleton, with functional output dependent on CT organization and nerve stimulation pattern.
• Skeletal muscle is highly specialized with precise cytoarchitecture (biological crystal), built for speed and power.

Skeletal Muscle Functions

• Production of skeletal movement: Lever systems permit a wide variety of motions.
• Maintenance of posture and body position: Muscle tone stabilizes major body joints.
• Support and protection of tissues and organs: e.g., abdominal wall, pelvic floor.
• Guarding entrances and exits of body passageways or openings: Sphincters.
• Thermoregulation: Production of heat warms the body and maintains body temperature.

Connective Tissue Structure of Skeletal Muscle

• Three interwoven connective tissue layers:
  • Epimysium: Surrounds the muscle; dense collagen fibers, some elastic fibers.
  • Perimysium: Inward extensions that define groups of muscle fibers (fascicles); blood vessels and nerve fibers travel within to supply each fascicle.
  • Endomysium: Surrounds each fiber; loose CT that houses a rich capillary network, somatic nerve fibers, and myosatellite cells.

Skeletal Muscle Anatomy

• Visceral striated muscle is identical but associated with soft tissues (diaphragm, pharynx, tongue) rather than skeletal elements.

Connective Tissue Structure

• All three layers (epimysium, perimysium, endomysium) are interwoven, forming a continuous collagen fiber network.
• Epimysium collagen fibers continue externally as tendons or aponeuroses.
  • Tendons: Connect muscle to bone.
  • Aponeuroses: Flattened, tendinous structures interconnecting broad muscles (e.g., galea aponeurotica, abdominal aponeurosis, palmar aponeurosis).

Skeletal Muscle Hierarchy

• Muscle → Fascicle → Muscle Fiber → Myofibril → Myofilament.
• Skeletal muscles are separated by planes of fibrous connective tissue called deep fascia, creating compartmentalization.
  • Compartment syndrome: Excess fluid causes swelling within inelastic compartments, leading to ischemia, neuropathy, and muscle necrosis (indicated by myoglobinuria). See Table 9.1.

Vascular and Nerve Supply

• Muscle contraction requires a lot of energy.
  • CT layers contain a rich vascular network delivering abundant oxygen and nutrients.
  • Fibers contract only in response to signals from nerve fibers of the somatic nervous system, subject to voluntary control.
  • Nerves accompany and parallel the branching of blood vessels in the epimysium and perimysium.
  • In the endomysium, extensive capillary network and nerve fibers supply individual muscle fibers.

Muscle Vascularization

• Muscle capillaries branch and form coiled networks, specialized to accommodate muscle contraction forces.

Skeletal Muscle Innervation

• Neuromuscular synapse: The point of contact between a motor neuron and a skeletal muscle fiber.

Intramuscular (IM) Injections

• IM injections often administer drugs because skeletal muscles are highly vascularized, allowing faster uptake and less tissue irritation compared to subcutaneous or intradermal injections.
• Potential risk of piercing a vessel or nerve (e.g., sciatic nerve underlies gluteus maximus).
• Large muscles with few vessels or nerves are preferred: gluteus medius, vastus lateralis, deltoid.
• Vastus lateralis is preferred in children (development) and elderly (due to atrophy).

Skeletal Muscle Fibers

• Dramatically different from a ‘typical cell’, highly specialized in both structure and function.
• Very large size (~100 μm in diameter, centimeters in length).
• Multinucleate: Multiple gene copies direct synthesis of enzymes and structural proteins.
• Form during development by fusion of many embryonic mesodermal cells called myoblasts, creating a structural syncytium (a.k.a. coenocyte).

Myoblast Fusion

• Embryonic mesoderm cells undergo cell division (to increase number) and enlarge.
• Several myoblasts fuse together to form a myotube.
• Myotube matures into a multinucleate skeletal muscle fiber.

Myosatellite Cells

• A small number of myoblasts do not fuse during development, remaining quiescent within adult skeletal muscles as myosatellite cells.
• Adult mesenchymal cells located within the endomysium just deep to the sarcolemma.
• Upon activation, they permit limited repair and regeneration of skeletal muscle tissue.

The Sarcolemma

• The plasma membrane of the muscle fiber, enclosing the sarcoplasm (cytoplasm) of the cell.
• An electrically excitable membrane that initiates and propagates electrical impulses called action potentials for rapid contraction.
• This surface electrical signal must be rapidly delivered to internal contractile machinery via repeated periodic invaginations of the sarcolemma called transverse tubules (T-tubules).
• T-tubules relay the action potential into the interior of the muscle fiber.

