Introduction

To move our bodies and the substances inside them, we have evolved three types of tissue: skeletal, cardiac, and smooth muscle. These tissues can contract, which enable mechanical work to be done by the body. The significance in having multiple types of muscle tissue lies in their unique capabilities and functions. Skeletal, cardiac, and smooth muscle are responsible for voluntary movement, the pumping of blood, and involuntary contractions, respectively. By understanding these three characteristics of muscle—structure, mechanism, and disease—we can gain a better view of how they coordinate critical processes in the body.

The Structure of Muscle Tissue

The sarcomere is made up of highly organized filaments. When these sarcomeres are combined into myofibrils and eventually muscle fibres, it gives the muscle a striated appearance. Hence, skeletal muscle can be identified through the presence of multi-nucleated, striated fibres (MZ’s Lecture Slides).

Unlike skeletal muscle, cardiac muscle is usually binucleated or mononucleated. This is feasible as less protein is required in these smaller cells. These cells are found within the heart, where they must follow highly precise contraction patterns for the proper pumping of blood. To achieve this, cardiac muscle cells are electrically connected through intercalated discs. These discs contain gap junctions and connections for rapid dissemination of signals. Fascia adherens and desmosomes, required to keep cells together during contraction, are also found here (Koeppen and Stanton, 2017). Despite these differences, cardiac muscle still uses the sarcomere as its basic unit of contraction. Although there are slight differences, which will be discussed later in this essay, the overall mechanism remains very similar.

The same cannot be said for smooth muscle, however. Instead of an organized structure like the sarcomere, smooth muscle has multi-directional contraction through disorganized filaments. These filaments are still made of actin and myosin, but they do not run in the same direction. For this reason, smooth muscle does not have a striated appearance. Smooth muscle cells can also be electrically connected like cardiac muscle, as found in single-unit smooth muscle. However, they can also act separately, where it is classified as multi-unit (MZ’s Lecture Slides; Koeppen and Stanton, 2017).

Contractile Mechanisms

Despite the structures of each muscle being different, the overarching mechanism for contraction is somewhat similar. In short, a signal induces an increase in intracellular calcium concentrations. This leads to the troponin-tropomyosin complex changing conformation, allowing the myosin heads to bind actin. Finally, this results in the sliding of the thick and thin filaments, leading to contraction. While this mechanism is conserved among muscle tissue, it is the slight differences which explain their functional specialisations (Koeppen and Stanton, 2017).

For example, each type of muscle is controlled by different nervous inputs. Skeletal muscle is controlled by α motor neurons from the central nervous system. These neurons branch out to innervate each muscle fibre, synapsing in an area termed the end plate. Once an action potential is received from the motor neuron, it will initiate an action potential in the skeletal muscle fibre (EM’s Lecture Slides). This signal travels along the sarcolemma, eventually reaching the T-tubule. The T-tubule is an invagination of the sarcolemma into the muscle fibre and is found between the A band and I band. It is surrounded by the sarcoplasmic reticulum (SR), which is the primary store of Ca²⁺ in the skeletal muscle fibres. Each T-tubule is associated with two terminal cisternae. This creates a junction called a triad. An AP triggers the activation of the L-type Ca²⁺ channels (LTCCs) in the membrane of the T-tubule. This results in a conformational change in the ryanodine receptor, which spans the gap between the T-tubule and the SR, releasing Ca²⁺ into the myoplasm (MZ’s Lecture Slides; Koeppen and Stanton, 2017).

This influx of Ca²⁺ is directly responsible for creating the twitch in muscle fibres. The first step of this process is the binding of Ca²⁺ to troponin C. This induces a conformational change in troponin T, which causes tropomyosin to move off the myosin binding sites in actin. This starts a four-stage cross-bridge cycle. At stage a, myosin partially hydrolyzes ATP. The muscle is still relaxed, as actin and myosin haven’t formed a cross-bridge yet. Once tropomyosin changes position, myosin forms a cross-bridge linkage at stage b. In stage c, ATP is fully hydrolyzed and causes a conformational change in myosin, pulling actin towards the M line. This shortens the sarcomere and achieves contraction. Finally, a new ATP molecule binds to myosin and the cross-bridge is released. If there is still high calcium, the cycle repeats (Koeppen and Stanton, 2017).

