Recall that when a muscle fiber (cell) is electrically activated (i.e., excited) at the neuromuscular junction, this excitation results in the release of Ca²⁺ released by the sarcoplasmic reticulum (SR). The Ca²⁺ released by the sarcoplasmic reticulum (SR) initiates a repetitive series of events called the muscle contraction cycle which leads to the shortening of a muscle.
Muscle Contraction Cycle - (a) A resting muscle fiber. (b) Calcium is released from the sarcoplasmic reticulum and binds to troponin; the troponin-tropomyosin complex shifts to reveal the myosin binding site on actin. (c) A crossbridge is formed as myosin binds to actin. (d) A power stroke occurs as the myosin neck (hinge) bends, shortening the sarcomere. ADP and inorganic phosphate (Pi) are released. (e) ATP binds the myosin head causing the release of the crossbridge. Cleavage of ATP to ADP and Pi causes the myosin head to recock. This cycle continues so long as calcium is still available. When calcium is no longer available, cross bridges will not reform and the sarcomere and muscle fiber relax.
Recall that the proteins that form thin and thick filaments contain four key binding sites:
Calcium-binding site on troponin.
Myosin-binding site on actin.
Actin-binding site on the myosin head.
ATP-binding site on the myosin head.
When a muscle is at rest, the tropomyosin in a thin filament covers the myosin binding site on actin, keeping the thin and thick filaments from interacting. When Ca²⁺ ions are released from the SR, they bind to the calcium-binding site on troponin which shifts tropomyosin away from its position, revealing the myosin-binding site on actin. Once this binding site is available, a myosin head binds to it, forming what is called a crossbridge. The neck (hinge) region of myosin then decreases its angle, pulling on actin. This action is called a power stroke and it causes the sarcomere to shorten approximately 10 nm (nanometers) which is 1/500,000th of the thickness of a sheet of paper. The power stroke causes the ADP and inorganic phosphate (Pi) to be released, leaving an open ATP-binding site. When a new molecule of ATP binds, the crossbridge between myosin and actin is released. ATP is then cleaved to become ADP and Pi, releasing energy that is used to recock myosin, moving the myosin head back to its original position.
As summarized in the image below, the electrochemical signal from a motor neuron causes the excitation of a muscle fiber which results in the contraction of a muscle fiber. If enough muscle fibers contract within a muscle, sufficient tension can be produced to cause the muscle to shorten.
Contraction of a Muscle Fiber - A cross-bridge forms between actin and the myosin heads triggering contraction. As long as Ca²⁺ ions remain in the sarcoplasm to bind to troponin and as long as ATP is available, the muscle fiber will continue to shorten.
This series of events will continue to cycle so long as Ca²⁺ ions and ATP remain available or until the muscle reaches its anatomical limit. Note that each thick filament of roughly 300 myosin molecules has multiple myosin heads, and many cross-bridges form and break continuously during muscle contraction. Multiply this by all of the sarcomeres in one myofibril, all the myofibrils in one muscle fiber, and all of the muscle fibers in one skeletal muscle, so you can understand why so much energy (ATP) is needed to keep skeletal muscles working. In fact, it is the loss of ATP that results in the rigor mortis observed soon after someone dies. With no further ATP production possible, there is no ATP available for myosin heads to detach from the actin-binding sites, so the cross-bridges stay in place, causing rigidity in the skeletal muscles.
When the body relaxes a skeletal muscle, all of the events that led to a muscle contraction reverse.
Electrochemicals in the motor neuron stop being generated.
ACh is no longer released into the neuromuscular junction (NMJ) and any remaining ACh is broken down by acetylcholinesterase.
The muscle fiber is no longer excited and is able to repolarize or alter its membrane potential to become more negative.
The lack of depolarization stops the release of Ca²⁺ from the SR. The SR is instead able to actively pump Ca²⁺ back in, removing it from the sarcoplasm.
The lack of available calcium forces the troponin-tropomyosin complex to shift, covering and blocking the myosin-binding site on actin. This restricts any cross bridges from being formed.
Sarcomeres relax and muscle fibers will lengthen causing the muscle to lengthen.
Relaxation of a Muscle Fiber - Ca²⁺ ions are pumped back into the SR, which causes the tropomyosin to reshield the binding sites on the actin strands. A muscle may also stop contracting when it runs out of ATP and becomes fatigued.
watch
Please watch the following video for more information on this topic.
IN CONTEXT Disorders of the Muscular System
Duchenne muscular dystrophy (DMD) is a progressive weakening of the skeletal muscles. It is one of several diseases collectively referred to as “muscular dystrophy.” DMD is caused by a lack of the protein dystrophin, which helps the thin filaments of myofibrils bind to the sarcolemma. Without sufficient dystrophin, muscle contractions cause the sarcolemma to tear, causing an influx of Ca²⁺, leading to cellular damage and muscle fiber degradation. Over time, as muscle damage accumulates, muscle mass is lost, and greater functional impairments develop.
DMD is an inherited disorder caused by an abnormal X-chromosome. It primarily affects males, and it is usually diagnosed in early childhood. DMD usually first appears as difficulty with balance and motion and then progresses to an inability to walk. It continues progressing upward in the body from the lower extremities to the upper body, affecting the muscles responsible for breathing and circulation. It ultimately causes death due to respiratory failure, and those afflicted do not usually live past their 20s.
Because DMD is caused by a mutation in the gene that codes for dystrophin, it was thought that introducing healthy myoblasts into patients might be an effective treatment. Myoblasts are the embryonic cells responsible for muscle development, and ideally, they would carry healthy genes that could produce the dystrophin needed for normal muscle contraction. This approach has been largely unsuccessful in humans. A recent approach has involved attempting to boost the muscle’s production of utrophin, a protein similar to dystrophin that may be able to assume the role of dystrophin and prevent cellular damage from occurring.
make the connection
If you're taking the Anatomy & Physiology I Lab course simultaneously with this lecture, it's a good time to try the Lab Muscle tissues: An Overview in Unit 4 of the Lab course. Review the lab-to-lecture crosswalk if you need more information. Good luck!
terms to know
Muscle Contraction Cycle
A repetitive series of events which lead to the shortening of a muscle.
Crossbridge
A bond between a myosin head and an actin subunit.
Powerstroke
The action of myosin pulling on actin, resulting in the shortening of the sarcomere.
summary
In this lesson, you learned the molecular steps of the muscle contraction cycle. You learned how the various components of the myofilaments interact with one another to cause the shortening or lengthening of a muscle. This interaction facilitates the mechanism of the sliding filament model.