Transverse Tubules

• Sarcolemma, sarcoplasmic reticulum, terminal cisternae, T-tubule, and triad are key components.

Myofibrils

• Specialized cylindrical rod-like organelles unique to striated muscle fibers, housed within the sarcoplasm.
• Occupy ~80% of the internal volume of a skeletal muscle fiber.
• The contractile machinery of the fiber, numbering hundreds to thousands in a single muscle fiber.
• Each extends the entire length of the fiber (~1-2 μm in diameter) with visible striations.

Myofibrils Structure and Composition

• Each myofibril is encircled periodically by inwardly projecting T-tubules.
• Adjacent myofibrils are firmly bound by strong desmin filaments (intermediate filament type).
  • Hold myofibrils in perfect register (striations) so the entire muscle fiber is striated.
  • The desmin filament network also links to the overlying sarcolemma, integrating with external CT elements for mechanical linkage.

Myofibrils and Sarcoplasm

• Located in the sarcoplasm between myofibrils are variable numbers of:
  • Mitochondria: For abundant ATP production.
  • Glycosomes: Granules of the glucose polymer glycogen that serve as internal energy reserves.
  • Myoglobin molecules: Oxygen-binding respiratory pigment for internal oxygen reserves.

Sarcoplasmic Reticulum (SR)

• A highly specialized endoplasmic reticulum within the skeletal muscle fiber, forming a tubular network ‘sleeve’ around each myofibril.
• Functions in the storage and controlled release of calcium ions.
• The SR membrane contains calcium pumps that continually remove free Ca^{++} from the sarcoplasm, maintaining a low concentration (~0.0000001M or 100 nM).
• The level in the SR lumen is 1000X higher than in the sarcoplasm; it also contains calcium-binding storage proteins (calbindin; calsequestrin).
• Including both free and bound Ca^{++}, the SR-sarcoplasm calcium gradient is ~40,000:1.

SR Organization

• Inwardly projecting T-tubules periodically encircle each myofibril.
• On either side of a T-tubule, the SR forms large flanking expansions called terminal cisternae.
• The three structures (two terminal cisternae and a T-tubule) are collectively called a triad.
• Triad membranes are closely linked by membrane proteins, but fluid contents remain separate and distinct.

Myofibril Structure: Sarcomeres

• Myofibrils are composed of smaller myofilaments, structurally classified as thick and thin types.
• These are organized into precise repeating units referred to as sarcomeres.
• A typical myofibril consists of ~10,000 identical sarcomeres placed end-to-end, like the boxcars of a long train.

Myofibril Structure: Sarcomere Function

• Each sarcomere is ~1.6—2.6 μm long and serves as the structural-functional unit of all forms of striated muscle.
• Direct physical interactions occur between thick and thin myofilaments, providing the source of all active tension during muscle contraction.
• The sarcomere also contains hundreds of regulatory and stabilizing proteins.

Striations in Muscle

• Myofibrils have clearly visible striations (light and dark bands) due to differences in the size, density, and distribution of myofilaments in the sarcomeres.
• These striations reflect the precise organization and alignment of the myofilaments into sarcomeres, resulting in a striated (banded) appearance.

Sarcomere Organization

• Thick myofilaments are located at the center, defining the width of the A-band, with the M-line at the midline.
• The A-band contains overlapping thin filaments, forming zones of overlap; triads are strategically positioned here.
• The central area with no overlap is the H-zone.
• The I-band extends from the A-band to the Z-disc (each is actually ½ I-band in a given sarcomere), to which the thin filaments are tightly attached.

Sarcomere Stabilizing Proteins

• Myomesin at M-line anchors thick myofilaments.
• Connectins at Z-disc anchor thin myofilaments.
• Elastic filaments, composed of the protein titin, extend from the tips of thick myofilaments to attachment sites at Z-disc, maintaining the proper alignment of thin and thick myofilaments.
• These resist extreme stretching and provide resiliency, helping the sarcomere return to its resting length after contraction.

Sarcomere Cross-Sections

• Illustrate the arrangement of myosin and actin filaments in different regions: I band (thin filaments only), H zone (thick filaments only), M line (thick filaments linked by accessory proteins), and outer edge of A band (thick and thin filaments overlap).

