The Muscular System

• The muscular system is being discussed.

Learning Objectives Covered

• Characteristics of muscle tissue described.
• Functions of skeletal muscle explained.
• Connective tissue layers associated with skeletal muscle identified and described.
• Structures and functions of tendons and aponeuroses described.
• Functions of blood vessels and nerves serving a muscle explained.
• How a skeletal muscle fiber becomes multinucleated explained.
• The sarcolemma, T-tubules, sarcoplasmic reticulum, and triad of a skeletal muscle fiber described.
• Thick and thin filaments distinguished.
• The organization of myofibrils, myofilaments, and sarcomeres explained.
• A motor unit is defined, and the distribution in a muscle and why it varies in size is described.
• The three components of a neuromuscular junction described.
• A skeletal muscle fiber at rest is described.

Characteristics of Muscle Tissue

• Contractility is exhibited when filaments slide past each other, enabling muscle movement.
• Excitability is the ability to respond to a stimulus by changing electrical membrane potential.
• Conductivity involves sending an electrical change down the length of the cell membrane.
• Extensibility is the ability to be stretched.
• Elasticity is the ability to return to original length following a lengthening or shortening.

Functions of Skeletal Muscle Tissue

• Body movement
• Maintenance of posture
• Temperature regulation
• Storage and movement of materials
• Support soft tissue
• Muscle fiber = muscle cell
• Skeletal muscle's fibers are striated and usually attached to bones,
• Muscle fibers are bundled within a fascicle,
• A whole muscle contains many fascicles,
• A fascicle consists of many muscle fibers.

Layers of Connective Tissue Around Muscle Components

• Epimysium is dense irregular connective tissue wrapping the whole muscle.
• Perimysium is dense irregular connective tissue wrapping fascicles, housing many blood vessels and nerves.
• Endomysium is areolar connective tissue wrapping individual fibers, creating a delicate layer for electrical insulation, capillary support, and binding neighboring cells.

Muscle Attachments

• They attach muscle to bone/skin/another muscle.
• A tendon is a cordlike structure of dense regular connective tissue.
• Aponeurosis is a thin, flattened sheet of dense irregular tissue.

Deep Fascia

• It is a dense irregular CT superficial to epimysium.
• Deep fascia separates individual muscles and binds muscles with similar functions.

Superficial Fascia

• It is areolar and adipose CT superficial to deep fascia.
• Superficial fascia separates muscles from skin.
• Origin is the fixed end of the skeletal muscle (bone, cartilage).
• Insertion is the attachment of the movable end of the skeletal muscle to another structure.

Microscopic Anatomy of Skeletal Muscle

• Sarcoplasm (cytoplasm) has typical organelles plus contractile proteins and other specializations.
• Multiple nuclei (individual cells are multinucleated): the cell is formed in the embryo when multiple myoblasts fuse.
• Some nearby myoblasts become undifferentiated satellite cells for support and repair of muscle fibers.

Internal (microscopic) Structure of Skeletal Muscle Fiber

• The sarcolemma (plasma membrane) has T-tubules (transverse tubules) that extend deep into the cell.
• Sarcolemma and its T-tubules have voltage-gated ion channels that allow for conduction of electrical signals.
• T-tubules have voltage-sensitive calcium channels responsive to the electrical signals (action potentials).

Sarcoplasmic Reticulum

• It is an internal membrane complex similar to smooth ER.
• Terminal cisternae are blind sacs of sarcoplasmic reticulum that serve as reservoirs for calcium ions.
• Two cisternae with a T-tubule in between = triad.
• Contains calcium pumps that import calcium and calcium release channels triggered by electrical signal traveling down T-tubule resulting in calcium released into sarcoplasm.

Myofibrils

• Hundreds to thousands per each cell
• Bundles of myofilaments (contractile proteins within muscle)
• Enclosed in sarcoplasmic reticulum
• Thick filaments are bundles of many myosin protein molecules.
• Thin filaments consist of bundles of many myosin protein molecules.
  • Actin with myosin binding sites where myosin heads attach
  • Tropomyosin
  • Troponin

Organization of a Sarcomere (contractile unit)

• Myofilaments are arranged in repeating units called sarcomeres.
• Sarcomeres are composed of overlapping thick and thin filaments.
• Sarcomeres delineated at both ends by Z discs.
• There are specialized proteins perpendicular to myofilaments.
• Anchors for thin filaments
• The positions of thin and thick filaments give rise to alternating I-bands and A-bands.

