Myosin Smooth Muscle

Smooth muscle contraction occurs when calcium is present in the smooth muscle cell and binds onto calmodulin to activate myosin light chain kinase (Wilson et al., 2002). Phosphorylation of myosin light chains result in myosin ATPase activity thus cross-bridge cycling occurs causing the muscle to contract (Horowitz et al., 1996). There are two known models of excitation and contraction in smooth muscle, electromechanical coupling (EMC) and pharmomechanical coupling

Contractility of ASM requires an increased levels of intracellular Ca2+. When surface receptors are not activated, Ca2+ levels are low. Upon activation of these cell surface receptors by contractile agonists e.g. acetylcholine, serotonin and histamine, intracellular Ca2+ increases causing a contraction (9). Smooth muscle cell contraction is controlled by both receptor and mechanical activation of proteins actin and myosin and also changes to membrane potential.

Albuterol has affinity to β 2 receptors and binds to them, causing a relaxation effect. β2 receptors are members of the adrenergic family of receptors and therefore its effects are caused by an interaction with G proteins. β

Albuterol acts on beta2-adrenergic receptors located in the smooth muscle of respiratory tract. Activation of beta-2 receptors results in subsequent increase in adenyl cyclase and cyclic AMP. Increase in cyclic AMP leads to the activation of protein kinase A, inhibiting phosphorylation of myosin, thereby lowering intracellular ionic calcium concentrations, resulting in relaxation of the smooth muscle

The aim of this lab was to identify the significance of calcium’s role on the contraction of the smooth muscle (1 pg. 25).

Albuterol is a selective beta-2 adrenergic agonist, which means it specifically activates beta-2 adrenergic receptors on smooth muscle in the airways. How does this improve Mike’s asthma?

Albuterol action: Albuterol are effective bronchodilators because they have the ability to relax the airway smooth muscles. They carry out this effect by binding to active site beta2-adrenergic receptors on main receptors on bronchial smooth muscle relaxation with less cardiac stimulation. The onset of action starts in 20minutes and peak of action is between 2-3 hours, the half-life of 5 hours, metabolized in the liver, elimination is through renal excretion(80% to 100%) and less than 20% is detected in feces (Up To Date).

Multiunit smooth muscle highlights strands that are to some degree disorganized and occur as particular filaments as opposed to sheets. It can be found in the iris of the eyes and in the walls of veins. Multiunit smooth muscle tissue contracts when stimulation by motor nerve impulses. Visceral smooth muscle is made out of sheets of spindle-shaped cells in close contact with each other. This more common variety is found in the walls of hollow, visceral organs, for example, the stomach, digestion tracts, urinary bladder, and uterus. The filaments of visceral smooth muscles are equipped for stimulating one another. In this way, when one fiber is stimulated, the impulse might energize nearby strands that, thusly, might energize others. Visceral

This because when the myosin is heats up the first thing that is destroyed at the ATPase activity. The heavy-meromyosin fragment of the myosin would be destroyed (Stossel and Hartwig,1975).Thus meaning no enzymatic activity would not be able to take place and ATP will not be able attach and hydrolyzed .This would have the myosin be left attached to the actin. The higher the temperature the more the individual myosin heads produce a powerful power stroke thus increasing the contraction (Woledge et al, 1985). Because the number of heads that are attached myosin heads does not change with increasing temperature. The exertion per head is a part of the whole force with the sliding distance covered while in contact with the actin ( Woledge et al,

The actin-myosin interaction is most commonly known for its role in sliding filament theory, where myosin II bundles interact with actin filaments to shorten muscle sarcomeres and ultimately contract the muscle. However the myosin superfamily is huge, numbering 17 different proteins to date, and encompassing many different roles. The interaction of myosin and actin in non-muscle cells is thus a huge topic, but in understanding the structure, function and regulation of this part of the cytoskeleton, it is possible to find new drug targets and design new treatments to a huge number of diseases. One such target is the Rho-associated protein kinases (ROCKs), which are responsible for the regulation of the actin myosin cytoskeleton. This report aims to briefly cover the basic role of the actin-myosin cytoskeleton in non-muscle cells, how it is regulated by the ROCK family of serine/threonine kinases, and how ROCK inhibitors have could have huge therapeutic potential.

