Ch 12

MUSCLE PHYSIOLOGY: COMPREHENSIVE STUDY NOTES

TYPES OF MUSCLE TISSUE

Three Major Muscle Types

1. Skeletal Muscle
   
   

   • Function: Body movement

   • Control: Voluntary (somatic motor neurons)

   • Structure: Striated

2. Cardiac Muscle
   
   

   • Function: Moves blood through circulatory system

   • Control: Involuntary (autonomic innervation, spontaneous contraction)

   • Structure: Striated

3. Smooth Muscle
   
   

   • Function: Internal organs and tubes

   • Control: Involuntary (autonomic innervation, spontaneous, endocrine)

   • Structure: Non-striated

Muscle Fiber Characteristics

SKELETAL MUSCLE STRUCTURE

Hierarchical Organization

• Muscle → Fascicles → Muscle fibers → Myofibrils → Myofilaments

• Muscle fiber = single muscle cell (long, cylindrical with many nuclei)

• Satellite cells = muscle stem cells

• Myofibrils = organized bundles of contractile and elastic proteins

Muscle Fiber Anatomy

• Sarcolemma = muscle cell membrane

• Sarcoplasm = muscle cell cytoplasm

• Sarcoplasmic reticulum (SR) = specialized endoplasmic reticulum that stores Ca²⁺

  • Has longitudinal tubules with enlarged end regions called terminal cisternae

• T-tubules = extensions of sarcolemma that penetrate into the cell

  • Allow action potentials to reach internal structures

  • Associate with terminal cisternae of SR

CONTRACTILE PROTEINS

Major Protein Types

1. Contractile proteins (thick & thin filaments)
   
   

   • Myosin (thick filament)

   • Actin (thin filament)

2. Regulatory proteins
   
   

   • Tropomyosin

   • Troponin

3. Giant accessory proteins
   
   

   • Titin

   • Nebulin

Myosin (Thick Filaments)

• Structure: 2 identical protein chains

  • Each with 1 large heavy chain (tail-hinge-head)

  • 2 smaller light chains wrapped around lower neck region

• Heavy chain on heads: motor domain (myosin ATPase) with actin binding sites

• About 250 myosin molecules join to create one thick filament

Actin (Thin Filaments)

• G-actin = Actin monomer

• F-actin = Actin polymer

• Thin filament = 2 F-actin polymers twisted together

Accessory Proteins

• Titin

  • Stabilizes position of contractile elements

  • Provides elasticity to return stretched muscles to resting length

• Nebulin

  • Inelastic protein

  • Aligns actin filaments

SARCOMERE STRUCTURE

• Sarcomere = contractile unit of myofibril (one repeat of the banding pattern)

• Z disks = attachment sites for thin filaments

• I band = light band containing only thin filaments (actin)

• A band = dark band containing thick filaments (myosin) and overlapping thin filaments

• H zone = clear area in middle of A band (thick filaments only)

• M line = middle line where thick filaments attach

MUSCLE CONTRACTION

Key Terms

• Muscle tension: Force created by contracting muscle

• Load: Weight or force opposing contraction

• Contraction: Creation of tension in muscle (ATP-dependent)

• Relaxation: Release of tension

• Muscle twitch: One contraction-relaxation cycle in intact muscle

Sliding Filament Theory

• Theory explaining contraction at molecular level (Huxley & Niedergerke, 1954)

• During contraction:

  • Filaments don't change length but slide past each other

  • Sarcomere shortens

  • Z disks move closer together

  • I band and H zone nearly disappear

  • A band remains constant length

Cross-Bridge Cycle

1. Myosin head binds to actin (forming cross-bridge)

2. Power stroke: Myosin heads push thin filaments toward center of sarcomere

3. ATP binding causes myosin to release actin

4. ATP hydrolysis (myosin ATPase) places myosin head in "cocked position"

5. Cycle repeats

Role of Calcium in Contraction

• At rest, tropomyosin blocks myosin binding sites on actin

• Troponin (complex of 3 proteins) controls positioning of tropomyosin

• When Ca²⁺ binds to troponin:

  • Tropomyosin moves

  • Myosin binding sites on actin are exposed

  • Cross-bridge cycling can occur

Rigor State

• Myosin heads tightly bound to actin

• No nucleotides (ATP/ADP) bound to myosin

• Rigor mortis: After death, ATP is exhausted → myosin remains bound to actin in rigor state

EXCITATION-CONTRACTION COUPLING

Process

1. ACh released by motor neuron

2. ACh binds receptors → Action potential in muscle fiber

3. Action potential travels along T-tubules

4. Dihydropyridine (DHP) receptors sense voltage change

5. DHP receptors trigger ryanodine receptors (RyR)

6. Ca²⁺ released from sarcoplasmic reticulum

7. Ca²⁺ binds to troponin

8. Contraction occurs

Relaxation Process

1. Ca²⁺ dissociates from troponin

2. Ca²⁺ pumped back into SR by Ca²⁺-ATPase

3. Tropomyosin blocks myosin binding sites

4. Contraction ends

Timing

• Latent period: Time required for Ca²⁺ release and binding to troponin

• Contraction phase: Muscle tension increases to maximum

• Relaxation phase: Elastic elements return sarcomeres to resting length

ENERGY REQUIREMENTS AND METABOLISM

ATP Uses in Muscle

1. Contraction: Cross-bridge movement and release

2. Relaxation: Pump Ca²⁺ back into SR

3. After E-C coupling: Restore Na⁺ and K⁺ gradients

Energy Storage

• ATP stores in muscle are limited (enough for ~8 twitches)

• Phosphocreatine: Stores energy from ATP in high-energy bonds

Energy Production Pathways

1. With oxygen (aerobic):
   
   

   • Glycolysis → Pyruvate oxidation → Citric acid cycle → Oxidative phosphorylation

   • Yields ~30 ATP per glucose

   • Can also utilize fatty acids

2. Without oxygen (anaerobic):
   
   

   • Anaerobic glycolysis → Lactic acid

   • Only 2 ATP per glucose

   • Quicker than aerobic metabolism

   • Used during strenuous exercise

MUSCLE FATIGUE

Central vs. Peripheral Fatigue

• Central fatigue: Mechanisms arise in CNS

• Peripheral fatigue: Mechanisms arise in neuron or muscle

Fatigue Causes Based on Exercise Type

1. Extended submaximal exercise:
   
   

   • Depletion of glycogen stores (could affect Ca²⁺ release from SR)

2. Short-duration maximal exercise:
   
   

   • Increased levels of inorganic phosphate (Pi)

   • May slow Pi release from myosin → alter power stroke

   • Decreased Ca²⁺ release (calcium phosphate formation)

3. Maximal exercise:
   
   

   • K⁺ leaves muscle fiber → increased extracellular [K⁺] → alteration of membrane potential

   • Changes Na⁺/K⁺ ATPase activity

SKELETAL MUSCLE FIBER TYPES

Classification by Speed and Fatigue Resistance

1. Slow-Twitch (ST or Type I)
   
   

   • Twitch may last up to 10 times longer

   • Used constantly (maintain posture, walking)

   • Rely primarily on oxidative phosphorylation

   • More resistant to fatigue

   • More mitochondria and blood vessels

   • Higher myoglobin content ("red muscle")

2. Fast-Twitch Oxidative-Glycolytic (FOG or Type IIA)
   
   

   • Develop tension 2-3 times faster than ST

   • Twitch lasts about 7.5 msec

   • Use both oxidative and glycolytic metabolism

   • Used occasionally

   • Intermediate fatigue resistance

3. Fast-Twitch Glycolytic (FG or Type IIB/IIX)
   
   

   • Split ATP more rapidly

   • Pump Ca²⁺ into SR more rapidly

   • Rely primarily on glycolytic metabolism

   • More easily fatigued

   • Good for fine quick movements (e.g., playing piano)

FORCE OF CONTRACTION

Single Twitches vs. Summation

• Single twitches: Long interval between action potentials → complete relaxation

• Summation: Shorter interval between action potentials → incomplete relaxation between contractions