This process is almost identical in cardiac muscle, with subtle adaptations. The first of these adaptations is the cardiac action potential (AP). Unlike regular APs, cardiac muscle requires identical contractions for proper pumping. To achieve this, the cardiac AP is prolonged to ensure that the contractile machinery is reset before another AP is fired. Once an AP is fired, it travels along the sarcolemma and reaches the T-tubule. Instead of a triad, cardiac tissue has a diad; each T tubule is only associated with one terminal cisterna of the SR. Furthermore, cardiac muscle requires extracellular Ca²⁺ to enter through LTCCs and induce calcium release from the SR. By contrast, skeletal muscle only requires Ca²⁺ from the SR. After this, the mechanism for contraction is the same—Ca²⁺ binds troponin C and initiates the cross-bridge cycle. The force produced can vary in the heart, as the sarcomeres are not at their optimal length for contraction normally. This can be changed with more stretch, producing more force as the sarcomeres can contract more. This is termed Starling’s Law of the Heart (MZ’s Lecture Slides).

Contraction within smooth muscle varies significantly from the other types of muscle tissue, primarily due to its lack of sarcomeres. Instead, the filaments are connected to dense bodies throughout the cell in an unorganized fashion. Initiation of contraction is also different in smooth muscle. In response to signaling from a neuron, hormone, or other factor, smooth muscle cells will release Ca²⁺ from the SR. This is facilitated by the caveolae. Ca²⁺ enters through these pockets and causes more calcium to be released via the SR. Ca²⁺ then binds to calmodulin, which activates the myosin light chain kinase (MLCK). MLCK phosphorylates the myosin light chain, enabling it to bind to actin and cause contraction (Koeppen and Stanton, 2017).

While skeletal muscle and cardiac muscle relax by rapidly sequestering Ca²⁺ through pumps such as SERCA, smooth muscle cells rely on the myosin light chain phosphatase (MLCP) to inactivate myosin. Along with the slow pumping of Ca²⁺, the low activity of MLCK and MLCP enables the long, energy-efficient contractions of smooth muscle tissue. This is known as the latch mechanism. It is important in muscles that are almost always contracted, as it saves energy for the organism (MZ’s Lecture Slides; Koeppen and Stanton, 2017).

Diseases in Muscle Tissue

In complex processes such as muscular contraction, small changes can have drastic consequences. These effects can be seen through diseases, with some appearing more commonly than others. For example, the most common disease associated with muscle tissue is muscular dystrophy. This disease is caused by mutations in the dystrophin protein, which is critical for maintaining the structure of the sarcolemma during contraction. It protects the membrane from tearing. Dystrophin is mainly found within cardiac and skeletal muscle, which means mutations in the protein lead to deterioration of muscles across the body and in the heart (Koeppen and Stanton, 2017).

While diseases in smooth muscle tissue are less defined, they are still very prevalent. One of the biggest diseases associated with smooth muscle is asthma. Asthma can be triggered by many factors, but all of them act on smooth muscle by causing it to constrict the airways. This makes it harder for a person to breathe. As the disease progresses, the smooth muscle can change structure; it can become more voluminous and thicker, further restricting the passage of air into the lungs (Xiong et al., 2022). While the cause of these effects has not been elucidated down to a molecular level, our knowledge of smooth muscle structure has helped us understand the disease and how it progresses.

Conclusion

By understanding how muscles are built from the bottom up, it is easy to see how crucial they are for bodily function. It is only by looking at the molecular mechanisms involved in muscle contraction that we can begin to understand how our body is able to perform its most complex mechanical tasks. Furthermore, we can understand mechanistically how diseases affect our body, and what steps can be taken to reduce their effects. However, it is important to remember that our knowledge of these complex pathways are the results of hundreds of experiments, with more being done every day to uncover more about our complex machinery.

References

Koeppen, Bruce M, and Bruce A Stanton. Berne and Levy Physiology. 7th ed., Saintt Louis Elsevier Health Sciences, 2017.

Xiong, Dora (Jun Ping), et al. “Airway Smooth Muscle Function in Asthma.” Frontiers in Physiology, vol. 13, 5 Oct. 2022, p. 993406, www.ncbi.nlm.nih.gov/pmc/articles/PMC9581182/, https://doi.org/10.3389/fphys.2022.993406.

Professor Manuela Zaccolo’s Lecture Slides

Professor Edward Mann’s Lecture Slides