Banding Pattern of the Sarcomere

• H zone is the central portion of A band.
  • It disappears with maximal muscle contraction
  • Only thick filaments are present
• M line is the middle of H zone.
  • Protein meshwork structure
  • Attachment site for thick filaments
• I band appears light and containins only thin filaments, bisected by the Z disc.
  • Get smaller when muscle contracts
• A band appears dark, containing thick and thin filaments.
  • It contains H zone and M line and makes up central region of sarcomere

Innervation of Skeletal Muscle Fibers

• A motor unit is a motor neuron and all the muscle fibers it controls.
• Axons of motor neurons from spinal cord (or brain) innervate numerous muscle fibers.
• The number of fibers a neuron innervates varies.
• Small motor units have less than five muscle fibers, allowing for precise control of force output.
• Large motor units have thousands of muscle fibers - allowing for production of a large amount of force (but not precise control).
• Fibers of a motor unit are dispersed throughout the muscle.

Neuromuscular Junction

• Is the location where the motor neuron innervates muscle.
• Location is usually the mid-region of the muscle fibre.
• Parts
  • synaptic knob
  • synaptic cleft
  • motor end plate

Synaptic Knob of Motor Neuron

• Expanded tip of the motor neuron axon
• Houses synaptic vesicles, small sacs filled with neurotransmitter acetylcholine (ACh)
• Has Ca2+ pumps in plasma membrane, establishing a calcium gradient, with more outside the neuron.
• Contains voltage-gated Ca2+ channels in membrane, where Ca2+ flows into the cell if channels open

Components of Synaptic Structure

• Synaptic cleft is a narrow fluid-filled space that separates synaptic knob from motor end plate and contains acetylcholinesterase.
• Acetylcholinesterase breaks down ACh molecules.

Motor End plate

• Specialized region of sarcolemma with numerous folds
• Contains many ACh receptors
• Plasma membrane protein channels
• Opened by binding of ACh
• Allow Na+ entry and K+ exit

Skeletal Muscle Fibers at Rest

• Exhibit resting membrane potential (RMP)
• Fluid inside cell is negative compared to fluid outside cell
• RMP of muscle cell is about -90 mV
• RMP established by leak channels and Na+/K+ pumps (voltage-gated channels are closed)

Neuromuscular Junction and Muscle Contraction Overview

• Neuromuscular junction: excitation of a skeletal muscle fiber occurs involving the release of neurotransmitter acetylcholine (ACh) from synaptic vesicles followed by ACh binding to ACh receptors.
• Sarcolemma, T-tubules, and sarcoplasmic reticulum: excitation-contraction coupling occurs.
  • ACh binding triggers propagation of an action potential along the sarcolemma and T-tubules to the sarcoplasmic reticulum, which is stimulated to release Ca2+.
• Sarcomere: crossbridge cycling occurs. –Ca2+ binding to troponin triggers sliding of thin filaments past thick filaments of sarcomeres, as sarcomeres shorten, the muscle contracts.

Neuromuscular Junction: Skeletal Muscle Fiber Excitation

• Calcium entry at synaptic knob.
  • Action potential travels down axon conducting segment, opens voltage-gated Ca2+ channels in synaptic knob
  • Ca2+ diffuses into synaptic knob
  • Ca2+ binds to proteins on surface of synaptic vesicles
• Release of ACh from synaptic knob.
  • Vesicles merge with cell membrane at synaptic knob: exocytosis
  • Thousands of ACh molecules released from about 300 vesicles
• ACh diffuses across cleft, binds to receptors, which excites the fiber.

