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Muscle Anatomy and Physiology Notes

Microscopic Anatomy of Skeletal Muscle

  • Skeletal muscle fibers are long, cylindrical cells.

  • Each fiber has multiple oval-shaped nuclei under the sarcolemma (plasma membrane).

  • Diameter: 10-100 micrometers.

  • Length: up to 30 centimeters (due to fusion of embryonic cells).

  • Sarcoplasm: cytoplasm with glycosomes and myoglobin.

  • Organelles: typical cell organelles, myofibrils, sarcoplasmic reticulum (SR), and T-tubules.

Myofibrils

  • Hundreds to thousands per muscle fiber.

  • Run parallel to the muscle fiber.

  • Occupy 80% of cell volume.

  • Contain sarcomeres (responsible for contraction).

  • Sarcomeres contain three types of myofilaments.

Sarcoplasmic Reticulum (SR)

  • Smooth endoplasmic reticulum surrounding myofibrils.

  • Most tubules run along the myofibril's long axis.

  • Terminal cisterns run perpendicularly in pairs.

  • Function: Regulate calcium ion (Ca^{2+}) levels; store and release Ca^{2+} to signal contraction.

T-Tubules

  • Elongated tubes between paired terminal cisterns, forming triads.

  • Triads consist of a T-tubule and two terminal cisterns.

  • T-tubules are extensions of the sarcolemma.

  • Function: Conduct electrical impulses to sarcomeres, triggering Ca^{2+} release.

Sliding Filament Model of Contraction

  • Myosin heads bind to actin, forming cross-bridges.

  • Cross-bridges repeatedly form and break, sliding thin filaments toward the sarcomere's center.

  • Sarcomere shortens as thin filaments slide.

  • Z discs are pulled toward the M line.

  • I bands shorten, Z discs move closer, H zones disappear, A bands move closer.

Myofilaments

  • Thick filaments: Primarily myosin, located in the center.

  • Thin filaments: Primarily actin, located towards the sides; also contain tropomyosin (blocks myosin-binding sites) and troponin (binds to actin, tropomyosin, and Ca^{2+}).

  • Elastic filaments: Composed of titin, a giant protein that holds thick filaments in place.

Proteins in Muscle Contraction

  • Myosin, actin, tropomyosin, troponin, and titin play roles in the cross-bridge cycle.

  • Other proteins: Dystrophin, nebulin, myomesin, and C proteins also contribute.

Physiology of Skeletal Muscle

Neuromuscular Junction

  • Somatic motor neurons activate skeletal muscle fibers.

  • Axons extend to muscle cells and form neuromuscular junctions.

  • Axon terminal is separated from the muscle fiber by the synaptic cleft (filled with gel-like substance).

  • Synaptic vesicles in the axon terminal contain acetylcholine (ACh).

  • Junctional folds on the sarcolemma increase surface area for ACh receptors.

Action Potential and Muscle Contraction

  • Action potential reaches axon terminal, releasing ACh into the synaptic cleft.

  • ACh diffuses across the cleft and binds to ACh receptors on the sarcolemma.

  • Acetylcholinesterase breaks down ACh, preventing continuous contraction.

  • ACh binding opens ligand-gated ion channels, increasing Na^{+} influx and decreasing K^{+} efflux, causing depolarization.

  • Endplate potential (localized depolarization) spreads and opens voltage-gated Na^{+} channels.

  • If threshold potential is reached, an action potential is generated.

  • Depolarization wave opens voltage-gated Na^{+} channels along the sarcolemma.

Repolarization

  • Voltage-gated Na^{+} channels close, and voltage-gated K^{+} channels open.

  • K^{+} efflux causes repolarization.

  • Muscle fibers enter a refractory period until repolarization is complete.

Classification of Skeletal Muscle Fibers

  • Based on contraction velocity: Slow fibers and fast fibers.

  • Based on ATP production pathways: Oxidative fibers and glycolytic fibers.

Slow Oxidative (SO) Fibers
  • Contract slowly due to slow myosin ATPases.

  • Dependent on oxygen delivery and aerobic pathways.

  • High myoglobin (red), low glycogen, small diameter, many mitochondria, many capillaries.

  • Best suited for endurance activities.

Fast Oxidative (FO) Fibers
  • Contract quickly due to fast myosin ATPases.

  • Dependent on aerobic pathways but also use glycolytic reserves.

  • High myoglobin (red to pink), moderate glycogen, moderate diameter, many mitochondria, many capillaries.

  • Best suited for sprinting and walking.

Fast Glycolytic (FG) Fibers
  • Contract rapidly due to fast myosin ATPases.

  • Independent of oxygen; use glycolytic reserves.

  • Low myoglobin (white), low glycogen, large diameter, few mitochondria, few capillaries.

  • Best suited for short, rapid, intense movements.

Muscle Tension and Load

  • Muscle tension: Force exerted by a muscle on an object.

  • Load: Force exerted on the muscle by the weight of the object.

Types of Contractions
  • Isometric: Muscle exerts force, but the load doesn't move; muscle fiber length doesn't change.

  • Isotonic: Muscle force overcomes the load; muscle fiber length changes.

    • Concentric: Muscle shortens.

    • Eccentric: Muscle lengthens.

Muscle Tone

  • Slight contraction even when relaxed.

  • Keeps muscles firm, healthy, and ready to respond.

  • Assists in joint stabilization and posture maintenance.

Metabolism in Muscle

ATP Regeneration

  • Muscles store ATP for only 4-6 seconds of activity.

  • ATP must be regenerated quickly.

  • Three pathways regenerate ATP after hydrolysis to ADP and inorganic phosphate.

