Control of Muscle Contraction Part 2: ATP and the Cross Bridge Cycle

Control of Muscle Contraction Part 2: ATP and the Cross Bridge Cycle

1. Introduction

In previous tutorials in this module, we’ve established that

  1. Muscles contract when their sarcomeres shorten

    Diagram comparing a relaxed sarcomere (top) and a contracted sarcomere (bottom), with lettered structures. In both panels, thin (actin) filaments extend from Z discs at each end toward the center, while thick (myosin) filaments are located centrally. In the relaxed state, the Z discs are farther apart, the I bands (2) are wider, and a visible H zone (1) lies at the center of the A band (3). The M line (C) marks the midpoint of the sarcomere. In the contracted state, arrows indicate thin filaments sliding inward toward the M line, Z discs move closer together (D), the I bands shorten, and the H zone narrows or disappears, while the A band remains the same length.
    A relaxed sarcomere (top) and a contracted sarcomere (bottom). Click to see a labeled version.
  2. Sarcomere shortening occurs when nerve impulses stimulate muscle cells to release their stores of calcium ions (Ca++). This enables the heads of myosin molecules to attach to binding sites on actin. When the heads pull back — it’s called a power stroke — the sarcomere shortens as the Z lines draw together.

    Three-panel diagram illustrating how calcium enables muscle contraction at the molecular level. In panel 1 (relaxed muscle), the thin filament (actin) is shown with tropomyosin covering the myosin-binding sites, while troponin is attached to tropomyosin. A myosin head containing ADP is positioned near the thin filament but cannot bind. In panel 2, calcium ions (Ca²⁺) bind to troponin, causing tropomyosin to shift and expose the myosin-binding sites on actin. In panel 3, the myosin head binds to the exposed site and bends in a power stroke, pulling the thin filament toward the center of the sarcomere. Labels identify tropomyosin, troponin, myosin head, thick filament, thin filament, calcium ions, and the direction of filament movement.
    How calcium powers muscle contraction on a molecular level
    .

Understanding how sarcomere shortening is powered by ATP (and its counterpart, ADP and phosphate) will be the main topic of this tutorial But first, let’s review excitation-contraction coupling.

2. Excitation-Contraction Coupling: A Review

Lettered diagram illustrating excitation–contraction coupling at the neuromuscular junction and within a muscle fiber. At the top, a motor neuron axonal bulb (A) receives a nerve impulse (B). Synaptic vesicles (C) containing acetylcholine (D) fuse with the presynaptic membrane by exocytosis (E), releasing neurotransmitter into the synaptic cleft (F). Acetylcholine binds to receptors on the motor end plate (G), opening ligand-gated sodium channels (H) and allowing Na⁺ to enter the muscle fiber. This initiates an action potential (J) that travels along the sarcolemma (I) and down T-tubules (K). The action potential triggers calcium release (M) from the sarcoplasmic reticulum (L) into the sarcoplasm. Calcium binds to troponin (N), shifting tropomyosin (O) away from myosin-binding sites (P) on actin. This allows myosin heads (Q), carrying ADP and phosphate (R), to bind to actin and generate contraction.
Excitation-contraction coupling. Click to enlarge.

The diagram on the right shows how a nerve impulse gets transformed into a muscle contraction.

  1. Letter “A” represents the axonal terminal. At “B,” we see the nerve impulse — an action potential — traveling along the membrane of the axon as a wave of membrane depolarization. That action potential induces synaptic vesicles (“C”) filled with the neurotransmitter acetylcholine (“D”), to fuse with the axon’s cell membrane. Through exocytosis (“E”), the acetylcholine is released into the synaptic cleft (“F”), the fluid-filled space in between the axonal bulb and the motor end-plate (“G”): the specialized, folded membrane of the sarcolemma that lies opposite the axonal bulb.
  2. The acetylcholine diffuses across the synaptic cleft and binds with acetylcholine receptors (“H”) embedded in the motor end plate. These receptors are a part of gated membrane channels that open up in response to the binding of acetylcholine, allowing sodium ions — Na+ — to diffuse from the extracellular fluid into the sarcoplasm (“I”): the cytoplasm of the muscle fiber.
  3. If enough Na+ diffuses into the muscle fiber, a second action potential — this one happening in the muscle fiber— will start to move along the sarcolemma: this action potential is represented by “J”. This action potential will also move down into the T-tubules (“K”), indentations of the membrane that penetrate deeply into the sarcoplasm.
  4. In the sarcoplasm, the T-tubules connect to the sarcoplasmic reticulum (“L”).In the sarcoplasmic reticulum (SR), the action potential causes calcium ions (Ca2+, represented by “M”) to diffuse out of the SR and come into contact with the sarcomeres. The Ca2+ will bind with troponin (“N”), a protein that can adjust the position of tropomyosin (“O”), a long, fibrous protein.
  5. In relaxed muscle tissue, tropomyosin covers the actin-binding sites (“P”) on the thin filaments. But in response to Ca2+, the tropomyosin is nudged aside, The allows the myosin heads (“Q”) to bind with the myosin binding sites on actin.