Tetanus

• Incomplete/unfused tetanus: Partial relaxation between contractions

• Complete/fused tetanus: No relaxation between contractions (maximal contraction)

• Tension increases with increased firing rate from motor neuron

MOTOR UNITS

• Motor unit: One somatic motor neuron and all muscle fibers it innervates

• Muscle fibers in a motor unit are of the same type

• Each motor unit contracts in all-or-none manner

• A muscle may have many motor units of different types

Motor Unit Recruitment

• Force variation by:
  
  

  1. Type of active motor units

  2. Number of motor units that respond

• Recruitment order (size principle):
  
  

  1. Slow-twitch (lowest threshold) → WEAK STIMULUS

  2. Fast-twitch oxidative-glycolytic (medium threshold) → STRONGER STIMULUS

  3. Fast-twitch glycolytic (highest threshold) → STRONGEST STIMULUS

SMOOTH MUSCLE

Classifications

1. By location:
   
   

   • Vascular, gastrointestinal, urinary, respiratory, reproductive, ocular

2. By contraction pattern:
   
   

   • Phasic: Periodic contraction/relaxation cycles (intestines)

   • Tonic: Sustained contraction (sphincters, blood vessel wall)

3. By communication with neighboring cells:
   
   

   • Single-unit (visceral): Electrically connected via gap junctions

   • Multi-unit: Not linked, independent

Structural Differences from Skeletal Muscle

• Small, spindle-shaped cells with one nucleus

• No sarcomeres

• No T-tubules but have caveolae (membrane invaginations)

• Variable amount of SR, less organized

• More actin (10-15 actin:1 myosin ratio)

• Longer myosin filaments with heads covering entire surface

• Extensive cytoskeleton (intermediate filaments and dense bodies)

• More stretching capability

Smooth Muscle Contraction Mechanism

1. Increase in cytosolic Ca²⁺ (from both SR and extracellular fluid)

2. Ca²⁺ binds to calmodulin (not troponin)

3. Ca²⁺-calmodulin complex activates myosin light chain kinase (MLCK)

4. MLCK phosphorylates myosin light chain (MLC)

5. Phosphorylation activates myosin ATPase → contraction

6. Dephosphorylation of MLC by MLC phosphatase (MLCP) → relaxation

Calcium Sources in Smooth Muscle

1. From SR:
   
   

   • Ryanodine receptor (RyR)

   • IP₃-receptor channel (IP₃R)

   • Ca²⁺-induced Ca²⁺ release (CICR)

2. From extracellular fluid via:
   
   

   • Voltage-gated Ca²⁺ channels

   • Receptor-operated calcium channels (ROCC)

   • Mechanically-gated Ca²⁺ channels (stretch-activated)

Contraction Types in Smooth Muscle

1. Electromechanical coupling: Contraction by electrical signaling

2. Pharmacomechanical coupling: Contraction by chemical signaling (GPCR → PLC pathway)

3. Myogenic contraction: Response to stretch without neural/hormonal input

Smooth Muscle Electrical Properties

• Can depolarize and hyperpolarize
  
  

• Membrane potential oscillates
  
  

• Contraction can occur:
  
  

  • After an action potential

  • After graded (subthreshold) potential

  • Without change in membrane potential

• Slow-wave potentials: Cyclic depolarization-repolarization
  
  

• Pacemaker potentials: Regular depolarizations beyond threshold
  
  

Smooth Muscle Regulation

• Under antagonistic control of sympathetic and parasympathetic branches of ANS

• Chemical signals can have different effects on different tissues (e.g., epinephrine α vs β₂)

• Paracrine signals:

  • Nitric oxide (NO) relaxes smooth muscles of blood vessels

  • Histamine constricts smooth muscle of airways

• Force of contraction depends on amount of Ca²⁺ entering the cell

• Fine control achieved through recruitment of more fibers

CARDIAC MUSCLE

Characteristics

• Striated appearance like skeletal muscle

• Shorter branching fibers with one nucleus

• Fibers electrically linked via gap junctions (intercalated disks)

• Contains T-tubules and sarcoplasmic reticulum

• Uses troponin and tropomyosin (like skeletal muscle)

