{"title":"Adaptations for extremely high muscular power output: why do muscles that operate at intermediate cycle frequencies generate the highest powers?","authors":"Graham N Askew","doi":"10.1007/s10974-022-09640-2","DOIUrl":"10.1007/s10974-022-09640-2","url":null,"abstract":"<p><p>The pectoralis muscles of the blue-breasted quail Coturnix chinensis generate the highest power output over a contraction cycle measured to date, approximately 400 W kg<sup>- 1</sup>. The power generated during a cyclical contraction is the product of work and cycle frequency (or standard operating frequency), suggesting that high powers should be favoured by operating at high cycle frequencies. Yet the quail muscles operate at an intermediate cycle frequency (23 Hz), which is much lower than the highest frequency skeletal muscles are capable of operating (~ 200 Hz in vertebrates). To understand this apparent anomaly, in this paper I consider the adaptations that favour high mechanical power as well as the trade-offs that occur between force and muscle operating frequency that limit power. It will be shown that adaptations that favour rapid cyclical contractions compromise force generation; consequently, maximum power increases with cycle frequency to approximately 15-25 Hz, but decreases at higher cycle frequencies. At high cycle frequencies, muscle stress is reduced by a decrease in the crossbridge duty cycle and an increase in the proportion of the muscle occupied by non-contractile elements such as sarcoplasmic reticulum and mitochondria. Muscles adapted to generate high powers, such as the pectoralis muscle of blue-breasted quail, exhibit: (i) intermediate contraction kinetics; (ii) a high relative myofibrillar volume; and (iii) a high maximum shortening velocity and a relatively flat force-velocity relationship. They are also characterised by (iv) operating at an intermediate cycle frequency; (v) utilisation of asymmetrical length trajectories, with a high proportion of the cycle spent shortening; and, finally, (vi) relatively large muscles. In part, the high power output of the blue-breasted quail pectoralis muscle can be attributed to its body size and the intermediate wing beat frequency required to generate aerodynamic force to support body mass, but in addition specialisations in the contractile and morphological properties of the muscle favour the generation of high stress at high strain rates.</p>","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":"44 2","pages":"107-114"},"PeriodicalIF":1.8,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10329623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10191804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daryl M Okamura, Elizabeth D Nguyen, Sarah J Collins, Kevin Yoon, Joshua B Gere, Mary C M Weiser-Evans, David R Beier, Mark W Majesky
{"title":"Mammalian organ regeneration in spiny mice.","authors":"Daryl M Okamura, Elizabeth D Nguyen, Sarah J Collins, Kevin Yoon, Joshua B Gere, Mary C M Weiser-Evans, David R Beier, Mark W Majesky","doi":"10.1007/s10974-022-09631-3","DOIUrl":"10.1007/s10974-022-09631-3","url":null,"abstract":"<p><p>Fibrosis-driven solid organ failure is a major world-wide health burden with few therapeutic options. Spiny mice (genus: Acomys) are terrestrial mammals that regenerate severe skin wounds without fibrotic scars to evade predators. Recent studies have shown that spiny mice also regenerate acute ischemic and traumatic injuries to kidney, heart, spinal cord, and skeletal muscle. A common feature of this evolved wound healing response is a lack of formation of fibrotic scar tissue that degrades organ function, inhibits regeneration, and leads to organ failure. Complex tissue regeneration is an extremely rare property among mammalian species. In this article, we discuss the evidence that Acomys represents an emerging model organism that offers a unique opportunity for the biomedical community to investigate and clinically translate molecular mechanisms of scarless wound healing and regeneration of organ function in a mammalian species.</p>","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":"44 2","pages":"39-52"},"PeriodicalIF":1.8,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12154453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10544116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Participation and performance characteristics in half-marathon run: a brief narrative review.","authors":"Pantelis Theodoros Nikolaidis, Beat Knechtle","doi":"10.1007/s10974-022-09633-1","DOIUrl":"https://doi.org/10.1007/s10974-022-09633-1","url":null,"abstract":"<p><p>Half-marathon (HM) is a running sport of increasing popularity in both sexes and in all age groups worldwide during the last years. Many studies have examined several aspects of HM, such as performance and participation trends, sex and age differences, physiological correlates, and training; however, no comprehensive review has ever been contacted to summarize the recently accumulated knowledge. Therefore, the aim of the present study was to review all previous research in this sport, focusing on participation and performance aspects. It was shown that HM runners had similar anthropometric and physiological characteristics as full-marathon runners which should be attributed to the affinity of these two races in terms of metabolic demands. Performance in HM was related with superior scores in aerobic capacity (maximal oxygen uptake, anaerobic threshold and running economy) and training characteristics (sport experience, weekly distance, training speed, frequency of sessions and long single endurance run distance), and lower scores in adiposity-related scores (e.g. body mass, body mass index, body fat percentage and skinfold thickness). Considering the popularity of HM race and the lack of many original studies (compared to FM race), this is an exciting field for scientific research with a large potential for practical applications, since the majority of HM runners are amateur runners in need of sex-, age- and performance-tailored exercise prescription.