The Relation of Endothelial Cell Regulation of Contractility of the Heart to the Supply of Oxygen
Malcolm J. Lewis, Ajay M. Shah in Endothelial Modulation of Cardiac Function, 2020
The degree to which changes in the structure of the thick filament, as distinct from those produced in the regulatory proteins of the thin filament, may occur in response to phosphorylations can be examined in natural thick filaments isolated from cardiac muscle (Weisberg and Winegrad, 1996). This method allows one to visualise individual thick filaments by negative staining and transmission electron microscopy. The dimensions of the individual thick filaments can be measured in the micrographs, and the optical diffraction pattern produced by laser illumination of the micrographs contains information about the position and the relative degree of order of the cross bridges with respect to the backbone of the thick filament. Incubation of the thick filaments with PKA and ATP produces phosphorylation of C protein without affecting the regulatory light chain of myosin (LC2) because LC2 is phosphorylated only by a Ca-calmodulin regulated enzyme. The distance of the end of the cross bridge, which contains the actin binding site, from the backbone of the thick filament can be calculated from the difference in the widths of the thick filament where there are cross bridges and the width in the central bare zone that contains no cross bridges. The position of the reflections along the 43 nm layer line in the optical diffraction pattern indicates how far the center of mass of the cross bridge lies from the axis of the thick filament. With the information about the relative positions of two points in the cross bridges, changes in orientation may be detectable.
Energy Demand of Muscle Machines
Peter W. Hochachka in Muscles as Molecular and Metabolic Machines, 2019
Muscle shortens by as much as a third of its original length as it contracts. How can we explain this shortening? Some three decades ago, two laboratories (the first headed by A. Huxley and R. Niedergerke, the second by H. Huxley and J. Hanson) independently proposed a sliding filament model of contraction based on X-ray, light microscopic, and electron microscopic studies. There are three essential features in this model: Thick and thin filament lengths do not change during muscle contraction.Sarcomere length decreases during contraction because the two types of filaments overlap more; i.e., thick and thin filaments are moved past each other in contraction.Force is generated by a process that is coupled to the movement of thick and thin filaments past each other.
Vascular smooth muscle: excitation, contraction and relaxation
Neil Herring, David J. Paterson in Levick's Introduction to Cardiovascular Physiology, 2018
As in the heart, contraction depends on crossbridge formation between thick myosin filaments (2.2 |im x 0.315 gm) and overlapping, parallel thin actin filaments (1.5 gm x 0.037 gm) (Figure 12.3). However, the similarities end here. The smooth muscle thin filament is longer than in cardiac muscle, allowing greater shortening, and it lacks troponin, the cardiac Ca2+- dependent regulatory protein. Troponin is replaced by the proteins caldesmon and calponin on VSM thin filaments. The myosin also differs from that in the heart, and only participates in contraction when phosphorylated, that is, when phosphate groups are added to it, by the enzyme MLCK. Therefore, VSM contraction depends primarily on thick-filament rather than thin-filament activation.
High sensitivity troponins in contemporary cardiology practice: are we turning a corner?
Published in Expert Review of Cardiovascular Therapy, 2018
Mark Mariathas, Bartosz Olechowski, Michael Mahmoudi, Nick Curzen
Myofibrils are the basic contractile apparatus of myocytes. Each myofibril is composed of a thick and a thin filament. The thick filament is made up of myosin whilst actin makes up the thin filament. Troponins are classified as cardiac regulatory proteins that control the calcium-mediated interaction between actin and myosin. There are three subunits of the troponin complex: troponin C, I, and T [5]. Cardiac troponin I (cTnI) is cardiac-specific and, although cardiac troponin T can also be found in skeletal muscle, this subtype is not usually detected in currently available assays [6]. As a consequence, the measurement of cTn is considered to be extremely specific for cardiomyocyte injury [7]. It is this concept that has cemented the use of cTn assays in the modern diagnosis and management of acute coronary syndromes (ACS).
Effect of nebivolol on altered skeletal and cardiac muscles induced by dyslipidemia in rats: impact on oxidative and inflammatory machineries
Published in Archives of Physiology and Biochemistry, 2022
Ghada Farouk Soliman, Omnia Mohamed Abdel-Maksoud, Mohamed Mansour Khalifa, Laila Ahmed Rashed, Walaa Ibrahim, Heba Morsi, Hanan Abdallah, Nermeen Bastawy
Reactive oxygen species (ROS) are important for the regulation of several body functions (Di Meo et al.2016). They are generated in skeletal muscles both during rest and contraction (Powers et al.2011). Mitochondria are major sources of ROS within the striated muscle cell (Görlach et al.2015). The skeletal muscles contain abundant antioxidant Defence system to protect against changes in the redox state. Data exist regarding the deleterious effects of oxidative stress within striated muscle tissues at several levels including cell membrane, sarcoplasmic reticulum, up to myofibrils (Powers et al.2011). Thin filament protein oxidation negatively affects contractile function in striated muscles by reducing calcium sensitivity of the myofilament (Lamb and Westerblad 2011, Steinberg 2013). Changes may occur in titin as a result of oxidative stress in striated muscles (Beckendorf and Linke 2015). Superoxide generated within striated muscle fibres causes oxidation of the ryanodine receptor and, thus, interferes with calcium release (Cherednichenko et al.2004, Xia et al.2003). Glutathione (GSH) is a hydrogen donor formed mainly in the liver, and its reduced form plays important roles in reducing H2O2 and some other cellular antioxidants (Powers et al.2011, Di Meo et al.2016). In addition to diminished expression of cardiac antioxidant enzymes with resultant oxidative stress by the effect of hypercholesterolaemia (Csonka et al.2016).
Early clinical and pre-clinical therapy development in Nemaline myopathy
Published in Expert Opinion on Therapeutic Targets, 2022
Gemma Fisher, Laurane Mackels, Theodora Markati, Anna Sarkozy, Julien Ochala, Heinz Jungbluth, Sithara Ramdas, Laurent Servais
Nemaline rods that are seen on Gömöri trichome staining are the histological hallmark of NM. The rods are located in proximity to Z-lines and are considered to be derived from proteins involved in Z-line assembly and maintenance [16,25]. Both Z-lines and rods have a similar lattice structure and comprise similar proteins, which include α-actinin, actin, tropomyosin, myotilin, γ-filamin, cofilin-2, telethonin and nebulin [16,25]. The precise mechanisms of formation are uncertain, although they have been noted to occur in metabolic conditions (Complex 1 deficiency [26]), certain infections [4], inflammatory conditions [27] and with some drugs (e.g. Zidovudine [28])[29]. Nemaline rods are, however, likely to be an epiphenomenon that does not explain all of the pathological mechanisms of NM [16]. Other relevant mechanisms include altered thin filament calcium sensitivity and impaired thick and thin filament interactions resulting in an excitation-contraction disturbance, as well as more general disturbances in thin filament protein turnover [7,30].
Related Knowledge Centers
- Actin
- Muscle Contraction
- Myofibril
- Myosin
- Protein
- Striated Muscle Tissue
- Titin
- Skeletal Muscle
- Protein Filament
- Muscle Cell