Chapter 20 Muscle Physiology

Question 1

Skeletal Muscle Organization

• Skeletal muscle is arranged in a hierarchial fashion
• Muscle
• Fascial
• Muscle fiber (cell)
• Myofibril
• Sarcomeres (from Z disk – Z disk)
• Myofilaments (thick/myosin; thin/actin)

Answer 1

Question 2

Sarcomere EM

• A band- Thick and Thin
• H zone- Thick (center of A)
• M line- middle of H
• I band- portion of the sarcomere between 2 A bands
• Z disc- sarcomere border

Answer 2

Question 3

Sarcomere Filament Geometric Relationship

Thick and thin filaments have a regular geometric arrangement with a hexagonal pattern of thin filaments around a single thick filament.

Answer 3

Question 4

Thin Filament Structure

The primary component of a thin filament is filamentous actin (F-actin); a protein made up of globular subunits (G-actin)

2 other proteins: tropomyosin (filamentous) and troponin (globular) are also associated with actin in the thin filaments

Answer 4

Thick filaments are made up of the protein myosin which has 6 subunits: 2 alpha-helical tails, and 2 heads associated with 2 myosin light chains

Question 5

Sliding Filament Theory of Muscle Contraction

Muscle contraction occurs when thick filaments and thin filaments slide over each other, reducing the overall length of the sarcomere

Question 6

T-Tubule and Sarcoplasmic Reticulum Relationship

Question 7

Excitation-Contraction Coupling

• An action potential from a motor neuron causes release of the neurotransmitter acetylcholine which causes an excitatory postsynaptic potential that reaches threshold and is conducted as an action potential throughout the muscle fiber
• The time between action potential arrival and actual contraction of the muscle is called the latent period

Answer 7

Question 8

Excitation-Contraction Coupling: The Role of Intracellular Ca++

The graph on the right shows the relationship between the action potential (red), Ca2+ levels (green) and contractile force (blue)

Answer 8

Question 9

Ca2+ and Regulation of Muscle Contraction

Isolated muscle preparations require calcium to produce tension/force

Answer 9

Question 10

Ca2+ and ATP and Muscle Contraction

Both Ca2+ and ATP are necessary for muscle contraction

For muscle relaxation ATP is required in the absence of Ca2+

Answer 10

Question 11

Intracellular Ca2+ Level Control

Ca2+ levels within the sarcoplasm are tightly regulated by a “team” of proteins:

1. Voltage-gated dihydropyridine receptor (on T-tubules)
2. Ryanodine receptors ( on SR)
3. Calsequestrin (SR)
4. Ca2+ pumps (SR

Answer 11

Question 12

Triad Receptors

Protein receptors in the T- tubule (dihydropyridine receptor on the left) interact with SR protein receptors (ryanodine receptor) resulting in the release of Ca2+ from within the SR to become available for cross-bridge formation

Answer 12

Question 13

Steps Leading to Ca2+ Release from SR

1. At rest, Ca2+ is sequestered within the SR lumen (green)
2. An AP conducted down the T-tubule causes the ryanodine Ca2+ channel to open in the SR via the voltage-gated dihydropyridine receptor
3. Ca2+ pumps in the SR resequester intracellular Ca2+

Answer 13

Question 14

Ca2+, Troponin, and Tropomyosin in Muscle Contraction Regulation

Recall the two proteins troponin and tropomyosin which are associated with F-actin

Normally the actin’s myosin-binding site is blocked by tropomyosin

Ca2+ dislodges the troponin, which changes the tropomyosin configuration exposing the myosin-binding site for cross-bridging to occur

Question 15

Ca2+ and Muscle Contraction Regulation

Answer 15

Question 16

The Ratchet Effect

Answer 16

Question 17

Contraction-Relaxation Cycle Summary

1. Plasma membrane depolarization
2. AP conduction into middle of cell via T-tubule
3. Voltage-sensitive dihydropyridine receptor changes conformation resulting in the opening of ryanodine receptors in the SR
4. Ca2+ released into myoplasm from SR
5. Ca2+ binds to troponin complex causing a conformational change exposing myosin-binding sites on the actin molecule

Answer 17

6. Myosin head forms a “cross-bridge” with actin via a conformational change called the “power stroke” which pulls the actin filament towards the center of the sarcomere
7. ATP hydrolysis at the myosin head allows the myosin molecule to “recock”; several cross-bridges are then formed, broken and reformed
8. Ca2+ pumps in the SR resequester Ca2+ preventing the formation of new cross-bridges

