scholarly journals Structural basis of the super- and hyper-relaxed states of myosin II

2021 ◽  
Vol 154 (1) ◽  
Author(s):  
Roger Craig ◽  
Raúl Padrón

Super-relaxation is a state of muscle thick filaments in which ATP turnover by myosin is much slower than that of myosin II in solution. This inhibited state, in equilibrium with a faster (relaxed) state, is ubiquitous and thought to be fundamental to muscle function, acting as a mechanism for switching off energy-consuming myosin motors when they are not being used. The structural basis of super-relaxation is usually taken to be a motif formed by myosin in which the two heads interact with each other and with the proximal tail forming an interacting-heads motif, which switches the heads off. However, recent studies show that even isolated myosin heads can exhibit this slow rate. Here, we review the role of head interactions in creating the super-relaxed state and show how increased numbers of interactions in thick filaments underlie the high levels of super-relaxation found in intact muscle. We suggest how a third, even more inhibited, state of myosin (a hyper-relaxed state) seen in certain species results from additional interactions involving the heads. We speculate on the relationship between animal lifestyle and level of super-relaxation in different species and on the mechanism of formation of the super-relaxed state. We also review how super-relaxed thick filaments are activated and how the super-relaxed state is modulated in healthy and diseased muscles.

2021 ◽  
Vol 153 (3) ◽  
Author(s):  
Marco Caremani ◽  
Luca Fusi ◽  
Marco Linari ◽  
Massimo Reconditi ◽  
Gabriella Piazzesi ◽  
...  

Contraction of skeletal muscle is regulated by structural changes in both actin-containing thin filaments and myosin-containing thick filaments, but myosin-based regulation is unlikely to be preserved after thick filament isolation, and its structural basis remains poorly characterized. Here, we describe the periodic features of the thick filament structure in situ by high-resolution small-angle x-ray diffraction and interference. We used both relaxed demembranated fibers and resting intact muscle preparations to assess whether thick filament regulation is preserved in demembranated fibers, which have been widely used for previous studies. We show that the thick filaments in both preparations exhibit two closely spaced axial periodicities, 43.1 nm and 45.5 nm, at near-physiological temperature. The shorter periodicity matches that of the myosin helix, and x-ray interference between the two arrays of myosin in the bipolar filament shows that all zones of the filament follow this periodicity. The 45.5-nm repeat has no helical component and originates from myosin layers closer to the filament midpoint associated with the titin super-repeat in that region. Cooling relaxed or resting muscle, which partially mimics the effects of calcium activation on thick filament structure, disrupts the helical order of the myosin motors, and they move out from the filament backbone. Compression of the filament lattice of demembranated fibers by 5% Dextran, which restores interfilament spacing to that in intact muscle, stabilizes the higher-temperature structure. The axial periodicity of the filament backbone increases on cooling, but in lattice-compressed fibers the periodicity of the myosin heads does not follow the extension of the backbone. Thick filament structure in lattice-compressed demembranated fibers at near-physiological temperature is similar to that in intact resting muscle, suggesting that the native structure of the thick filament is largely preserved after demembranation in these conditions, although not in the conditions used for most previous studies with this preparation.


2018 ◽  
Author(s):  
Pertici ◽  
M. Caremani ◽  
M. Reconditi

ABSTRACTThe evidence, in both resting and active muscle, for the presence of an I-band spring element like titin that anchors the Z line to the end of the thick filament did not yet produce a proper theoretical treatment in a complete model of the half-sarcomere. The textbook model developed by A.F. Huxley and his collaborators in 1981, which provides that the half-sarcomere compliance is due to the contribution of the compliances of the thin and thick filaments and actin-attached myosin motors, predicts that at any sarcomere length the absence of attached motors results in an infinite half-sarcomere compliance, in contrast with the observations. Growing evidence for the presence of a titin-like I-band spring urges the 1981 model to be implemented to include the contribution of this element in the mechanical model of the half-sarcomere. The model described here represents a tool for the interpretation of measurements of half-sarcomere compliance at long sarcomere lengths and for investigations of the possible role of titin as the mechano-sensor in thick filament regulation.


2020 ◽  
Vol 43 ◽  
Author(s):  
Thomas Parr

Abstract This commentary focuses upon the relationship between two themes in the target article: the ways in which a Markov blanket may be defined and the role of precision and salience in mediating the interactions between what is internal and external to a system. These each rest upon the different perspectives we might take while “choosing” a Markov blanket.