Excitation-Contraction Coupling

• Stimulation of the fiber is coupled with the sliding of filaments.
• Coupling includes:
  • End-plate potential (EPP)
  • Muscle action potential
  • Release of Ca2+ from the sarcoplasmic reticulum
• End-plate potential (EPP)
  • ACh receptors are chemically gated channels that open when ACh binds to them.
  • Na+ diffuses into the cell through the channels (while a little K+ diffuses out).
  • The cell membrane briefly becomes less negative at the end plate region. –EPP is local, but it leads to opening of voltage-gated ion channels in the adjacent region of the sarcolemma.
• Action potential on the sarcolemma (AP) = rapid rise (depolarization) and fall (repolarization) in the charge of the membrane
  • EPP threshold reached by causing nearby voltage-gated Na+ channels to open.
  • Na+ diffuses into the cell through voltage-gated channels. –Cell depolarizes and becomes +30 mV.
  • The opening of voltage-gated Nat channels results into even more more Na+ entry.
  • Depolarization then spreads down along the membrane and T-tubules.
  • When just after Na+ channels open, the close and voltage-gated K+ channels open.
  • K+ diffuses out of the cell.
  • Cell repolarizes and returns to –90mV.
• Repolarization is then propagated down the membrane and T-tubules.
• The cell is now in a refractory period-unable to respond to another stimulation. AP travels down T-tubules
• Triggers voltage-sensitive calcium channels in T-tubule membrane to release calcium from the terminal cisternae of the sarcoplasmic reticulum
• Ca2+ interacts with myofilaments triggering contraction (attaches to troponin)
• Ca2+ binds to troponin.
  • This triggers crossbridge cycling and moves troponin and tropomyosin so that actin is exposed

Crossbridge Cycling - Steps

• Repeating steps:

1. Crossbridge formation

• Myosin head attaches to exposed binding site on actin

2. Power stroke

• Myosin head pulls thin filament toward center of sarcomere
• ADP and P₁ released

3. Release of myosin head

• ATP binds to myosin head causing its release from actin

4. Reset of myosin head

• ATP split into ADP and P₁
• Provides energy to lift the myosin head readying it for the next actin binding site

Sarcomere Shortening

• Cycling continues as long as Ca2+ and ATP are present.
• Results in sarcomere shortening as Z discs move closer together.
• With the narrowing of H zone and I band, thick and thin filaments remain the same length but slide past each other.

Skeletal Muscle Relaxation

• Events in muscle relaxation:
  • Termination of nerve signal and no ACh release from motor neuron
  • Hydrolysis of ACh by acetylcholinesterase
  • Closure of ACh receptor causes cessation of end plate potential
  • No further action potential generation
  • Closure of calcium channels in sarcoplasmic reticulum
  • Return of Ca2+ to sarcoplasmic reticulum by pumps
  • Return of troponin to original shape
  • Return of tropomyosin blockade of actin's myosin binding sites
  • Return of muscle to original position due to its elasticity

Supplying Energy for Skeletal Muscle Metabolism

• Abundant mitochondria in sarcoplasm for aerobic ATP production (muscle cells have little ATP in storage which is spent after about 5 seconds of intense exertion)
• Myoglobin within cells allows storage of oxygen used for aerobic ATP production
• Glycogen (polysaccharide) is stored for times when fuel is needed quickly
• Ways to generate additional ATP in skeletal muscle fiber:
  • Creatine phosphate
  • Glycolysis
  • Aerobic cellular respiration
• Creatine phosphate (10-15 seconds of additional energy)
  • Molecule containing a high-energy bond between creatine and phosphate
  • Phosphate can be transferred to ADP to form ATP, and is catalyzed by creatine kinase

Glycolysis

• It occurs in cytosol and does not require oxygen to produce ATP.
• Glucose (from muscle's glycogen or through blood) is converted to two pyruvate molecules.
• 2 ATP released per glucose molecule.
• Aerobic cellular respiration.
• It occurs in mitochondria and requires oxygen.
• Pyruvate is oxidized to carbon dioxide.
• Energy used to generate ATP by oxidative phosphorylation that produces a net of 30 АТР.

Lactate Formation

• Under conditions of low oxygen availability, pyruvate is converted to lactate (lactic acid) by lactate dehydrogenase.
• Lactate can be used as fuel by skeletal muscle fiber or enter blood to be taken up by cardiac muscle or liver
• Lactic acid cycle: cycling of lactate to liver where it's converted to glucose, and transport of glucose back to muscle

Oxygen Debt

• Oxygen debt is the amount of additional oxygen needed after exercise to restore pre-exercise conditions in muscle by additional oxygen required to:
  • Replace oxygen on hemoglobin and myoglobin
  • Replenish glycogen
  • Replenish ATP and creatine phosphate
  • Convert lactic acid back to glucose