Direct Phosphorylation
  • Creatine phosphate (CP) regenerates ATP.

  • CP + ADP → ATP (catalyzed by creatine kinase).

  • Muscles store 2-3 times more CP than ATP; provides ~15 seconds of power.

  • CP is replenished during rest.

Anaerobic Glycolysis
  • Used when ATP and CP are exhausted.

  • ATP generated by catabolizing glucose (from blood or muscle glycogen).

  • Does not require oxygen.

  • Glucose → 2 pyruvic acid molecules.

  • Pyruvic acid converted to lactic acid during rigorous activity.

  • Harvests 5% of ATP compared to aerobic respiration but is 2.5 times faster.

  • Useful for 30-40 seconds of strenuous activity.

Aerobic Respiration
  • Produces 95% of ATP during rest, light exercise, and moderate exercise.

  • Requires oxygen.

  • Glucose + Oxygen → Carbon dioxide + Water + ATP.

  • Glycogen becomes pyruvic acid, then fatty acids are used.

  • Produces a large quantity of ATP but is slow.

Smooth Muscle

Microscopic Anatomy

  • Located in the walls of most hollow organs (except the heart).

  • Spindle-shaped cells with a central nucleus.

  • 1/10th the width and thousands of times shorter than skeletal muscle fibers.

  • Fine connective tissue (endomysium) between cells.

  • Organized into two sheets:

    • Longitudinal layer (outer): Fibers run parallel to the organ's long axis; contraction dilates or shortens the organ.

    • Circular layer (inner): Fibers run around the organ's circumference; contraction constricts or elongates the organ.

  • Peristalsis: Continuous involuntary contraction and relaxation of the two layers, propelling and mixing substances.

Innervation and Excitation-Contraction Coupling

  • Innervated by autonomic (involuntary) nervous system fibers.

  • Nerve fibers have varicosities that form diffuse junctions.

  • Varicosities release neurotransmitters into the synaptic cleft.

  • Less developed sarcoplasmic reticulum compared to skeletal muscles.

  • Lacks T-tubules but has caveolae (pouchlike infoldings) that sequester extracellular Ca^{2+}.

  • Extracellular Ca^{2+} is primarily responsible for excitation-contraction coupling.

Filament Arrangement

  • Not striated; lacks sarcomeres.

  • Myosin to actin ratio is 1:13 (vs. 1:2 in skeletal muscles).

  • Surplus of myosin heads along the entire length of the muscle.

  • Lacks troponin complexes; calmodulin is the Ca^{2+}-binding site.

  • Contracts in a corkscrew-like manner due to diagonal arrangement of filaments.

Physiology

  • Contracts slowly and synchronously due to gap junctions.

  • Pacemaker cells set the pace of contraction.

  • Sliding filament model and ATP utilization apply.

  • Contraction triggered by rises in intracellular Ca^{2+} levels.

  • Ca^{2+} activates myosin by interacting with calmodulin.

  • Calmodulin activates myosin kinase (myosin light chain kinase), which phosphorylates myosin.

  • Contracts 30 times slower than skeletal muscles; maintains tension longer with less energy.

Regulation of Contraction

  • Regulated by neural stimuli, hormones, and localized chemical changes.

  • Neural stimuli generate action potentials and increase cytosolic Ca^{2+} levels.

  • Nerve endings release various neurotransmitters that stimulate different smooth muscle fibers.

  • Receptor molecules (ACh receptors, norepinephrine receptors, etc.) determine which fibers are stimulated.

  • Some smooth muscles contract through spontaneous depolarization or in response to chemical stimuli that bind to G protein-linked receptors.

  • Hormones, histamine, excess CO_2, low pH, and lack of oxygen can cause contraction or relaxation.

Special Features

  • Maintains muscle tone without fatigue.

  • Stretching causes initial contraction followed by adaptation and relaxation.

  • Allows hollow organs to contract and relax slowly without expelling all contents.

  • Smooth muscle stretching generates more tension than skeletal muscle stretching.

  • Smooth muscles can shorten to half their length and lengthen to twice their length, while skeletal muscles can only undergo length changes of 30% to remain functioning.

Hypertrophy and Hyperplasia

  • All muscle fibers can hypertrophy (increase in size).

  • Some smooth muscle fibers undergo hyperplasia (divide and increase in number).

  • Example: Uterus growth during puberty and pregnancy.

Types of Smooth Muscle

Unitary Smooth Muscle
  • Found in the walls of all hollow organs except the heart (visceral muscle).

  • Displays the characteristics listed above.

Multi-Unit Smooth Muscle
  • Found in arrector pili muscles and internal eye muscles.

  • Gap junctions and spontaneous depolarization are rare.

  • More similar to skeletal muscles with independent muscle fibers and neuromuscular junctions.

  • Served by the autonomic nervous system and responds to hormones.

Cardiac Muscle

  • Found only in the walls of the heart.

  • Striated and involuntary.

  • Pacemaker cells set the tempo for contraction.

  • ATP produced via aerobic pathways.

  • Branched cells forming chains.

  • Typically has a single nucleus (may have two during late fetal development).

  • Has endomysium attached to the fibrous skeleton of the heart.

  • Similar sarcoplasmic reticulum to smooth muscles.

  • Ca^{2+} for contraction comes from both the sarcoplasmic reticulum and extracellular fluid.

  • Contraction speed is slower than skeletal but faster than smooth muscles.

  • Has myofibrils like skeletal muscle but with irregular thickness.

  • Gap junctions present at intercalated discs; neuromuscular junctions absent.

  • Troponin complexes present (similar to skeletal muscle).

  • Contains one large T-tubule per sarcomere (rather than two smaller ones).