Muscle Sarcomere Structure and Function

Sarcomere Structure & Function

Sarcomere

  • Functional contractile unit of muscle.
Bands and Zones:
  • A band (anisotropic): Darker band.
  • I bands (isotropic): Lighter bands.
  • H zone: Central region of A band; contains only thick (myosin) filaments at rest.
  • Z disks: Define the length of the sarcomere.
  • M line: Middle portion of the sarcomere.
Changes During Contraction:
  • H zone becomes smaller as cross-bridges form and pull Z disks closer.
  • I band becomes smaller as Z disks come closer.

Structural Components of the Sarcomere

  • Actin.
  • Tropomyosin.
  • Troponin.
  • Nebulin.
  • Myosin. (thick filament).
  • C, X, and H proteins (help maintain sarcomere alignment).
  • Z Line: Endpoint of sarcomere, made of alpha-actinin and desmin proteins.
  • M Line: Middle portion of sarcomere, made of various proteins (M protein, myomesmin, myosin-binding protein, MRF1, MCK proteins).
  • Titin: Large protein made of Novex-3 and Obscurin.

Detailed Sarcomere Structure

  • Z line (blue ends), actin attached.
  • M band in the middle.
  • Myosin proteins branch out from M band.
  • Associated proteins present in each region.

Illustration of Substructures and Proteins

  • Obscurin around the M line.
  • Titin proteins.

Sarcomere Length

  • Defined by Z lines or Z disks.
Bands:
  • H zone.
  • A band.
  • I band.
  • Remember, some of these bands shorten during muscle contraction.

Actin (Thin Filament)

Composition:
  • Approximately 350 monomers of actin.
  • Approximately 50 molecules of tropomyosin and troponin.
G Actin:
  • Individualized.
  • Binding site becomes exposed to allow myosin head attachment for cross-bridge formation.
Troponin:
  • Complexes found every G actin monomer.
Subunits:
  • Troponin T: Binds to tropomyosin.
  • Troponin C: Binds calcium.
  • Troponin I: Inhibitory subunit.
Calcium Binding:
  • Causes a conformational change in tropomyosin shape.
  • Reveals the myosin binding site on actin.
Crossbridge Formation:
  • Calcium release, binding, and shifting of tropomyosin expose actin binding site.
  • Myosin heads attach to binding site, forming a crossbridge.

Nebulin

  • Large sarcomeric protein coextensive with actin filament in skeletal muscle sarcomere.
Functions:
  • Involved in thin filament length specification (controls length).
  • Helps regulate muscle contraction.
  • Deficiencies lead to reduced force production due to reduced myofilament calcium sensitivity and altered crossbridge cycling.
  • Plays a role in calcium homeostasis.
  • May be related to the development of high levels of muscle force efficiently.
  • Plays a role in the assembly and alignment of Z lines/disks.

Myosin

  • Hexameric (six-component) molecule.
Composition:
  • One pair of heavy chains (approximately 200kD200 kD).
  • Two pairs of light chains (approximately 16−18kD16-18 kD).
  • Myosin head is the site of ATPase enzyme activity.
Heavy Chain Subcomponents:
  • Light meromyosin: Connects the other light meromyosin to form the tail region.
  • Heavy meromyosin: Contains binding sites for both actin and ATP.
Myosin Heavy Chain Isoforms:
  • Slow Isoforms:
    • Myosin heavy chain one beta.
    • Cardiac muscle: myosin heavy chain type one alpha.
  • Fast isoforms:
    • Myosin heavy chain 2B (more recently referred to as 2X).
    • Hybrids: type 2D2X and myosin heavy chain 2A.
  • Most resistance training populations see a migration towards type 2A.
  • Myosin heavy chain isoforms relate to specific types of motor units.

Myosin Light Chain

  • Most muscle contains two pairs of light chains.
Types:
  • Essential light chains: light chain one and light chain three.
  • Regulatory: light chain two.
Function:
  • Combination of light chains and myosin heavy chain modulate the contractile response.
  • Enhance myosin-actin interactions during contraction.
  • May play a role in post-activation potentiation (PAP).
Post Activation Potentiation (PAP):
  • True PAP: Physiological mechanisms that may last tens of seconds.
  • Post Activation Performance Enhancement (PAPE): Tangible outcomes in performance lasting several minutes after activity.

M Line (M Band) Proteins

  • Myomesin: Binds directly to titin and heavy chains of myosin.
    • May act as an elastic cross-link connecting titin at the M line with the myosin filaments.
  • M protein: Binds to titin and myosin.
    • Present only in fast-twitch muscle fibers.
  • Myosin-binding protein C: Binds to myosin.
    • Plays a critical role in maintaining thick filament structure.
    • Helps regulate contraction by controlling cross-bridge formation and cycling.
  • Muscle-type creatine kinase isoform (MMCK): Small amount (5-10% depending on fiber type) is bound to the M line/disc.
    • Functionally coupled to myofibrillar actin-activated magnesium ATPase as an efficient intramyofibrillar ATP regenerator.
    • Helps maintain ATP quantity at the myosin head for crossbridge cycling and contraction.
  • Muscle ring finger one (MRF1) proteins:
    • Localized to the Z disc/line and the M line lattice of myofibrils.
    • Relates to the degradation of myofibrils and the turnover of contractile apparatus.
    • Vital to the structure and function of healthy muscle.

Titin (Connectin)

  • Most abundant muscle protein.
  • Large protein extending from the Z line to the M line.
Isoforms:
  • T1 (alpha-connectin): Associated with higher force production capacity and tends to be less stiff.
  • T2 (beta-connectin): Tends to have greater stiffness than T1.
Role in Force Regulation:
  • Considered almost as a myofilament above just actinomycin.
  • Plays an active role in force regulation, especially when muscle fibers are stretched actively to long lengths.
  • Proposed to serve as a molecular blueprint, helping specify and coordinate the assembly of structural, regulatory, and contractile proteins of the sarcomere.
  • Serves as a molecular spring, giving striated muscle integrity during contraction, relaxation, and stretch.

Obscurin and Novex-Three

  • Titin binds to Obscurin. Novex3 is a splice variant of titin that extends from the Z disk to Obscurin.
  • Functional significance of interaction between Obscurin, Titan, and Novex3 remains speculative.
  • May be related to sarcomere restructuring.

Z Line

Desmin:
  • Forms a connection between adjacent Z lines from different myofibrils.
  • Helps keep the sarcomere in good register.
  • Partially responsible for the striated appearance of muscle.
Alpha Actinin:
  • Holds the thin filament in place and keeps it in good register.
  • Z lines of slow fibers have more alpha actinin.

Three-Filament Model

  • Old contractile model: actin + myosin.
  • Newer model: actin + myosin + titin.
Titin's Role:
  • Provides stability to the sarcomere.
  • Centers the myosin filament in the middle of the sarcomere.
  • Provides increasing force as the muscle stretches.
  • Prevents overstretching and damage to the sarcomeres.
  • Provides little resistance and easy extensibility of the muscles in a passive state.
  • Resists active stretching.
  • Provides an energetically cheap force during eccentric muscle contractions.