• Ca²⁺ from both extracellular fluid and SR

• Contraction speed intermediate between skeletal and smooth muscle

• Autorhythmic (can initiate contraction without external stimulus)

• Under autonomic neural control

• Influenced by epinephrine

COMPARISON OF MUSCLE TYPES

KEY CONCEPTS SUMMARY

1. Muscle Types: Skeletal (voluntary, striated), cardiac (involuntary, striated), and smooth (involuntary, non-striated)
   
   

2. Skeletal Muscle Contraction:
   
   

   • Sliding filament theory - filaments don't change length but slide past each other

   • Cross-bridge cycling requires ATP

   • Ca²⁺ signaling via troponin/tropomyosin system

   • Excitation-contraction coupling links electrical signals to mechanical response

3. Energy Use in Muscle:
   
   

   • ATP required for contraction, relaxation, and ion balance

   • Phosphocreatine provides quick energy storage

   • Aerobic and anaerobic pathways for ATP production

4. Skeletal Fiber Types:
   
   

   • Slow-twitch (Type I): fatigue-resistant, oxidative

   • Fast-twitch oxidative-glycolytic (Type IIA): intermediate

   • Fast-twitch glycolytic (Type IIB/IIX): powerful, easily fatigued

5. Motor Units and Force Generation:
   
   

   • Force increases with recruitment of additional motor units

   • Recruitment follows size principle (smallest/slow-twitch first)

   • Tetanus increases force through temporal summation

6. Smooth Muscle Contraction:
   
   

   • Ca²⁺-calmodulin-MLCK phosphorylation pathway

   • Multiple Ca²⁺ sources (SR and extracellular)

   • Multiple control mechanisms (electrical, chemical, mechanical)

7. Cardiac Muscle:
   
   

   • Combines features of both skeletal and smooth muscle

   • Autorhythmic capability

   • Electrically coupled via gap junctions

CHAPTER 12 REVIEW QUESTIONS

1. List the three types of muscles, their functions, similarities, and differences.

• Skeletal Muscle: Voluntary, striated muscle responsible for movement, posture, and heat production. Multinucleated and attached to bones. Requires nervous system stimulation.

• Cardiac Muscle: Involuntary, striated muscle found only in the heart. It contracts rhythmically and autonomously, regulated by the autonomic nervous system and pacemaker cells.

• Smooth Muscle: Involuntary, non-striated muscle found in walls of hollow organs (digestive tract, blood vessels). It regulates organ function, contracts slowly, and is controlled by hormones and autonomic signals.

• Similarities: All muscle types generate force through actin and myosin interaction.

• Differences: Skeletal muscle is voluntary, while cardiac and smooth muscle are involuntary. Cardiac muscle has intercalated discs; smooth muscle lacks striations and sarcomeres.

2. Relationship between muscle, muscle fiber, and fascicle

• A muscle is composed of multiple fascicles, which are bundles of muscle fibers (muscle cells).

3. Components of skeletal muscle besides muscle fibers

• Connective tissue (endomysium, perimysium, epimysium), blood vessels, nerves, satellite cells, and extracellular matrix.

4. Definitions of terms

• Sarcolemma: The plasma membrane of a muscle fiber.

• Sarcoplasm: The cytoplasm of a muscle fiber containing myofibrils, mitochondria, and glycogen granules.

• Myofibril: Cylindrical contractile elements within muscle fibers composed of sarcomeres.

• Sarcoplasmic Reticulum (SR): Specialized endoplasmic reticulum storing and releasing calcium for contraction.

• Transverse Tubules (T-tubules): Invaginations of the sarcolemma that facilitate action potential conduction.

• Triad: A structure formed by one T-tubule and two adjacent terminal cisternae of the SR.

5. Glycogen granules in muscle cytoplasm

• Provide an immediate energy source for ATP production during muscle contraction.

6-8. Proteins in the myofibril

• Contractile proteins: Actin (thin filament) and Myosin (thick filament).

• Regulatory proteins: Troponin and Tropomyosin (control interaction of actin and myosin).

• Giant accessory proteins: Titin (provides elasticity and stabilizes myosin) and Nebulin (aligns actin filaments).

