17. Molecular aspects of muscle contraction, electromechanical coupling

Question 1

Structure of skeletal muscles and skeletal muscle cells

Answer 1

• The skeletal muscle cells are giant cells formed by fusion of embryonic muscle cells (myoblasts). A muscle cell is also called a muscle fiber.
• Mature skeletal muscle fibers have a diameter of 0,01-0,1 mm, while their length is determined by the size of the animal.
• The inner part of the muscle fibers is densely packed with myofibrils.
  
  • Thin (1-2 μm) cylindrical structures that extend throughout the entire muscle fiber.
  • Approx. 80% of the mass of the muscle fibers.
  • Consist of thin, thread-like myofilaments:
    
    • Actin
    • Myosin
  • Myosin is twice as thick as actin.
• Along each myofibril, the myofilaments are organized in a repetitive pattern, of which the smallest unit is called a sarcomere.
  
  • When a striated muscle fiber grows longer, the number of sarcomers in the myofibrils increases.
  • When the diameter of a muscle fiber expands, the number of parallel myofibrils increases.
• Each sarcomere contains two sets of actin filaments. One of the filaments in each set is anchored in a protein lattice that separates two adjacent sarcomers. These dividing walls are called Z-discs.
  
  • In a relaxed muscle there is no overlapping between the two sets of actin filaments in the sarcomers.
• In the middle of the sarcomere the myosin filaments are located, and at the myosin ends the actin overlaps.
• The myosin filaments are interconnected by means of a protein lattice, which is visible as a transverse line (M-line) in the middle of the sarcomere.
• The zones containing only actin form light bands (I-bands).
• The zones containing both actin and myosin form dark bands (A-bands).

Question 2

Proteins in the sarcomere:

Answer 2

• Titin:
  
  • Largest protein of 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.
• Nebulin:
  
  • A stiff, rod-shaped protein, which remains as an integral part of the filament.
  • Determine the direction and placement of actin polymerization during the development of the sarcomere.
  • Protects the developed actin from rearranging effect of other actin-binding proteins.
  • Ensures that all actin filaments are of precisely the same length.
• Alpha-actinin:
  
  • Net-like protein
  • Provides binding site for the actin complexes orienting toward the inner part of the sarcomere.

Question 3

Muscle fibers

Answer 3

• The endoplasmic reticulum of the muscle fibers is called the sarcoplasmic reticulum, and form sleeves around the individual myofibrils.
• The cell membranes gave thin tubular invaginations that traverse the fiber. These T-tubules are branched, and surround each myofibril on either side of the Z-discs.
  
  • In close contact with the SR
  • rapid conduction of the action potential from the surface of the cell to its central parts.

Question 4

Actin:

Answer 4

• Consists of globular actin molecules bound together in a coiled double chain.
• Main component is G-actin, which forms polarized actin-fibers winding up in the double helix.
• On the surface of the helix there is a tropomyosin molecule.
  
  • In resting state, tropomyosin covers the active sites of the actin.
• When troponin complex binds to tropomyosin, the tropomyosin slides into the groove of the two stranded actin helix and previously masked myosin-binding sites become uncovered. –> Cross-bridge cycle starts.

Question 5

Myosin

Answer 5

• Aggregated myosin molecules, with two heavy and four light polypeptide chains.
• The heavy chains are twisted around each other and form an elongated “tail”, a bent “neck”, and a pair of “heads”.
• The four light chains are included in the heads.
• The heads are always pointing against the Z-discs.
• There is a binding site for the myosin heads on each of the globular actin molecules that form the actin filaments. The myosin heads can bind to the actin molecules and exert force on them by altering the angle between the tail and the protruding heads of the myosin molecules.
• This constitutes the basis for the contraction mechanism.
• There are three types of ATPases occur: LC-1, LC-2, LC-3.
  
  • Their types determine the speed of ATPase activity; therefore it determined the efficiency of the whole sarcomere. In fast-twitch type muscle fibers there are LC-2, in slow type ones there are LC-3 chains present.

Question 6

Electro-Mechanical Coupling

Answer 6

• Neural action potentialis transferred to the muscle fibre at the myoneural junction area, result propagation of AP on the myolemma. The electrical signal of the myolemma reaches the triad through the system of T-tubuli, where it is transformed into the calcium-signal. The latter triggers the mechanical responseof the muscle: a contraction(muscle twitch) occurs.

Question 7

Steps of electromechanical coupling

Answer 7

1. Ca release through the function of the TRIAD(T-tubulus + two SR terminal cystern;
2. Activation of muscle proteins(Ca initiates the connection between Tropomyosin-Tn complex leading to the formation of Acto-Myosin komplex)
3. Muscle Contraction(If Ca is available there will be continuous „power strokes” of cross bridges creating contraction through „walk –along” („ratchet”) mechanism).
4. Relaxation follows the process (Ca elimination from IC space as follows) :

a. Na/Ca antiportmechanism (to the EC space !)
b. ATP-dependent Ca-pump to the SR and/or to other compartments (i.e. mitochondria).