Skeletal Muscle
Charles Paul Lambert in Physiology and Nutrition for Amateur Wrestling, 2020
Skeletal muscle contraction involves many muscle proteins as well as sodium (Na+) and potassium (K+) and adenosine triphosphate (ATP), and vital ions such as magnesium (Mg2+) and calcium (Ca2+). The whole muscle contracts by way of individual sarcomere shortening. A sarcomere is Z-line to Z-line. After the ATP is broken down, the myosin head (thick filament head) cocks, and the release of Ca2+ from the sarcoplasmic reticulum upon electrical stimulation through the T-tubule system ensures that Ca2+ binds to troponin. Once the Ca2+ binds to troponin, tropomyosin moves away from the myosin head binding site on actin. The myosin head binds and muscle contraction ensues—myosin head moving actin. The ATP then binds to the myosin head again, is split and released from actin, Ca2+ is taken back up into the sarcoplasmic reticulum and relaxation ensues, or the process of shortening continues if Ca2+ is still in the local environment.
Muscle Electrophysiology
Lara Wijayasiri, Kate McCombe, Paul Hatton, David Bogod in The Primary FRCA Structured Oral Examination Study Guide 1, 2017
As the action potential travels down the T-tubules, which lie very close to the sarcoplasmic reticulum, it triggers calcium release channels (i.e. the ryanodine receptors) on the sarcoplasmic reticulum to open, resulting in an influx of intracellular Ca2+. This Ca2+ binds onto troponin, bringing about a conformational change in the troponin–tropomyosin complex, which results in the exposure of the myosin binding sites on the actin filaments. The myosin heads bind to actin and perform a ratchet-type movement towards the centre of the sarcomeres, dubbed ‘the power stroke’. ATP then binds onto the myosin head, allowing it to detach from the actin. The hydrolysis of this ATP enables the myosin head to re-orientate itself ready for the next power stroke. The muscle relaxes when intracellular Ca2+ levels decrease. Rigor mortis occurs due to the lack of ATP, which prevents the detachment of the myosin heads from actin and hence the filaments are held in sustained contraction.
The Swinging Lever Arm Mechanism: A Most Prominent Current Dogma
Haruo Sugi in Mysteries in Muscle Contraction, 2017
Although the contraction model of Huxley–Simmons (1971) that force generation in the muscle results from the tilting of myosin heads (Fig. 8) was not supported experimentally, it is still believed that the unitary myofilament sliding is caused by some conformational changes of myosin heads attached to actin filaments, as predicted by H. E. Huxley (Fig. 4), a great pioneer who opened the current research field in muscle contraction. I will first explain the structure of the myosin head, which was determined crystallographically, since the current dogma of muscle contraction has been constructed on it.
Myosin light chain kinase regulates intestinal permeability of mucosal homeostasis in Crohn’s disease
Published in Expert Review of Clinical Immunology, 2020
Many studies have demonstrated how MLCK directly regulates the ability of the cytoskeleton to activate the TJ barrier [48,53,54]. Ca2+/calmodulin-dependent MLCK phosphorylates the myosin RLC and activates myosin in the smooth muscle. Then, ATPase in the myosin head is activated to hydrolyze ATP, thereby converting the chemical energy to mechanical forces and motion [55]. At the same time, actin assembles to form actin filaments. Then, the heavy chain motor domain of myosin reversibly binds to actin filaments, leading to cyclic interaction between actin and myosin. With hydrolyzation of ATP (the basis of energy) and assembly of actin (the basis of structure), interaction between MLCK and skeletal proteins contributes to the interplay and contraction of skeletal proteins, finally leading to contraction of the intestinal cells [39]. With contraction of the cytoskeleton, the paracellular pathways sealed by the TJ are activated to increase intestinal permeability. Additionally, Rho-associated kinase (ROCK) has a similar role in myosin phosphorylation and activation [56].
Current and emerging pharmacotherapy for the management of hypertrophic cardiomyopathy
Published in Expert Opinion on Pharmacotherapy, 2023
Akiva Rosenzveig, Neil Garg, Shiavax J. Rao, Amreen K. Kanwal, Arjun Kanwal, Wilbert S. Aronow, Matthew W. Martinez
The essential unit of contraction in cardiac myocytes is the sarcomere [20]. Myosin is the molecular motor of the sarcomere that hydrolyzes adenosine triphosphate (ATP) to interact with the thin filament actin. However, for every given contraction, only 10% of myosin molecules are utilized to generate force [21], thus preventing unnecessary energy utilization. During relaxation, paired myosin head domains can interact in either a super relaxed state (SRX), where neither head can interact with actin filaments, or in a disordered state (DRX), where one myosin head is free to hydrolyze ATP and interacts with actin [22]. The predominant myosin isoform, MYH7 (B-myosin heavy chain), and myosin-binding protein C (MYBPC) harbor most of the pathogenic variants in HCM [23]. These pathologic variants increase the proportion of myosin heads in DRX leading to hypercontractility and increased energy expenditure [22]. In these individuals, hypercontractility and impaired diastolic function precede left ventricular hypertrophy [24,25].
Prenatal Diagnosis of Isolated Right Ventricular Non-Compaction Cardiomyopathy with an MYH7 Likely Pathogenic Variant
Published in Fetal and Pediatric Pathology, 2023
Weiming Yu, Mary Ann Thomas, Lindsay Mills, James R. Wright
Genetic analysis by whole exome sequence analysis in this case identified a heterozygous MYH7 missense likely pathogenic variant with nucleotide sequence change replacing arginine with histidine at codon 712 (designated Arg712His) in the head region between codons 181 and 937 that contains the majority of the myosin head domains. The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant has been identified in two individuals affected with LVNC, and has also been associated with hypertrophic cardiomyopathy [19]. Therefore, this variant has been classified as likely pathogenic.
Related Knowledge Centers
- Actin
- Coiled Coil
- Muscle Contraction
- Myofilament
- Myosin
- Polymer
- Protein Isoform
- Protein Filament
- Atp Hydrolysis
- Regulation of Gene Expression