Molecular Mechanism of Skeletal Muscle Contraction

Every day, you wake up in the morning, you get out of bed, your skeletal muscles are at work!! You walk to the washroom, your skeletal muscle is at work!! You brush your teeth, your skeletal muscles are at work!! You try to lift something, your skeletal mus.....Okay you get the point!!!

But have you ever wondered what is happening at the molecular level that is making your skeletal muscles contract and allow you to make all the movements you're making!! No? Not even once? Okay.

Image Source

To understand the molecular mechanism of how our skeletal muscles contract, we should first briefly look at the structure and some important proteins that are present in the skeletal muscles.

image from BRS Physiology, 5th edition

Now that's a very, very detailed image with a lot happening on it. But all we need to know for today are some important proteins that make up these structures.

The thick filaments contain a protein called Myosin. The thin filament contains the proteins Actin, Tropomyosin and Troponin.

We also need to know that, when a muscle is contracting, it means the thick and thin filaments are going more into one another. Imagine you fingers interdigitating. When the fingers are going in, it's contraction and during relaxation the opposite is happening.

The interaction between Myosin, specifically myosin head and the Actin filament is what produces the mechanical motion, aka muscle contraction. Actin filaments have grooves to allow the myosin head to bind. But the Tropomyosin protein spirals around the actin in such a way that the grovves are covered and unexposed to the myosin heads. And the Troponin molecules are attached to the tropomyosin, doing nothing for the moment.

When an Action Potential reaches the muscle, and the specific Neurotransmitter binds to it's receptor on the muscle cell membrane, it causes depolarization of the muscle cell membrane, which eventually causes release of calcium ions from the sarcoplasmic reticulum. These Ca2+ ions bind to the calcium binding site on Troponin and this triggers a conformational change in the troponin in such a way that it kind of pulls the tropomyosin out of the way and the actin grooves are now exposed to the myoin heads for binding to it.

Note that during a contraction, at any given time, there will be hundreds of myosin heads attached to the actin filament. But just for the sake of simplicity, we'll deal with only one myosin head in this post.

image from BRS Physiology, 5th edition

Note the "+" and "-" signs on either ends of the actin filaments are just for indicating direction only. It has nothing to do with positive and negative charges.

To create the mechanical energy to cause the actual contraction, ATP is needed and the myosin can use the energy from ATP hydrolysis to kind of "crawl" along the actin filament causing muscle contraction.

The mysoin head has ATPase property which means it is able to hydrolyze ATP to tap into the energy and cause muscle contraction. When ATP binds to the myosin, it causes conformational change in myosin that results in the myosin head being released from the actin filament.

image from BRS Physiology, 5th edition

Recall that we mentioned, myosin head has ATPase property. So it will now hydrolyze the ATP to ADP and the energy released will be used to kind of load the myosin head into a high energy conformation. You can imaging it as sort of "cocking" up or loading a spring. Now this myosin head is ready for something called a power stroke.

Image Source

What this "cocking" up of the myosin head does is it moves the head towards the "+" end of the actin (recall from the pictiure, the head in it's attached position was slightly inclined towards the "-" side).

image from BRS Physiology, 5th edition

Notice that, now, there is no ATP present so the myosin head can bind back into the "next" groove of the actin filament. ("Next" groove because the position of the head has now changed due to to it getting cocked up. So say for example, at the start it was bound to groove number 1, now it will bind to groove number 2).

image from BRS Physiology

Now this is the power stroke or the force generating stroke. Now, why is binding of the myosin head to groove number two called the force generating or power stroke? Recall, at the starting, when there was no ATP bound, the myosin head was attached to groove 1 and was slightly inclined towards the "-" side of actin filament. Well, now, after binding to groove 2, ADP will be released, and in the same way when you release a cocked up spring it goes back to its original conformation, the myosin head will also incline back to the "-" side and this inclination will cause the actin filaments to move causing the thick and thin filaments to come closer together, and thus causing the contraction. Thus the name power/force generating stroke.

Looking at the whole cycle, also known as the cross bridge cycle at this point will give you guys the full picture of exactly what is happening with the actin and myosin!!

image from BRS Physiology, 5th edition

Now for the next cycle of contraction, the head will release from groove 2 and bind to groove 3 and contract the muscle more with the power stroke. Exactly how many cross bridge cycles will take place will depend on how much you wanted to contract you muscle. Remember skeletal muscles are under your voluntary control so you decide how much you wanna contract a specific muscle, for example, how much you wanna raise your arm will decide how many cross bridge cycles will take place to reach you desired position.

When the action potential stop, the released Ca2+ will be taken back into the sarcoplasmic reticulum and this means Ca2+ will no longer bind to the troponin which will result in the tropomyosin spiraling back around the actin filament and covering the grooved. Thus the myosin heads won't be able to bind and the muscle relaxes.

Next time you get out of bed, be thankful for you actin and myosin filaments!!

Sources :
BRS Physiology, 5th edition
Guyton and Hall textbook of Medical Physiology, Twelfth edition
Khanacademy

If you enjoy medical topics, or health tips, please make sure to follow me at @simplifylife

Peace!!