Below, we’ll see how interactions between the myosin head and ADP and Phosphate (and ATP) generate the force that leads to sarcomere shortening. But first, a quiz.

3. Excitation-Contraction Coupling Quiz

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[h]Excitation-Contraction Coupling Diagram Quiz

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4. ATP, ADP, and the Cross-Bridge Cycle

Moving muscles during exercise is mechanical work. Work requires energy, and in cells, the molecule that powers work is ATP (adenosine triphosphate).

Diagram illustrating the ATP–ADP cycle. ATP, shown with three phosphate groups, releases energy for cellular work when one phosphate is removed, forming ADP plus inorganic phosphate (Pi). Energy input is then used to reattach the phosphate, regenerating ATP from ADP.
The ATP/ADP cycle

In relation to muscle contraction, here’s what you need to know about ATP.

  • ATP is the cell’s main energy-carrying molecule.
  • ATP and ADP are two forms of the same molecule, constantly being recycled in cells.
  • When ATP loses a phosphate and becomes ADP, energy is released that cells can use to do work. Above, the phosphate is shown by a circled letter “P”. In the discussion below, we’ll represent phosphate as Pi. The subscript “i” stands for inorganic (because the phosphate isn’t connected to any carbon atoms).

Here’s how ATP and ADP power muscle contraction. The diagram below shows a single myosin head interacting with an actin filament. In a real sarcomere, however, each thick filament contains hundreds of myosin heads, and each head can bind to actin. In addition, each sarcomere contains thousands of overlapping actin and myosin filaments, and each muscle fiber contains thousands of sarcomeres arranged end to end within each myofibril. When all of these interactions occur together, their combined effect is the large force produced by a contracting muscle.

Diagram illustrating the cross-bridge cycle in skeletal muscle contraction. A thin actin filament with troponin and tropomyosin lies above a thick myosin filament. In step 1, the myosin head is cocked with ADP and phosphate attached, while tropomyosin blocks actin-binding sites. In step 2, calcium ions bind to troponin, shifting tropomyosin and exposing actin-binding sites so a cross-bridge forms. In step 3, the myosin head releases ADP and phosphate and performs the power stroke, pulling actin toward the Z line. In step 4, ATP binds to myosin, causing it to detach from actin. In step 5, ATP is hydrolyzed to ADP and phosphate, re-cocking the myosin head and preparing it for another cycle.

  1. In diagram 1, we see a representation of myosin and actin in a relaxed sarcomere. The myosin head, which is bound to ADP and inorganic phosphate (Pi), is cocked and ready for action. However, it cannot bind to the thin filament because tropomyosin is blocking the actin-binding sites on actin.
  2. In diagram 2, calcium ions (Ca2+) appear on the scene. These calcium ions were released from the sarcoplasmic reticulum into the sarcoplasm. The Ca2+ binds to troponin, which causes tropomyosin to shift aside. This exposes the actin-binding sites on the thin filament, allowing the myosin head to form a temporary bond with actin. This bond is called a cross-bridge.
  3. Diagram 3 shows the power stroke. The myosin head releases inorganic phosphate (Pi), followed by ADP. This triggers a change in the shape of the myosin head, causing it to pivot and pull the actin filament toward the Z line. The combined action of millions of myosin heads pulling on actin filaments is the molecular basis of the force generated by muscle contraction.
  4. Diagram 4 shows ATP binding to the myosin head.
  5. Diagram 5 shows the effect of ATP binding: the myosin head detaches from the actin-binding site on the thin filament. The myosin head then hydrolyzes ATP to ADP and Pi using its ATPase activity (an ATPase is an enzyme that can break down ATP). This hydrolysis re-cocks the myosin head into its high-energy position, returning the system to the state shown in diagram 1.

If calcium continues to be released from the sarcoplasmic reticulum, this cycle will repeat, leading the muscle fiber to contract further. The process ends when:

  • The nerve impulse ends and calcium ions are actively pumped back into the sarcoplasmic reticulum.
  • ATP becomes unavailable (as in extreme fatigue or death, which leads to rigor mortis).

5. Quiz: The Cross Bridge Cycle

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[h]Excitation-Contraction Coupling Diagram Quiz

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This tutorial ends this module on muscle contraction.