Muscular Dystrophies

• Hereditary myopathies involve progressive striated muscle tissue deterioration, often X-linked recessive traits.
• Result in the degeneration of skeletal and cardiac striated muscle fibers, often leading to death from heart/lung failure.
• Many forms involve an absence or defect of proteins in the costameres, linking sarcomeres of outermost myofibrils to sarcolemma and ECM.

Duchenne Muscular Dystrophy

• An X-linked hereditary myopathy typically occurring in young males ages 3-7 (Gower’s sign).
• Due to a mutated gene on the X chromosome, coding for the costamere protein dystrophin, linking actin of outermost sarcomeres to the rest of the costamere complex.
• Absence leads to progressive muscle fiber degeneration and weakness.

Thin Filament Structure

• Consists of two intertwined strands of F-actin (~5-6 nm in diameter, ~1 μm in length), forming a twisted double strand.
• F-actin strand = 300-400 subunits of G-actin, each with a myosin binding site.
• Associated with the thin filament are tropomyosin and troponin, regulatory proteins.

Thin Filament Regulation

• In the resting state, tropomyosin strands cover the binding sites on the G-actin subunits, sterically blocking physical interaction of actin with myosin heads.
• Troponin is a trimer (subunits TnT, TnI, and TnC) that regulates the position of tropomyosin.
• Isoforms of TnT and TnI in cardiac muscle serve as key blood indicators of myocardial damage.

Thick Filament Structure

• Consists of ~500 bundled molecules of myosin II (~10-12 nm in diameter, ~1.6 μm in length).
• The myosin II molecule is a dimer (paired polypeptide subunits twisted about each other), each subunit having a heavy chain and light chain.
• A stiff rod-like tail is oriented toward the M-line; a flexible hinge-like neck; and a globular head.
• The head contains an actin-binding site and an enzymatic ATPase site that hydrolyzes ATP, extending laterally to interact with thin filaments.

Myofilament Arrangement

• In the center of the sarcomere, the thick filaments lack myosin heads. Myosin heads are present only in areas of myosin-actin overlap.

Contraction Events

• Involve direct physical interactions between myosin heads and actin subunits in a sarcomere, forming cross-bridges.
• The myosin head repeatedly binds to the actin, ratchets forward on the neck, releases, and repeats.
• The series of events = the cross-bridge cycle, converting chemical energy (ATP) to mechanical energy (active tension) and heat.
• Thin filaments are pulled past the thick filaments (Sliding filament model of muscle contraction).

The Cross-Bridge Cycle

1. Myosin cross-bridge attaches to the actin myofilament.
2. Working stroke: The myosin head pivots and bends as it pulls on the actin filament, sliding it toward the M line.
3. As new ATP attaches to the myosin head, the cross-bridge detaches.
4. As ATP is split into ADP and Pi, cocking of the myosin head occurs.

Contraction Cycle

1. Begins with electrical events in the sarcolemma that trigger the release of calcium from the terminal cisternae of the sarcoplasmic reticulum (SR).
2. Calcium ions bind to troponin in the troponin–tropomyosin complex.
3. The tropomyosin molecule then rolls away from the active sites on the actin molecules of the thin filaments.
4. Once the active sites are exposed, the myosin heads of adjacent thick filaments bind to them, forming cross-bridges.
5. After cross-bridge formation, energy is released as the myosin heads pivot toward the M line.
6. ATP then binds to the myosin heads, breaking the cross-bridges between the myosin heads and the actin molecules.
7. ATP provides the energy to reactivate the myosin heads and return them to their original positions.

Sliding Filament Model

• A resting sarcomere showing the locations of the I band, A band, H band, M line, and Z lines.
• After repeated cycles of “bind, pivot, detach, and reactivate” the entire muscle completes its contraction.
• In a contracting sarcomere, the A band stays the same width, but the Z lines move closer together, and the H band and the I bands get smaller.
  • I-bands shorten/disappear, H-zone disappears, Z-discs move closer, A-band is unchanged.

Rigor Mortis

• A rigid state of skeletal muscle during the immediate post-mortem period.
• Occurs because ATP binding is required for the detachment of the myosin heads.
• In the absence of ATP, the cross-bridges stay locked in place, and the muscles are stiff.
• Rigor begins to appear several hours after death.
• Eventually (12-36 hours post-mortem), it diminishes as the decay process begins.

The Neuromuscular Junction (NMJ)

• The specialized communicating connection between a neuron and a target cell is a synapse.
• A skeletal muscle fiber is controlled by a somatic motor neuron at a single site of contact (the NMJ) located midway along the fiber.
• A single somatic motor axon branches within the perimysium to form a number of axon collaterals, each contacting a different muscle fiber via terminal branches (telodendria).
• Ends in expanded swellings (axon terminals).