Question 18

Muscle Contraction Mechanics

Muscle contractions without actual shortening are called isometric contractions

Muscle contractions with muscle shortening are called isotonic contractions

Answer 18

Question 19

Contraction of Skeletal Muscle

• Motor unit
  
  • Motor neuron entering muscle branches to many fibers
    
    • 1 motor nerve/fiber
    • many fibers/nerve
  • Motor unit = motor neuron and all muscle fibers that it innervates
  • Size of unit varies
    
    • small - two muscle fibers/unit (larynx, eyes)
    • large - hundreds, thousands/unit (biceps, gastrocnemius, lower back muscles)
  • Fibers in motor unit spread throughout muscle for coverage

Answer 19

• Graded muscle responses
  
  • Force of muscle contraction varies depending on need
  • A twitch does not provide much force
  • Contraction force can be altered 3 ways:
    
    • Changing frequency of stimulation (i.e. tetanic contractions)
    • Changing muscle length (length-tension relationships)
    • Changing force of stimulation (increasing # of motor units contracting - recall that a single muscle fiber does not increase the size of its contraction with an increased stimulus (all-or-none principle)

Question 20

Contractile States: Twitch/Tetanus

Under normal conditions, prolonged contraction can be achieved by increasing the frequency of APs arriving at the muscle fiber

Peak tension is developed during a tetanic contraction

The increased tension compared to a twitch is largely due to increased availability of intracellular Ca2+

Answer 20

Question 21

Length-Tension Curve for Sarcomere Contraction

Maximal force (tension) is generated when there is an optimal amount of overlap between the thick and thin filaments.

Under normal conditions, skeletal muscle fibers are in the plateau portion of the above curve.

Answer 21

Question 22

Length-Tension Relationship for the Muscle as a Whole

Like an individual sarcomere, the muscle as a whole also demonstrates an optimal length for producing maximal tension.

Answer 22

Question 23

Sources of ATP for Muscle Contraction

The large amounts of ATP needed for myosin recocking and Ca2+ pumps can be produced anaerobically or aerobically

In addition to cellular ATP production, muscle fibers contain creatine phosphate which is a ready short-term source of phosphate groups for ATP formation

Answer 23

Question 24

Muscle Fiber Types

• Different fiber types have evolved in vertebrates with different contractile and metabolic properties
• These adaptations allow for a large variety of activities from quick escapes, to prolonged low-intensity activities
  
  • Tonic fibers: contract very slowly and do not product twitches; found in postural muscles of lower vertebrates and mammalian muscle spindles
  • Slow-twitch (Type I) fibers: contract and fatigue slowly (red meat)
  • Fast-twitch/oxidative (Type IIa) fibers: contract quickly and fatigue relatively slowly (not as slowly as Type I fibers)
  • Fast-twitch/glycolytic (Type IIb) fibers: contract and fatigue rapidly (white meat)

Question 25

Summary of Muscle Fiber Type Properties

Question 26

Muscle Fiber Types

A particular muscle typically has a mix of fiber types as illustrated by this specially stained electron micrograph

Question 27

Smooth Muscle

• Single-unit smooth muscles
  
  • Gap junctions
  • Walls of vertebrate visceral organs
  • Myogenic – activation of a few fibers can generate contraction that moves in a wavelike manner
• Multi-unit smooth muscles
  
  • No gap junctions
  • Iris of eye, blood vessel muscles
  • Neurogenic - Act independently and contract only when stimulated by neurons or hormones
• Smooth muscles contain actin and myosin, but they lack sarcomeric arrangement.

Question 28

Regulation of Smooth Muscle Contraction

• Smooth muscles
  
  • Lack troponin
  • Have caldesmon
    
    • binds to thin filaments
    • prevents myosin:actin binding
• Caldesmon is removed by two different mechanisms:

1. After calmodulin and calcium bind, they bind to caldesmon, freeing up the myosin binding sites on actin.
2. Calcium-calmodulin works to phosphorylate myosin allowing it to interaction with actin

• Like skeletal muscle, all of these mechanisms act by allowing actin and myosin to form cross-bridges; intracellular Ca2+ levels are important for regulating contraction as with skeletal muscle.

Answer 28

Question 29

Characteristics of Vertebrate Muscle Fiber Types

Answer 29