›

Skeletal Muscle Contraction (Cross-Bridge Cycle)

Skeletal Muscle Contraction (Cross-Bridge Cycle)

Sections


Summary

Key Steps

  • ATP binds myosin, which causes its release from actin.
  • ATP hydrolysis causes the myosin head to rotate.
  • High energy myosin binds actin (forms the cross-bridge).
  • Phosphate release initiates the power stroke.

Myofibril internal histology

See: myofibril

Thick filaments

  • Form from myosin
  • The A band refers to the length of the thick filaments, "think "A" for d-a-rk – they are aniosotropic (or birefringent) in polarized light.
  • H Zone is a zone of only thick filaments.
  • M line bisects the A band.

Thin filaments

  • Form from actin
  • The I band is the region along the thin filaments (between the thick filaments).
  • Think "I" for L-i-ght – they are "isotropic" (do not alter polarized light).

Z disks

  • Transverse bands at the ends of the thin filaments.

Sarcomere

  • The contractile unit of the myofibril.
  • Comprises the area between the Z-disks.

Thin myofilament: Details

See: myofilament

  • The thin filament slides towards the H zone.
  • The (+) end attaches to the Z-disc sarcomere; the (-) end of the filament points toward the H zone.

Actin

  • Spherical molecules joined in pairs of strands (like beads on a string). It is referred to as F-actin for filamentous actin, and comprises a polymer of G-actin monomers that are arranged in a double helix.
  • There are myosin binding sites on actin and an ATPase site, an ATP-splitting site.

Tropomyosin

  • Threadlike strands

Troponin

  • Protein complexes that bind tropomyosin, actin, and also calcium (show their calcium-binding sites).

thick filaments: details

  • Comprise myosin molecules (technically myosin II), which form a golfclub shape, and comprise two heavy chains and two light chains.
  • The head forms from the heavy chain and contains the actin-binding site.

The "cross-bridge" is the bond between actin and myosin.

The Huxley Sliding-Filament Model

The rigor state.

  • The myosin head is bound to the thin filament.
  • Calcium is bound to troponin.
    • Calcium binding to troponin allows myosin access to its binding site on actin.

ATP induces release of actin.

  • Myosin has ATP bound to its head.
  • The actin molecules are separated from (no longer bound to) the myosin.
  • ATP is required to move out of the rigor state.
  • If ATP is absent, which occurs after death, rigor will persist, called rigor mortis.

ATP is hydrolyzed to ADP and Inorganic phosphate (Pi).

  • The myosin head rotates on the neck: it is now "cocked": it's in its high-energy state.
  • The "cocked" state causes the thin and thick filaments to again bind via their cross-bridge.
  • ADP and inorganic phosphate (Pi) are still bound to the myosin head.

Pi release initiates the power stroke for the myosin head to release its energy.

  • Accordingly, the thin filament begins its slide.

The myosin returns to its uncocked, low energy state.

  • At some point after the power stroke, ADP is released.
  • Note that this is an area of intertextual variation, some authors instead write that ADP is released at the same time as phosphate to initiated the power stroke.

ATP generation: 3 Key Means

Direct phosphorylation:

  • Creatine phosphate (a high-energy molecule stored in muscle cells) couples with ADP to make ATP and creatine.
  • Creatine kinase catalyzes the reaction.
  • As a corollary, creatine kinase is the best marker for muscle disease; it lies within muscle cells, for instance on the inner mitochondrial membrane, myofibrils, and sarcoplasm, and muscle injury releases it into the serum. Thus, muscle diseases are commonly associated with elevated creatine kinase levels.

Anaerobic glycolysis

See: glycolysis

  • Nets 2 ATP molecules.
  • Each glucose molecule is broken down into pyruvic acid molecules and ATP, but the pyruvic acid converts to lactic acid.
  • Strenuous anaerobic exercise results in lactate build-up, which causes pain.

Aerobic respiration (which occurs in the presence of oxygen)

  • Glucose is entirely broken down within the mitochondria to yield carbon dioxide, water, and large amounts of ATP.
  • As a corollary, we see that in the presence of oxygen, cells can maximize ATP production.

Reference Note:

  • We closely follow these steps as they are described in the 6th edition of Molecular Cell Biology, Chapter 17 – as numerous intertextual variations exist on this process.

Full-Length Text

  • Here we will learn the cross-bridge cycle: the Huxley sliding-filament model.
  • First, start a table so we can give a quick overview of key steps in the Huxley sliding filament model.
  • ATP binds myosin, which causes its release from actin.
  • ATP hydrolysis causes the myosin head to rotate.
  • High energy myosin binds ATP (forms the cross-bridge).
  • Phosphate release initiates the power stroke.