Axon Terminals

• Axonal structures that contact the muscle fiber, also called synaptic end bulbs or boutons.
• An axon terminal houses a large number of membranous synaptic vesicles arranged in rows and bound to the axon terminal membrane by docking proteins.
• Each contains many molecules of the chemical neurotransmitter acetylcholine (ACh).
• A neurotransmitter is defined as ‘a chemical released by a neuron at a synapse that alters the membrane properties of the post-synaptic cell’.

Synaptic Cleft

• A narrow space of ~20 nm separates the axon terminal from the underlying sarcolemma; this space is the synaptic cleft.
• The enzyme acetylcholinesterase (AChE) is bound to the basement membrane at the cleft, acting to rapidly degrade ACh after release.

Motor End Plate

• The specialized sarcolemma region underlying the axon terminal is the motor end plate.
• It is characterized by deep creases called junctional folds, which amplify receptive surface area.
• Each fold houses many acetylcholine receptors (AChRs), transmembrane proteins that bind ACh and function as ligand-gated cation channels.

The Action Potential

• A unique cellular electrical signaling event that occurs on the membrane of excitable cells (primarily neurons and muscle fibers).
• Involves a sequence of electrical changes—first depolarization, followed by repolarization.
• Once initiated, it progresses (propagates) rapidly along the excitable membrane.

Action Potential Event

• Electrical conditions of a resting (polarized) sarcolemma: The outside face is positive, while the inside face is negative. The predominant extracellular ion is sodium (Na+); the predominant intracellular ion is potassium (K*).
• The sarcolemma is relatively impermeable to both ions.
• Step 1: Depolarization and generation of the action potential.
• Step 2: Propagation of the action potential.
• Step 3: Repolarization.

Events of Neurotransmission

1. Arrival of an action potential at axon terminal.
2. Depolarization of the axon terminal membrane.
3. Triggers opening of voltage-gated Ca^{++} channels.
4. Influx of ionic Ca^{++} into the axon terminal.
5. Ca^{++} triggers the exocytosis of synaptic vesicles.
6. ACh is released and diffuses across the synaptic cleft.
7. ACh binds to ACh receptors on junctional folds; triggers opening of ligand-gated cation channels.
8. Permits inward ionic (Na+ and Ca^{++}) current.
9. Membrane depolarization (end-plate potential) triggers an action potential on the sarcolemma.

End-Plate Potential (EPP)

• An end-plate potential is generated at the neuromuscular junction.

Sarcolemma Action Potential

1. Local depolarization: generation of the end plate potential on the sarcolemma.
2. Depolarization: Generating and propagating an action potential (AP).

Termination of NMJ Signaling

• AChE in the synaptic cleft rapidly hydrolyzes the ACh into acetate and choline.
• Acetate and Choline are taken back up into the axon terminal and glial cells by membrane transporters.
• In the axon terminal, ACh is resynthesized and repackaged into new synaptic vesicles.
• Myasthenia gravis: An autoimmune disorder where autoantibodies and lymphocytes target and destroy AChRs, resulting in muscle weakness and paralysis.

Excitation-Contraction Coupling (EC Coupling)

• Events linking action potential (external signal) to SR release of ionic calcium (internal signal).
• The action potential moves along the sarcolemma and each T-tubule, depolarizing the T-tubule membrane.
• Voltage sensor proteins are located in the membrane of T-tubules at the triad regions, coupled to mechanically-gated calcium- channels in the terminal cisternae membrane.
• Depolarization causes voltage-sensor to rotate, pulling open mechanically-gated Ca^{++} channels.
• Ca^{++} enters the sarcoplasm (right at the zone of overlap).

EC Coupling Events

1. Action potential is propagated along the sarcolemma and down the T tubules.
2. Voltage-sensitive tubule proteins control calcium release channels open and Ca 2+ enters.

EC Coupling and Calcium

• Calcium is the internal signal for cross-bridge formation.
• Ca^{++} flows out of the terminal cisternae, increasing the concentration in the sarcoplasm.
• Ca^{++} binds to the TnC subunit of the troponin complex on the thin myofilaments.
• A conformational change moves tropomyosin, pulling it deeper into the groove of the thin myofilament, away from the actin binding sites.
• Allows actin interaction with myosin heads, and the cross-bridge cycle begins, producing active muscle tension.

