Sliding filament model of muscle contraction

Definitions & Key takeaways

The sliding filament model of muscle contraction describes how muscles generate force and produce movement. Muscle contraction occurs as a result of the sliding of thin filaments (actin) over thick filaments (myosin) within muscle fibers.

The process of contraction starts when an action potential reaches the muscle fiber and triggers the release of calcium ions from the sarcoplasmic reticulum. The calcium ions bind to the protein troponin, which in turn causes a conformational change in tropomyosin, exposing the myosin binding sites on the actin filaments. Myosin heads then bind to the actin filaments and generate force. Attachment and detachment between actin and myosin occur several times during a single contraction.

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Introduction0:00–0:44

In order for a skeletal muscle to contract, your brain sends a signal, from an upper motor neuron down the spinal cord where it synapses with the cell bodies of lower motor neurons located in the anterior horn of the spinal cord.
From here, the signal travels through the lower motor neuron’s axon and until it reaches the axon terminal which is next to a muscle fiber.
At the site where an axon terminal meets the muscle fiber, called the neuromuscular junction, it releases small membrane-enclosed synaptic vesicles filled with acetylcholine.
Acetylcholine is a neurotransmitter that tells the muscle to contract. Now before we continue with the actual events that happen during the contraction, let’s focus on one muscle cell a myocyte and its functional units called sarcomeres.

Myocyte0:44–1:45

A myocyte is a long cylindrical cell with multiple nuclei located just below the sarcolemma, which is the cell membrane.
The sarcolemma is unique because it makes these tiny tunnels called T-tubules that project downwards from the surface towards the center of the muscle fiber.
The cytoplasm of a myocyte is called sarcoplasm, and the myocyte has a special type of smooth endoplasmic reticulum which is called sarcoplasmic reticulum.
The sarcoplasmic reticulum stores lots of calcium and runs parallel to the T tubules. Now, the sarcoplasm is filled with stacks of long filaments called myofibrils and each myofibril consists of contractile proteins and regulatory proteins.

Myosin and actin1:45–3:13

Contractile proteins include thick myosin and thin actin filaments. The thick myosin filament is made up of hundreds of myosin proteins, and each myosin protein has a tail and two myosin heads - it looks a bit like two golf clubs with their handles twisted around one another.
Multiple myosin proteins join their tails together to form the central part of the thick filament. In comparison, the thin actin filaments are made up of small, globular proteins called G-actin.
Each G-actin has an active site where the myosin head binds to it during contraction. These G-actin proteins forms a filament that looks like a long helix structure -- like a pearl necklace that’s gently twisted.
This entire filament is called F-actin. F-actin is associated with two regulatory proteins - tropomyosin and troponin.
Tropomyosin is a string-like protein that wraps around F-actin, covering its active sites so that the myosin heads can’t bind to it.
Troponin proteins are smaller and are made up of three subunits - there’s a T subunit that binds to tropomyosin, an I subunit that binds to F-actin, and a C subunit that binds to calcium ions.
Together, the F-actin, the troponin and tropomyosin make a complete thin filament. As it turns out, these thick and thin filaments don’t extend through the entire length of the myocyte, but instead, they’re arranged in short units called sarcomeres.

Sarcomeres3:13–5:15

When we look at sarcomeres with an electron microscope, the thick myosin filaments look dark, while the thin actin filaments look light which gives the muscle fiber a striped appearance.
Alright, now let’s zoom in and relate these bands to a structure of one sarcomere. At the center of the sarcomere is the M line made of myomesin proteins, where the thick filaments attach.
At the borders of the sarcomere are the two Z-discs made of alpha actin proteins, where the thin filaments attach. For every thick filament, there are two thin filaments-one above and one below and the two types of filaments overlap.
The region with only thin filaments is called the I band and it appears light. Each sarcomere unit has two half I bands at either ends.
The region with thick filaments is called an A band and it appears dark. Now most of the A band has overlap between the thick and thin filaments, but there’s an area towards the center called the H band where there are only thick filament, so it appears slightly lighter.
When the muscle contracts, the thick filaments pull the thin filaments above and below it towards the M line. The Z discs attached to the thin filament also gets pulled towards the M line, and the whole sarcomere gets shorter.
Now the A band does not change since it’s the length of the thick filament. But the H band and I band shorten because as the overlap increases, the regions that consists of only thick or thin filament decreases.
At maximal contraction, there’s an almost complete overlap of thick and thin filaments and the H band and I band are almost completely gone.

Muscle contraction5:15–6:18

So now let’s zoom in and look at how the myosin in the thick filament interact with the actin that makes up the thin filament.
When an action potential travels along the sarcolemma and reaches the T-tubule, it stimulates dihydropyridine receptors, or DHP receptors.
These receptors are interesting because they are physically connected to another receptor called the ryanodine receptor on the sarcoplasmic reticulum.
Once stimulated, the dihydropyridine receptor changes shape, and this causes the ryanodine receptor, which is a calcium channel, to open.
This allows the large quantities of calcium stored within the sarcoplasmic reticulum to flow out into the sarcoplasm. These calcium ions float over to the thin filaments and bind to the C subunits of the troponin regulatory proteins, which makes them change their shape.
When troponin changes shape, it moves tropomyosin out of the way, and that allows F actin to be bound by the myosin heads.
Now, before myosin can bind actin, it first needs to power up. Part of the myosin head is an ATPase, meaning that it can cleave an ATP molecule to ADP and phosphate ion and release some energy.

Cross-bridge formation6:18–7:38

The energy is used to cock the myosin head backwards, into its high energy position. It’s a bit like needing energy to crank back the arm of a catapult.
Next, the myosin head binds to the active site on the actin filament, and this is called cross-bridge formation. Cross-bridge formation is the trigger to release of the stored energy in the myosin head, kind of like firing the catapult.
When that happens, the myosin head launches towards the M line, pulling the thin filament along with it. This is called the power stroke.
The combined power strokes of all the myosin heads lead to sliding of the thin filament along the thick filament. Once the power stroke is done, the ADP and phosphate ion leave the myosin head, and a new ATP molecule is able to bind instead.
As soon as a new ATP is bound, the myosin head detaches from the active site. The new ATP is cleaved and the energy is used to re-cocking the myosin head to its high energy position for the next power stroke.
Now, once the signal sent from the lower motor neuron stops and the action potentials end, everything comes to a halt. That’s because calcium ions are pumped back into the sarcoplasmic reticulum by calcium pumps that use ATP.

Muscle relaxation7:38–8:11

When calcium fall, the C subunit of troponin is no longer bound to calcium, so the troponin returns to its original shape, and that allows tropomyosin to cover up the active sites on actin once more.
As a result, the myosin heads can no longer bind to actin, and the muscle relaxes. Alright, as a quick recap.

Review8:11–8:42

When an action potential reaches the T-tubule and stimulates small receptors, calcium ions are released from the sarcoplasmic reticulum into the sarcoplasm.
Calcium ions now bind to troponin C, what makes tropomyosin to slip down from active sites found on thin actin filaments, enabling thick myosin filament to form a cross-bridge with it.
This interaction causes myosin head to “power stroke” the actin filament towards the center of the sarcomere.