The Biochemistry of Muscular Contraction – Myosin, Actin, Troponin
Like dyneins and kinesins, myosin proteins use energy from the hydrolysis of ATP to move along microfilaments (also known as actin filaments). Myosin proteins form aggregations called thick filaments which slide over each other to produce muscular contraction.
Each thick filament is associated with thin actin strands and troponin and tropomyosin proteins that block myosin binding to them at rest. This is known as the sliding filament model.
Biochemistry of Muscle Contracture
Action of Myosin in Muscular Contraction
Myosin is an enzyme that converts chemical energy from adenosine triphosphate (ATP) into mechanical energy. It moves along actin filaments, also called microfilaments, to produce muscle contraction. This movement is referred to as the sliding filament model of muscle contraction, and it relies on the interaction between myosin and actin. Myosin is a multi-subunit protein that forms part of the sarcomere, a group of proteins responsible for shortening the length of muscle fibers. It is also an important component of the myofibril, a structural unit of muscle cell that creates the force that produces muscle contractions.
Skeletal muscle myosin was the first myosin protein to be identified, and it is a member of the myosin superfamily of ATPases that binds to and moves along actin filaments. These macromolecular proteins are found in striated muscle and other types of smooth and cardiac muscle tissue, and they form the contractile units of skeletal muscles known as muscle fibers.
Each myosin molecule has a head domain, neck domain, and tail domain. The neck domain acts as a linker that connects the head domain to the actin filament and enables the molecule to generate force. Myosin’s catalytic motor domain uses ATP hydrolysis to move its binding site along the actin filament, or microfilament. The resulting movement is similar to the way that a bicycle wheel turns. The velocity of the myosin molecule depends on the rate of passing through a complete kinetic cycle of binding ATP, binding ADP, and hydrolyzing ATP.
Multiple myosin molecules generate the force that causes muscles to contract through a power stroke mechanism that is fuelled by the energy released from ATP hydrolysis. The ATP hydrolysis causes myosin to bind to the actin filament and pull against it, causing the filament to slide past each other. This process is repeated over and over to cause the muscle to contract.
In skeletal muscle cells, myosin and actin form thick filaments that are the primary components of myofibrils. These filaments are responsible for the force that makes muscles contract. The contraction of a muscle can be described by its length or tension, or both. A muscle can be contracted to change its length or its tension, but not both at the same time.
Action of Actin in Muscular Contraction
Actin is a protein found in eukaryotic cells that forms thin filaments and plays an important role in muscle contraction. It also plays a crucial role in cell movement and other cellular functions. Actin monomers polymerize to form actin filaments, which consist of two helixes twisting around each other. They are polarized, meaning that the affinity for addition of new actin monomers at each end is different. This can lead to a buildup of actin filaments at one end while the opposite end depolymerizes. This phenomenon is known as treadmilling. The polarization of actin monomers is caused by the presence of a molecule of ATP binding to each of them. This binding is essential for the reversible process of filament formation, and it occurs only at specific concentrations.
The helixes of the actin filament are anchored by proteins such as gelsolin and profilin, which form bridges between adjacent strands of actin. ATP binding to actin alters the conformation of the actin helix, and these changes in conformation can cause the bridges to shift back and forth between weak-binding and strong-binding conformations. This oscillation in the binding site allows ATP to hydrolyze and release energy. This energizes the actin, which then binds to myosin.
A triad of myosin, actin, and troponin is found in each sarcomere of skeletal muscle. As the muscle is stretched or shortened, the myosin filament slides into the H-zone of the actin filament. As the H-zone moves into position, it creates a force against lengthening and causes the muscle to generate maximum active tension at an ideal length. Once the muscle has reached this ideal length, however, active tension begins to decrease.
The actin filament in the H-zone is a major contributor to this passive tension, and it consists of G-actin and F-actin. G-actin is monomeric and globular, while F-actin is a fibrous protein that forms the contractile apparatus of a muscle cell. There are several isoforms of actin, including a-skeletal and a-cardiac actin. There are also b-cyto and g-cyto isoforms of actin, which are mainly expressed in non-muscle cells.