2. Figure 1 for Exercise 1, shows a positive linear tread, when stimulus intensity (V) increases the contractile force (N) also increases. As the stimulus intensity increases more motor units are recruited. To emphasize, when you have a stronger stimulus the more motor unit recruitment will get excited and thus more will contract. Physiologically, a skeletal muscle membrane is getting depolarized by a stimulus. The depolarization stimulus will allow for Na+ to flow into the cell which allows the action potential to flow down into the T-tubule. The DHP receptor will open, which is connected to the RyR Ca2+ release channel to open. This allows for calcium to flow into the cytoplasm from sarcoplasmic reticulum. The calcium ion binds to troponin which allows tropomyosin to move off the actin-myosin binding sites. The myosin will bind to the actin binding site and cross bridge cycling will take place causing a muscle contraction. Therefore, the more depolarized the cells are (from a higher stimulus intensity), the more calcium will be in the cell to bind to troponin, which

Skeletal muscle which is responsible for locomotor movement is under voluntary control. Skeletal muscles lack an ion channels that are responsible for the depolarization of membrane, such as voltage-gated sodium channels. That means they have no intrinsic activity. That is why the nerve impulse is the source of stimulation for skeletal muscle activity (Philip M., 2006). When an action potential travels to the skeletal muscle along the motor neuron, the neuromuscular junction releases acetylcholine that binds to the sarcolemme receptor. The sarcomere, which is composed of contractile units, is consist of alternating thick (myosin) and thin (actin) filaments. A sliding mechanism happens between the thin and thick filaments, where the myosin pulls

It has been known that contractile ring (CR) is composed of two major proteins F-actin and myosin II. This CR formed under the plasma membrane and the cytokinesis is happened based on the contraction of this CR. Therefore, many studies are attributed the CR contraction to the sliding-filament theory which explain the contraction in muscle sarcomeres (1,2). However, there are many differences in the organization of the actomyosin in CR and sarcomere. For example, F-actin in CR can organized in parallel manner and in disordered network compared to its antiparallel organization in sarcomere (3-5). In addition, the dependency of cytokinesis on myosin II has a wide variances compared to the dependency of sarcomere contraction on myosin II. For example, the current study showed that myosin II is a critical factor for contraction in cytokinesis (6). Ma et al (2012) proved that using of an engineered myosin II which lacks motor activity is enough for the CR contraction (7). In the budding yeast, the cytokinesis is driving mainly by F-actin disassembly (8,9).

All organisms, from humans to simple bacteria, have a necessity to move in order to adapt to changes in their external or internal environment, navigate towards food, and avoid dangers. Even cells are teeming with motion as they reorganize organelles, nucleic acids, and proteins. At the molecular level, two types of elements assist in the control movements of the cell and the organism as a whole: molecular-motor proteins and intricate complexes of protein filaments that make up the cytoskeleton of the cell (Vale and Milligan, 2000). Myosin is a family of motor protein that act as enzymes in the hydrolysis of adenosine triphosphate (ATP) to form adenosine diphosphate (ADP) and inorganic phosphate (Pi), The energy released by this reaction to drive the movement of molecules and contraction of muscle fibers (Grigorenko et al., 2007). A remarkable part of evolution is that the same mechanisms that control of contraction of muscles by myosin, are also used to propel

Beta2-adrenergic agonist work by stimulating beta2-adrenergic receptors and increasing cylic 3’5’ adenosine monophosphate, or cAMP (Arcangelo et al, 2017). The increase of cAMP results in relaxation of the smooth muscle of the airway. The cAMP also accelerates the activity of the bronchial ciliary (Arcangelo et al, 2017). Short-acting (Ventolin HFA) and long-acting (monotherapy not recommended, but a long-acting beta2-adrenergic agonist that’s combined with inhaled corticosteroids is Symbicort).