Topic 18 - Molecular aspects of muscle contraction and electromechanical coupling Flashcards

1
Q

Words to include in electromechanical coupling

A
  • 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
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2
Q

Words to include in molecular aspects of muscle contraction

A
  • 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
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3
Q

Electromechanical coupling

Definition

A

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

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4
Q

Electromechanical coupling

From AP to muscle contraction

A
  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
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5
Q

Electromechanical coupling

Stages of electromechanical coupling

A
  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
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6
Q

Electromechanical coupling

Definition of the triad

A
  • Triad: excitation-contraction coupling
  • Diad in cardac muscles
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7
Q

Electromechanical coupling

Give the receptros in the T-tubule

A
  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
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8
Q

Molecular aspects of muscle contraction

Sarcomere

A
  • 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
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9
Q

Molecular aspect of muscle contraction

Actin

A
  • 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
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10
Q

Molecular aspect of muscle contraction

Myosin

A
  • Composed of:
    • 2 heavy polypeptide chains
      • Forming a tail, neck and a pair of heads
    • 4 light polypeptide chanis
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11
Q

Molecular aspect of muscle contraction

Titin

A
  • 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
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12
Q

Molecular aspect of muscle contraction

Nebulin

A
  • 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
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13
Q

Molecular aspect of muscle contraction

Alpha-actin

A
  • Net-like protein
  • Provides binding site for actin
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14
Q

Molecular aspects of muscle contraction

The cross bridge cycle

A
  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
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15
Q

Molecular aspects of muscle contraction

Ca2+ dependence of the cross-bridge cycle

A
  • 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
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16
Q

Molecular aspects of muscle contraction

ATP dependence of the cross-bridge cycle

A
  • 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
17
Q

Molecular aspects of muscle contraction

Define the “Ratchet mechanism”

A
  • The Ratchet mechanism: Individual myosin heads need to work asynchronously to cause contraction
18
Q

Molecular aspects of muscle contraction

Removal of calcium

A
  • 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