Termination of Contraction

• SR permeability changes are very brief, with Ca^{++} channels closing and Ca^{++}-ATPase pumps in SR membrane rapidly reclaiming the released Ca^{++}.
• Troponin is restored to its resting conformation, and tropomyosin slides back over the actin binding site.
• No more cross-bridges or tension production.
• If shortened, passive return to resting length is achieved by elastic recoil (titin and elastic CT), gravity, or opposing muscle contraction.

Summary of Muscle Contraction Events

1. Neurotransmitter released diffuses across the synaptic cleft and attaches to ACh receptors on the sarcolemma
2. Action potential generated is propagated along the sarcolemma and down the T tubules
3. Action potential triggers Ca^{2+} release from terminal cisternae of SR
4. Calcium ions bind to troponin
5. Tropomyosin blockage restored, blocking actin active site
6. Contraction ends, and muscle fiber relaxes
7. Removal of Ca^{2+} by active transport into the SR after the action potential ends

Steps in Initiation and Relaxation

Initiating:

1. ACh released, binding to receptors
2. Action potential reaches T tubule
3. Sarcoplasmic reticulum releases Ca2+
4. Active-site exposure, cross-bridge formation
5. Contraction begins

Relaxation:

6. ACh removed by AChE
7. Sarcoplasmic reticulum recaptures Ca2+
8. Active sites covered, no cross-bridge interaction
9. Contraction ends
10. Relaxation occurs, passive return to resting length

NMJ and Excitation-Contraction Summary

1. Action potential (AP) arrives at axon terminal at the neuromuscular junction.
2. ACh released; binds to receptors on sarcolemma.
3. Ion permeability of sarcolemma changes.
4. Local change in membrane voltage (depolarization) occurs.
5. Local depolarization (end plate potential) ignites AP in sarcolemma.
6. AP travels across the entire sarcolemma and along T tubules.
7. SR releases Ca^{2+}; Ca^{²+} binds to troponin; myosin-binding sites (active sites) on actin exposed.
8. Myosin heads bind to actin; contraction begins.

Disruption of NMJ Signaling

• Organophosphate chemicals act as irreversible inhibitors of AChE (covalent modifiers).
  • Nerve agents (e.g., Sarin).
  • Pesticides (e.g., malathion, parathion).
• Flaccid paralysis and death from asphyxiation.
• Temporary and reversible flaccid paralysis can be induced by acetylcholine analog compounds (surgical paralytics) such as succinylcholine to prevent muscular contractions during surgery.

NMJ Signaling - Poisons and Toxins

• Many natural poisons and toxins interfere with signaling at the skeletal neuromuscular junction.
• Curare, a plant alkaloid used as an arrowhead poison, is an antagonist of nicotinic ACh receptors, preventing EPP and contraction, leading to death by asphyxiation.
• Botulinum toxin prevents the release of Ach (Botox treatment).

Passive and Active Tension

• Muscle fibers exhibit passive elastic properties; passive tension increases with stretch due to titin filaments and connective tissue series-elastic elements.
• The stretched fiber returns to its resting length by elastic recoil if released.
• The length at which a contracting muscle fiber develops maximal active tension is termed the optimal length (L_0).

Length-Tension Relationship

• The amount of active tension produced is directly proportional to the number of cross-bridges reflecting the extent of myofilament overlap.
• The degree of myofilament overlap in striated muscle is very sensitive to resting length due to precise sarcomere organization.
• If the sarcomere is stretched or compressed, cross-bridge formation and tension fall sharply.
  The degree of myofilament overlap in striated muscle is very sensitive to resting length due to precise sarcomere organization.
• The operating range in which tension can be best produced is ~80%-120% of resting fiber length.

Length-Tension and Sarcomeres

• Sarcomeres in skeletal muscle are usually kept within their optimal operating range by titin and the attachments of skeletal muscles.
• Muscles typically contract over a wide range of intermediate lengths; tension produced varies.
• Muscles work as groups; the muscle fibers are stretched to optimal length before contracting when compared with L/T relationship of cardiac muscle.
• Muscles are structurally specialized for specific functions.

Skeletal Muscle Mechanics

• The amount of tension produced by the muscle fiber depends on the number of cross-bridges (length).
• A given length always results in the same tension.
• There is no mechanism to adjust the tension by regulating sarcomere contraction in a fiber.
• A single muscle fiber is either ON or OFF (the all-or-none principle).
• In contrast, whole skeletal muscles contain many individual muscle fibers, structurally and functionally independent.

