Topic 18 - Molecular aspects of muscle contraction and electromechanical coupling

Question 1

Words to include in electromechanical coupling

Answer 1

• Myogenic action potential
• Neural action potential
• Muscle fiber
• Nyoneural area
• Myolemma
• Electrical signal
• Triad
  
  • Excitation-contraction coupling
  • Diad (cardic)
• T-tubule
• Calcium signal
• Mechanical response
• Contraction
• Neuro-muscular junction
• Voltage gated L-type Ca²⁺ channels
• Ryanoid-Ca²⁺ channel
• Conformational change
• Sarcoplasmic reticulum (SR)
• Ca²⁺
• Ca²⁺-channels
• Sacromer
• Ca²⁺ release
• Muscle proteins
• Muscle contraction
• Relaxation
  
  • Na/Ca antiporter mechanism
  • ATP-dependent Ca-pump
• L-type receptor
  
  • Dihydropyridine (DHP)
    
    • Potential dependent DHP protein
  • Modified calcium channels
• T-type calcium channels
  
  • Ryanoid

Question 2

Words to include in molecular aspects of muscle contraction

Answer 2

• Myofibrils
• Sacromer
  
  • Thin filaments
    
    • Actin
      
      • Globular
      • G-actin
        
        • Polarized actin-fibers
        • Double helix
  • Thick filaments
    
    • Myosin
      
      • Heavy polypeptide chains (2 stk)
      • Light polypeptide chains (4 stk)
  • I band
  • A band
  • Z line
  • Titin (protein)
  • Nebulin (protein)
  • Alpha-actin (protein)
• Endoplasmic reticulum
  
  • Sacroplasmic reticulum
• Cross bridge cycle
  
  • Calcium binding
  • Actin-myosin attached
  • Sliding
  • ATP
  • ATP binding
  • Actin-myosin detach
  • Resting state in contraction
  • Resting state in relaxation
• Tropomyosin
• ATP
  
  • ADP
  • Pi
• Myosin head
• Cocking of myosin head
• Power stroke
  
  • Power stroke 1
  • Power stroke 2
• Rigor mortis
• Ratchet mechanism
  
  • Asynchronously contraction
• Sodium / calcium antiporter
• Calcium-ATPase
• Secondary active transport
• ATP dependent calcium pumps
• Sequesters
  
  • Compartmetabolize calcium
• Mitochindrion
• Sarcoplasmic reticulum

Question 3

Electromechanical coupling

Definition

Answer 3

Electromechanical coupling: starts with the myogenic AP and ends with the contraction of the muscle fiber (followed by relaxation)

Question 4

Electromechanical coupling

From AP to muscle contraction

Answer 4

1. AP reaches the myolemma from the neuromuscular junction
2. AP reaches the L-type voltage gated Ca²⁺-channels in the T-tubule
3. L-type voltage gated Ca²⁺-channelss open
4. Because the L-type voltage gated Ca²⁺-channels open, the ryanoid-Ca²⁺ will also open
   
   • Due to the conformational change
5. From the sarcoplasmic reticulum a lot of Ca²⁺ will get into the IC part of the cell
6. The Ca²⁺-channels on the myolemma will open
   
   • Ca²⁺-influx from the EC
7. Result: IC Ca²⁺ level will be high around the sacromer
8. Contraction

Question 5

Electromechanical coupling

Stages of electromechanical coupling

Answer 5

1. Ca²⁺ release
2. Activation of muscle proteins
3. Muscle contraction
4. Relaxation
   
   • Na/Ca antiporter mechanism
   • ATP-dependent Ca-pump to the SR
   • And/or to other compartments

Question 6

Electromechanical coupling

Definition of the triad

Answer 6

• Triad: excitation-contraction coupling
• Diad in cardac muscles

Question 7

Electromechanical coupling

Give the receptros in the T-tubule

Answer 7

1. L-type receptor - dihydropyridine (DHP)
   
   • Undergo conformational change
   • Modified calcium channels
2. T-type calcium channels - ryanoid
   