Action of Troponin in Muscular Contraction
Troponin is a protein involved in muscular contraction in the heart muscle cells. During a heart attack, spills into the bloodstream. It’s a biomarker, meaning it shows that heart tissue has been injured. This is why a high-sensitivity cardiac troponin test (hs-cTnT) has become the gold standard in diagnosing heart attacks. It can detect damage to the heart muscle much earlier than conventional creatine kinase MB (CK-MB) tests, which are used in combination with an EKG or echocardiogram.
Troponins are specific for striated muscles and bind to the calcium channel in muscle cells, changing its conformation and allowing it to open. This signals the activation of myosin binding sites, causing muscle contraction. The skeletal muscle troponin I (TnI) has a stronger inhibitory effect on actomyosin ATPase than the cardiac troponin T (TnT).
Elevated levels of troponin I or T in the blood are a strong sign of heart disease and can only be seen if there is damage to the heart muscle. In addition to a heart attack, troponin elevations can also be caused by other stresses on the heart such as severe sepsis or very high blood pressure that can cause heart failure. Other systemic illnesses such as kidney failure, pulmonary embolism and myocarditis can also result in elevated troponin levels.
In a cTnT test, the patient is connected to a monitor in the emergency room or doctor’s office and a band will be placed around the arm just above the vein that will be punctured for the sample. The blood will be collected into a tube, which is then sent to the laboratory.
The lab will then run a test that looks for the presence of cTnI or cTnT in the blood. A normal level is less than 0.1 mg/dL. Troponin testing is performed using monoclonal antibodies that are highly specific for cTnI and T. Other proteins, such as CK-MB or total creatine kinase, are not detected by these tests. These tests can be performed in most hospitals and are able to detect myocardial injury within four hours after an event. cTnI and cTnT are measured in serum, so the results can be compared between laboratories.
Action of Calcium in Muscular Contraction
Calcium is an alkaline earth metal that is a component of the skeletal and cardiac muscles. It is found in food and in dietary supplements. The body uses calcium to form and maintain bones, for nerve transmission, and to balance other nutrients, such as magnesium, potassium, and phosphorus. It also regulates the movement of the ribosome, which synthesizes proteins. The body also uses it to regulate blood pressure, blood clotting, and calcification of soft tissues.
Skeletal muscle contraction occurs when the central nervous system sends a signal to contract a particular muscle. This signals are transmitted through a synapse called the neuromuscular junction, which is a membrane that separates two motor neurons. A molecular signal that is carried by the action potential depolarizes the membrane of a motoneuron, and causes voltage-gated calcium (Ca2+) channels to open in the presynaptic cell. This results in a rise in cytosolic Ca2+, which triggers the release of the neurotransmitter acetylcholine. ACh binds to muscarinic acetylcholine receptors on the motor endplate of a muscle fiber, causing it to depolarize and initiate a sequence of events that result in the muscle fiber generating an action potential.
When the force of contraction exceeds the resistance against the muscle, a concentric contraction occurs. This causes the muscle to shorten and closes the distance between its origin and insertion. When the force of contraction is less than the resistance, the muscle lengthens, or produces an eccentric contraction.
During muscular contraction, the myosin head groups are tightly bound to actin in an intermediate configuration known as a flexed position or rigor complex. This is a state similar to what happens after death, when the muscle fibers run out of ATP. When the muscle is no longer generating electric activity, excess calcium is rapidly taken up by the sarcoplasmic reticulum and bound to troponin. This releases the myosin heads from actin, allowing them to bind to and activate a new set of microfilaments.
Calcium is a vital mineral for the human body, and the human diet contains a sufficient amount to ensure adequate intake. However, people who consume excessive amounts of calcium may be at risk for kidney stones and other health problems. The amount of calcium that the body can tolerate is based on many factors, including age and genetics. As you age, your body requires less and less calcium. Peak bone mass is usually achieved by the age of 30, and after that point, calcium is used for other bodily functions.