9-10. Myosin and thin filament structure

• Myosin: Has a tail, hinge, and two heads with ATPase activity. Heads form crossbridges with actin.

• Thin filament: Comprised of G-actin (globular) subunits forming F-actin (filamentous) strands.

11. Actin-myosin relationship and crossbridge

• Myosin heads bind to actin forming crossbridges, essential for contraction.

12-13. Sarcomere structure and elements

• A band: Dark region containing thick filaments (myosin).

• H zone: Central part of A band with only thick filaments.

• I band: Light region containing only thin filaments.

• M line: Middle of sarcomere anchoring thick filaments.

• Z disk: Anchors thin filaments and marks sarcomere boundaries.

14. Functions of titin and nebulin

• Titin: Elastic protein maintaining sarcomere structure and passive tension.

• Nebulin: Regulates thin filament alignment.

15. Definitions

• Muscle tension: Force generated during contraction.

• Load: External force on a muscle.

• Contraction: Activation of muscle fibers to generate force.

• Relaxation: Reduction of tension as filaments return to resting position.

16. Major steps of muscle contraction

1. Action potential reaches neuromuscular junction.

2. Acetylcholine (ACh) is released, binding to receptors.

3. AP propagates through T-tubules.

4. SR releases Ca2+.

5. Ca2+ binds to troponin, shifting tropomyosin.

6. Myosin binds actin (crossbridge formation).

7. Power stroke occurs (ATP hydrolysis).

8. Muscle contracts.

17-21. Sliding Filament Theory and contraction details

• Theory: Contraction occurs as thin filaments slide over thick filaments.

• Z disks move closer together.

• A band remains constant (myosin does not change length).

• I band and H zone shorten/disappear (overlapping increases).

22-25. Power stroke and contractile cycle

• Power stroke: Myosin pulls actin toward M line.

• Cycle: Rigor state → ATP binds → Myosin detaches → ATP hydrolysis → Myosin reattaches → Power stroke.

26-29. Excitation-Contraction (E-C) Coupling and relaxation

• Excitation: ACh binds → Na+ influx → AP propagates.

• Ca2+ released from SR.

• Contraction cycle begins.

• Relaxation: Ca2+ reabsorbed into SR via Ca2+-ATPase.

• Latent period: Time between AP and contraction onset.

30-33. ATP and muscle fatigue

• Phosphocreatine: Short-term ATP source.

• Aerobic: 32 ATP per glucose.

• Anaerobic: 2 ATP per glucose.

• Fatigue: Caused by metabolic depletion, ion imbalance, and neural factors.

• Central vs. Peripheral fatigue: Central = brain-related, Peripheral = muscle-related.

34-38. Muscle fiber classification and fatigue resistance

• Slow-twitch oxidative (Type I): Fatigue-resistant, aerobic, high myoglobin.

• Fast-twitch oxidative-glycolytic (Type IIa): Intermediate properties.

• Fast-twitch glycolytic (Type IIx): Fast but fatigues quickly.

39-44. Force of contraction and motor units

• Summation: Increased stimulus frequency = increased force.

• Tetanus: Unfused = partial relaxation, Fused = sustained contraction.

• Motor unit: A motor neuron and all its innervated fibers.

• Recruitment: More motor units activated for greater force.

45-59. Smooth muscle physiology

• Types: Vascular, gastrointestinal, urinary, respiratory, reproductive, ocular.

• Single-unit: Cells connected via gap junctions (functional syncytium).

• Multi-unit: Independent cells (e.g., iris, airways).

• Differences from skeletal muscle: No sarcomeres, uses calmodulin instead of troponin, slow contraction, variable stimuli.

• Contraction mechanism: Ca2+ → Calmodulin → MLCK → Myosin phosphorylation → Contraction.

• Relaxation: Myosin phosphatase dephosphorylates myosin.

• Pacemaker vs. slow wave potentials: Pacemaker = rhythmic depolarizations, Slow wave = fluctuating membrane potential.

• Regulation: Neurotransmitters (ACh, NE), hormones (oxytocin, adrenaline), paracrines (NO, histamine).