To begin, let's draw a sarcomere.

  • Draw a myofibril.
  • Then, draw a series of of short, thick filaments: the myosin, thick filaments.
  • Show that thin filaments interweave with them on both sides.
  • Now, at the ends of the thin filaments, draw transverse bands – the Z disks.
  • Indicate that a sarcomere, the contractile unit of the myofibril, comprises the area between the Z-disks;
  • Then, indicate that the A band refers to the length of the thick filaments, "think "A" for d-a-rk – they are aniosotropic (or birefringent) in polarized light.
  • Next, show that the H Zone comprises the region between the thin filaments, which only contain the thick filaments.
  • Show the M line, which bisects the A band.
  • Now, in order to show the I band, draw another sarcomere next to this one.
  • Show that the I band is the region along the thin filaments, between the thick filaments.
    • Think "I" for L-i-ght – they are "isotropic" (do not alter polarized light).
  • Elsewhere, we see that the repeating light and dark bands gives muscle fibers a striated appearance.
  • Now, let's focus in on key aspects of myofilaments.
  • Indicate that thin filaments notably comprise:
    • Actin, which are spherical molecules joined in pairs of double helical strands (like beads on a string),
    • Tropomyosin, which are threadlike strands, and
    • Troponin protein complexes that bind tropomyosin, actin, and also calcium (show their calcium-binding sites).
  • Next, indicate the myosin binding sites on actin.
    • There is also an ATPase site, an ATP-splitting site.
  • Next, show that thick filaments of myosin, which constitute heavy and light chains, form a golfclub shape, as such indicate their:
    • Head, neck, and tail.
    • Indicate the actin binding site on the head.
  • The "cross-bridge" is the bond between actin and myosin.
    • For directionality, show that filaments are polar: show that the (+) end attaches to the Z-disc sarcomere, whereas the (-) end of the filament points toward the H zone.
  • Show that, ultimately, the thin filament slides towards the H zone.

Now, let's draw key steps in the Huxley Sliding-Filament Model.

First, the Rigor state.

  • Draw a myosin head bound to the thin filament.
  • Specifically show calcium bound to troponin; in the excitation/contraction coupling tutorial, we learn the significance of this.
    • But in short: calcium binding to troponin allows myosin access to its binding site on actin.
  • Next, we see that ATP induces release of actin.
  • Redraw myosin with ATP bound to its head.
  • Then, draw the actin molecules as separated from (no longer bound to) the myosin.
    • Thus, we see that ATP is required to move out of the rigor state.
    • Write that if ATP is absent, which occurs after death, rigor will persist, called rigor mortis.
  • Next, show that ATP is hydrolyzed to ADP and Inorganic phosphate (Pi) prompts the myosin head to rotate on the neck: it is now "cocked" – it's in its high-energy state.
  • Now, show that the "cocked" state causes the thin and thick filaments to again bind via their cross-bridge.
  • Show that ADP and inorganic phosphate (Pi) are still bound to the myosin head.
  • Redraw this set-up but show that Pi release initiates the power stroke for the myosin head to release its energy.
  • Indicate that accordingly the thin filament begins its slide.
  • Finally, redraw the myosin in its uncocked, low energy state.
  • At some point after the power stroke, ADP is released.
    • Note that this is an area of intertextual variation, some authors instead write that ADP is released at the same time as phosphate to initiated the power stroke.
  • As we've seen, ATP is critical to muscle action, so let's quickly review 3 key ways in which ATP is generated and discuss some of their clinical consequences.

First, direct phosphorylation:

  • Indicate that creatine phosphate, which is a high-energy molecule stored in muscle cells, couples with ADP to make ATP and creatine.
  • Show that creatine kinase catalyzes the reaction.
  • As a corollary, creatine kinase is the best marker for muscle disease; it lies within muscle cells, for instance on the inner mitochondrial membrane, myofibrils, and sarcoplasm, and muscle injury releases it into the serum.
    • Thus, muscle diseases are commonly associated with elevated creatine kinase levels.

The second pathway, which is also fairly rapid is anaerobic glycolysis, which results in the net formation of a 2 ATP molecules.

  • To illustrate this pathway, indicate that each glucose molecule is broken down into pyruvic acid molecules and ATP, but show that the pyruvic acid converts to lactic acid.
  • As a corollary, indicate that strenuous anaerobic exercise results in lactate build-up, which causes pain.

Lastly, indicate that in aerobic respiration, which occurs in the presence of oxygen, glucose is entirely broken down within the mitochondria to yield carbon dioxide, water, and large amounts of ATP.

  • Thus, as a corollary, we see that in the presence of oxygen, cells can maximize ATP production.