At which stage of the contraction cycle do the myosin heads bind ATP?

The contraction of skeletal muscle is powered by the interaction of two key proteins – actin and myosin. These proteins slide past each other, generating force and shortening the muscle. This process requires energy, which is provided by ATP (adenosine triphosphate). The cycling of myosin binding and hydrolyzing ATP is crucial for muscle contraction. So at which stage of the muscle contraction cycle do the myosin heads bind ATP?

The Contraction Cycle

Muscle contraction occurs in a cyclical process involving the following key stages:


In the relaxed state, the myosin heads are not bound to actin. ATP is bound to the myosin heads, keeping them in a cocked position ready to bind to actin.

Cross-bridge Formation

The myosin heads bind to specific binding sites on the actin filament, forming cross-bridges. This causes the myosin heads to change conformation, pulling the actin filaments towards the center of the sarcomere and muscle contraction begins.

Power Stroke

The myosin head undergoes a power stroke, caused by the release of phosphate from the ATP molecule. This provides the power for pulling the actin filament.

Cross-bridge Detachment

ATP binds to the myosin head, causing it to detach from actin. The cross-bridge is broken, allowing the myosin head to recoil back to its cocked position, ready for the next cycle.

So clearly, it is during the cross-bridge detachment stage that the myosin heads bind ATP and release from actin. The binding of ATP causes the myosin head to detach, ending the power stroke.

The Role of ATP in Muscle Contraction

Let’s look closer at the role of ATP in muscle contraction:

ATP Provides the Energy

The energy for muscle contraction ultimately comes from the breakdown of ATP. ATP is hydrolyzed into ADP + phosphate, releasing energy. This energy powers the contraction of the sarcomere unit and the sliding of the myofilaments.

ATP Binding Causes Cross-Bridge Detachment

As described, when ATP binds to the myosin head, it causes the dissociation of myosin from actin, breaking the cross-bridge. This detachment ends the power stroke and allows the myosin to recoil back, ready for the next contraction cycle.

ATP must be Replenished

The amount of ATP stored in muscles is only sufficient for a few seconds of contraction. For sustained muscle activity, ATP must therefore be continuously regenerated from ADP + phosphate, via cellular respiration. The breakdown and resynthesis of ATP power the sustained cyclic interactions between myosin and actin.

The Molecular Mechanism of Myosin-Actin Binding

The molecular events underlying the cross-bridge cycle are complex. Let’s break it down step-by-step:

Step 1 – ATP Hydrolysis

Myosin has an ATP binding site that catalyzes ATP hydrolysis. When ATP initially binds, the myosin head is in the cocked position. Hydrolysis of ATP into ADP + phosphate causes a conformational change in the myosin, priming the head for actin binding.

Step 2 – Cross-Bridge Formation

The myosin head strongly binds to actin, forming the cross-bridge. The release of phosphate causes the power stroke, sliding the actin and myosin filaments past each other.

Step 3 – ATP Binding

New ATP rapidly binds to the actin-attached myosin head. This causes myosin to change conformation, lowering its actin affinity and detaching the cross-bridge.

Step 4 – Cocked Position

The myosin head then hydrolyzes the newly bound ATP, which re-cocks it ready for the next power stroke.

The Importance of Timing

The precise timing of ATP binding to the myosin head is critical for optimal muscle contraction:

  • ATP must bind quickly after the power stroke to allow rapid cycling.
  • However, ATP shouldn’t bind too quickly or the power stroke will be cut short.
  • The rate of ATP diffusion to the myosin head must be precisely regulated to match the contraction speed.
  • ATP binding and cross-bridge detachment ends the power stroke, but it also prepares myosin for the next contraction cycle.
  • This exquisite coordination ensures rapid yet sustained muscle contraction.

Rigor Mortis and ATP Depletion

If ATP is completely depleted after death, myosin and actin remain tightly bound together in a state called rigor mortis. The lack of ATP prevents cross-bridge detachment, causing stiffening of the muscles.

This demonstrates the vital role ATP plays in dissociating myosin from actin and ending the contraction cycle. Without ATP, the myosin heads remain firmly attached to actin in a contracted position.

Energy Systems for ATP Regeneration

During exercise, the body relies on different energy systems to continuously regenerate ATP:

Phosphocreatine System

Stores of phosphocreatine donate phosphate to rapidly replenish ATP in the first few seconds of exercise.


Breaks down glucose without oxygen to generate ATP at a fast rate for up to around 2 minutes.

Oxidative Phosphorylation

Uses oxygen to generate the most ATP from glucose and fat oxidation. Supports lower intensity long-duration exercise.

By utilizing these different energy systems in the right balance, muscles can maintain the rapid ATP turnover required for exercise ranging from a few seconds up to hours.

Actin-Myosin Binding in Smooth and Cardiac Muscle

The cross-bridge cycle also operates in smooth muscle (e.g. intestines, uterus) and cardiac muscle of the heart. However, there are some key differences:

Smooth Muscle

  • No troponin complex – Calcium binds directly to calmodulin
  • Cross-bridge cycling is slower with a latch-bridge mechanism
  • Phosphorylation of myosin light chains regulates contraction

Cardiac Muscle

  • Troponin C binds calcium to initiate contraction
  • More mitochondria allow higher oxidative capacity
  • Intercalated discs connect cardiac muscle cells

Despite these differences, ATP binding and hydrolysis remains central to cross-bridge cycling and contraction in these muscle types.

Comparative Cross-Bridge Cycling Rates

The speed of cross-bridge cycling differs between muscle fiber types:

Muscle Fiber Type Contraction Speed
Fast twitch (type II) Fast cycling – 120 ms per cycle
Slow twitch (type I) Slow cycling – 200 ms per cycle

Fast twitch muscle fibers have faster ATP turnover and cross-bridge cycling. This allows faster shortening velocities and high power output, albeit with faster fatigue.

In contrast, slow twitch fibers have slower cycling rates better suited for endurance exercise.

Effects of Resistance Training

Resistance exercise training induces adaptations in the proteins involved in cross-bridge cycling and contraction:

  • Increased myosin heavy chain synthesis – More myosin heads
  • Upregulated calcium signaling – Enhances activation
  • Improved ATPase activity – Faster cross-bridge cycling
  • Mitochondrial proliferation – Enhances ATP regeneration

Together these changes increase contractile strength and power output. It also allows more rapid repetitive cross-bridge cycling during intense muscle contractions.


During the cross-bridge cycle, myosin binds ATP and detaches from actin during the detachment phase, which ends the power stroke.

The energy from ATP hydrolysis allows myosin to repeatedly bind and pull on actin filaments, sliding the myofilaments past each other to generate contraction.

By rapidly diffusing to the myosin head, ATP maintains cyclic actin-myosin interactions and muscle contraction. Without ATP, contraction would halt as the cross-bridges become locked in rigor mortis.

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