Crisis ◽  
2016 ◽  
Vol 37 (3) ◽  
pp. 212-217 ◽  
Author(s):  
Thomas E. Joiner ◽  
Melanie A. Hom ◽  
Megan L. Rogers ◽  
Carol Chu ◽  
Ian H. Stanley ◽  
...  

Abstract. Background: Lowered eye blink rate may be a clinically useful indicator of acute, imminent, and severe suicide risk. Diminished eye blink rates are often seen among individuals engaged in heightened concentration on a specific task that requires careful planning and attention. Indeed, overcoming one’s biological instinct for survival through suicide necessitates premeditation and concentration; thus, a diminished eye blink rate may signal imminent suicidality. Aims: This article aims to spur research and clinical inquiry into the role of eye blinks as an indicator of acute suicide risk. Method: Literature relevant to the potential connection between eye blink rate and suicidality was reviewed and synthesized. Results: Anecdotal, cognitive, neurological, and conceptual support for the relationship between decreased blink rate and suicide risk is outlined. Conclusion: Given that eye blinks are a highly observable behavior, the potential clinical utility of using eye blink rate as a marker of suicide risk is immense. Research is warranted to explore the association between eye blink rate and acute suicide risk.


2015 ◽  
Vol 36 (3) ◽  
pp. 170-176 ◽  
Author(s):  
Erin N. Stevens ◽  
Joseph R. Bardeen ◽  
Kyle W. Murdock

Parenting behaviors – specifically behaviors characterized by high control, intrusiveness, rejection, and overprotection – and effortful control have each been implicated in the development of anxiety pathology. However, little research has examined the protective role of effortful control in the relation between parenting and anxiety symptoms, specifically among adults. Thus, we sought to explore the unique and interactive effects of parenting and effortful control on anxiety among adults (N = 162). Results suggest that effortful control uniquely contributes to anxiety symptoms above and beyond that of any parenting behavior. Furthermore, effortful control acted as a moderator of the relationship between parental overprotection and anxiety, such that overprotection is associated with anxiety only in individuals with lower levels of effortful control. Implications for potential prevention and intervention efforts which specifically target effortful control are discussed. These findings underscore the importance of considering individual differences in self-regulatory abilities when examining associations between putative early-life risk factors, such as parenting, and anxiety symptoms.


2016 ◽  
Vol 37 (1) ◽  
pp. 31-39 ◽  
Author(s):  
Nicole L. Hofman ◽  
Austin M. Hahn ◽  
Christine K. Tirabassi ◽  
Raluca M. Gaher

Abstract. Exposure to traumatic events and the associated risk of developing Posttraumatic stress disorder (PTSD) symptoms is a significant and overlooked concern in the college population. It is important for current research to identify potential protective factors associated with the development and maintenance of PTSD symptoms unique to this population. Emotional intelligence and perceived social support are two identified protective factors that influence the association between exposure to traumatic events and PTSD symptomology. The current study examined the mediating role of social support in the relationship between emotional intelligence and PTSD symptoms. Participants included 443 trauma-exposed university students who completed online questionnaires. The results of this study indicated that social support mediates the relationship between emotional intelligence and reported PTSD symptoms. Thus, emotional intelligence is significantly associated with PTSD symptoms and social support may play an integral role in the relationship between emotional intelligence and PTSD. The current study is the first to investigate the role of social support in the relationship between emotional intelligence and PTSD symptoms. These findings have important treatment and prevention implications with regard to PTSD.


2017 ◽  
Vol 16 (3) ◽  
pp. 155-159 ◽  
Author(s):  
Peizhen Sun ◽  
Jennifer J. Chen ◽  
Hongyan Jiang

Abstract. This study investigated the mediating role of coping humor in the relationship between emotional intelligence (EI) and job satisfaction. Participants were 398 primary school teachers in China, who completed the Wong Law Emotional Intelligence Scale, Coping Humor Scale, and Overall Job Satisfaction Scale. Results showed that coping humor was a significant mediator between EI and job satisfaction. A further examination revealed, however, that coping humor only mediated two sub-dimensions of EI (use of emotion and regulation of emotion) and job satisfaction. Implications for future research and limitations of the study are discussed.


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