Control of Whole Muscles

• Individual fibers can be controlled separately, allowing whole muscles to produce graded levels of tension, unlike a single muscle fiber.
• A whole muscle is supplied by a motor nerve composed of many nerve fibers or axons (somatic motor neurons, cell bodies in CNS).
• Axons form collaterals (branches) in the perimysium, each contacting one muscle fiber (NMJ).
• Each neuron, therefore, controls a certain number of muscle fibers in a given muscle, and each fiber is innervated by only one neuron.

The Motor Unit

• A motor unit is defined as: A somatic motor neuron and all the muscle fibers that it controls in that muscle.
• The size of motor units varies widely from one muscle to another or even within a given muscle, directly related to the required level of motor control and precision.
• In a given muscle, the muscle fibers of an individual motor unit are evenly distributed, so activation of different motor units does not alter the resulting tension vector.

Skeletal Muscle Contraction

• The physiological meaning of contraction refers to the activation of cross-bridges.
• It does NOT mean that the muscle NECESSARILY shortens in length.
• In some contractions, the muscle may shorten; in other contractions, it may stay the same length or lengthen.
• Holding a weight at a constant position requires muscle contraction, but not muscle shortening (an isometric contraction).

Simple Contractions and Load

• A muscle functions as a biological electromechanical force transducer, generating an active force called tension that opposes a passive resistance force called the load (weight, friction, etc.).
• Fundamentally, if the tension exceeds the load, movement occurs.

The Muscle Twitch

• Mechanical response of a muscle fiber (or whole muscle) to a single stimulus is a muscle twitch: ‘A single stimulus-contraction-relaxation sequence in an isolated whole muscle’.
• A graphic tracing of twitch contractile activity displaying tension vs. time is a myogram.

Phases of Muscle Twitch

• The twitch event consists of three phases:
  • Latent phase (period): The time from the action potential to the onset of contraction (slight delay due to excitation-contraction coupling events).
  • Contraction phase: The time that active tension is developing due to cross-bridge cycling.
  • Relaxation phase: The time that the tension is decreasing (muscle is relaxing, longer than contraction phase due to time required to sequester Ca^{2+}).

Twitch Times & Muscle Work

• Twitch times vary in different muscle fibers due to metabolic and enzymatic differences (fast-twitch vs. slow-twitch).
• Isolated muscle twitches cannot perform useful work, actions that do work involve sustained contractions and graded levels of tension, characterizing normal body motions.
• Single twitch events do not typically occur in healthy skeletal muscles.

Mechanisms of Control

• Sustained contractions and graded tension levels are produced by varying neural stimulation.
  • Varying the frequency of stimulation.
  • Varying the strength of stimulation.
• Increased tension within a skeletal muscle due to changed stimulation is called summation.
  • Temporal (wave) summation is due to increased stimulation frequency.
  • Spatial summation is due to increased stimulation strength.

Treppe

• If a skeletal muscle is stimulated a second time immediately after the relaxation phase has ended, the resulting contraction will develop a slightly higher maximum tension than the first.
• The increase continues over the first 30-50 stimulations; tension then remains constant at ~25% of a maximal tetanic contraction.
• This phenomenon is called treppe.
• It may be due to a warming effect in the muscle as well as the increased availability of calcium ions.

Temporal (Wave) Summation

• Wave summation occurs when a second stimulus arrives before the relaxation phase of the first stimulus is over.
• The tension remaining from the first twitch event is added to that of the second, leading to a stronger contraction.
• The tension begins to increase (summate) illustrating the frequency-tension relationship.

Muscle Tetanus

• Rapid, repeated stimuli increase tension, eventually reaching a peak value called tetanus (‘a state of maximal, sustained contraction’).

• Peak tension in rapid cycles of contraction and relaxation is incomplete (unfused) tetanus.

• High-frequency stimulus results in complete (fused) tetanus (no relaxation phase).

• All normal contractions involve fused tetanus.

  • Comparison with cardiac muscle.

• Medical tetanus: due to neurotoxin tetanospasmin in puncture wounds infected by C. tetani.

Basis of Wave Summation

• The mechanism of wave summation is based on the principle that the output time >> signal time.
  • Action potential (signal) ~ 1-2 ms.
  • Muscle twitch (output) ~ 50-100 ms.
• The stimulation frequency necessary to produce wave summation depends on the twitch time.
  • For a twitch time of 100 ms, wave summation occurs if the stimulus frequency is ≥ 10 Hz.
  • For a twitch time of