   • ​​On the IC side
   • Will open after L-type receptor is activated

Question 8

Molecular aspects of muscle contraction

Sarcomere

Answer 8

• Sarcomere: The sliding filament​
• Composed of:
  
  • Actin
    
    • ​Thin filaments
    • Each sarcomere contains 2 sets of actin filaments
  • Myosin
    
    • ​Thick filaments
  • I band
    
    • ​Part of the sarcomere that contains the filaments
  • A band
    
    • ​Area of overlap between thin and thick filament
  • Z line
    
    • ​Attaches neighboring sarcomeres
  • Regulatory proteins
    
    • ​Titin
    • Nebulin
    • Alpha-actinin
      
      • ​Provides binding site for actin
• The inner part of the muscle fibers is densly packed with myofibrils
• The endoplasmic reticulum of the muscle fibers is called the sarcoplasmic reticulum

Question 9

Molecular aspect of muscle contraction

Actin

Answer 9

• Thin filaments
• Consists of globular actin molecules bound together in a coiled double chain
• Main component is G-actin
  
  • ​Formes polarized actin-fibers winding up in the double helix
  • on the surface of the helix there is a tropomyosin molecule

Question 10

Molecular aspect of muscle contraction

Myosin

Answer 10

• Composed of:
  
  • 2 heavy polypeptide chains
    
    • ​Forming a tail, neck and a pair of heads
  • 4 light polypeptide chanis

Question 11

Molecular aspect of muscle contraction

Titin

Answer 11

• Protein in the sarcomere
• Largest protein in the body
• Originates from the Z lines and ends in the myosin bundles
• Ensures a precise return of actin and myosin bundles to their original position even after extensive stretch

Question 12

Molecular aspect of muscle contraction

Nebulin

Answer 12

• Remains as an integral part of the filament
• Determine the direction and placement of actin polymerization during the development of the sarcomere
• Ensures that all actin filaments are of the same length

Question 13

Molecular aspect of muscle contraction

Alpha-actin

Answer 13

• Net-like protein
• Provides binding site for actin

Question 14

Molecular aspects of muscle contraction

The cross bridge cycle

Answer 14

1. Relaxation = myosin heads (cross-bridge) is charged
   
   • Cocking of myosin heads
   • ADP + Pi
2. Neural AP results in Ca²⁺ release, TnC-Ca^{<strong>2+</strong>} pulls off
   
   • ​Tropomyosin form actin, freeing myosin binding sites
   • Cross bridge bind to actin
3. After cross-bridge binds to actin, energy is deliberated = contraction (lowest energy status). This is called the power-stroke and happens in 2 steps:
   
   • Power-stroke 1: Myosin heads tilts 40˚ still glued to actin
   • Power-stroke 2: ADP dissociation resulting in further enegy deliberation and in +5˚ conformational change
4. Ca²⁺ is removed from the surrounding area of the filaments
   
   • Myosin detaches from actin
   • Tropomyosin slides back

Question 15

Molecular aspects of muscle contraction

Ca²⁺ dependence of the cross-bridge cycle

Answer 15

• Parturient paries / permanent relaxation
  
  • In the absence of Ca²⁺, myosin can not bind to actin due to the blocked binding sites, because tropomyosin will not be lifted

Question 16

Molecular aspects of muscle contraction

ATP dependence of the cross-bridge cycle

Answer 16

• Rigor mortis / cadaverous rigidity
  
  • In the absence of ATP, actin and myosin can not dissociate
    
    • Usually, ATP attaches to myosin and the myosin head will detach

Question 17

Molecular aspects of muscle contraction

Define the “Ratchet mechanism”

Answer 17

• The Ratchet mechanism: Individual myosin heads need to work asynchronously to cause contraction

Question 18

Molecular aspects of muscle contraction

Removal of calcium

Answer 18

• Removal mechanisms are ATP dependent:
  
  1. ​​Sodium / calcium antiporter
     
     • ​​Removes calcium with secondary active transport
  2. Calcium repumping into SR
     
     • ​​Conducted by ATP dependent calcium pumps
  3. Sequesters
     
     1. ​Cell organelles able to compartmentalize calcium