</p>","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":"44 2","pages":"115-122"},"PeriodicalIF":2.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10329575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10191783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The cardiovascular challenges in giraffes.","authors":"Christian Aalkjær, Tobias Wang","doi":"10.1007/s10974-022-09626-0","DOIUrl":"https://doi.org/10.1007/s10974-022-09626-0","url":null,"abstract":"<p><p>Giraffes are the highest living animals on Earth and therefore are challenged by gravity more than any other species. In particular the cardiovascular system needs to adapt to this challenge. Giraffes have a mean blood pressure around 200 mmHg, which ensures a mean arterial pressure near the head of 100 mmHg when the giraffe is standing with the neck in a near vertical position. This immediately raises several questions. How do giraffes avoid edema in the legs where the arterial pressure is 300 mmHg or higher? How does the heart produce a pressure of 200 mmHg, and what is the energy required for this endeavor? How can the kidney tolerate a pressure of about 200 mmHg and does this mean that giraffes have a high glomerular filtration rate? What is the arterial pressure in the head of giraffes when they drink, and how is perfusion of the brain maintained when they lift their head after drinking? In this short review, we present some answers to these questions.</p>","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":"44 2","pages":"53-60"},"PeriodicalIF":2.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10194592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jakob Wang, Emil Rindom, Thomas Groennebaek, Peter Sieljacks, Jesper Emil Jakobsgaard, Jean Farup, Kristian Vissing, Thomas Holm Pedersen, Frank Vincenzo de Paoli
{"title":"Six weeks of high-load resistance and low-load blood flow restricted training increase Na/K-ATPase sub-units α2 and β1 equally, but does not alter ClC-1 abundance in untrained human skeletal muscle.","authors":"Jakob Wang, Emil Rindom, Thomas Groennebaek, Peter Sieljacks, Jesper Emil Jakobsgaard, Jean Farup, Kristian Vissing, Thomas Holm Pedersen, Frank Vincenzo de Paoli","doi":"10.1007/s10974-023-09644-6","DOIUrl":"https://doi.org/10.1007/s10974-023-09644-6","url":null,"abstract":"<p><p>Contractile function of skeletal muscle relies on the ability of muscle fibers to trigger and propagate action potentials (APs). These electrical signals are created by transmembrane ion transport through ion channels and membrane transporter systems. In this regard, the Cl<sup>-</sup> ion channel 1 (ClC-1) and the Na<sup>+</sup>/K<sup>-</sup>-ATPase (NKA) are central for maintaining ion homeostasis across the sarcolemma during intense contractile activity. Therefore, this randomized controlled trial aimed to investigate the changes in ClC-1 and specific NKA subunit isoform expression in response to six weeks (18 training sessions) of high-load resistance exercise (HLRE) and low-load blood flow restricted resistance exercise (BFRRE), respectively. HLRE was conducted as 4 sets of 12 repetitions of knee extensions performed at 70% of 1 repetition maximum (RM), while BFRRE was conducted as 4 sets of knee extensions at 30% of 1RM performed to volitional fatigue. Furthermore, the potential associations between protein expression and contractile performance were investigated. We show that muscle ClC-1 abundance was not affected by either exercise modality, whereas NKA subunit isoforms [Formula: see text]<sup>2</sup> and [Formula: see text]<sup>1</sup> increased equally by appx. 80-90% with BFRRE (p < 0.05) and 70-80% with HLRE (p < 0.05). No differential impact between exercise modalities was observed. At baseline, ClC-1 protein expression correlated inversely with dynamic knee extensor strength (r=-0.365, p = 0.04), whereas no correlation was observed between NKA subunit content and contractile performance at baseline. However, training-induced changes in NKA [Formula: see text]<sup>2</sup> subunit (r = 0.603, p < 0.01) and [Formula: see text]<sup>1</sup> subunit (r = 0.453, p < 0.05) correlated with exercise-induced changes in maximal voluntary contraction. These results suggest that the initial adaptation to resistance-based exercise does not involve changes in ClC-1 abundance in untrained skeletal muscle, and that increased content of NKA subunits may facilitate increases in maximal force production.</p>","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":"44 1","pages":"25-36"},"PeriodicalIF":2.7,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9693879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nonsense-mediated mRNA decay promote C2C12 cell proliferation by targeting PIK3R5.","authors":"Zhenzhou Huang, Yishu Peng, Yuhui Wei, Yanjie Tan","doi":"10.1007/s10974-022-09639-9","DOIUrl":"https://doi.org/10.1007/s10974-022-09639-9","url":null,"abstract":"<p><p>Nonsense mediated mRNA decay (NMD) is a highly conserved RNA quality control system, which can specifically clear abnormal mRNA and play an important role in tumorigenesis. Myoblast proliferation plays an important role in the repair of skeletal muscle injury and the development of myosarcoma, and is controlled by a variety of transcription factors and signals. The molecular mechanism by which NMD regulates the proliferation of myoblast cells is not completely clear. In this study, we found that the NMD activity of skeletal muscle is high in 1-week-old mice but decreases gradually with age, corresponding to a weakening capacity for muscle growth and regeneration. Here, we provide evidence that NMD plays an important role in myoblast proliferation and apoptosis. In addition, we found that PIK3R5 is an NMD substrate gene which can inhibit AKT activity and C2C12 cell proliferation. Therefore, NMD can target PIK3R5 to enhance AKT activity, which in turn promotes C2C12 cell proliferation. This study provides new insights into NMD regulatory mechanisms in muscular development and into potential novel therapeutic strategies for muscle atrophy.</p>","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":"44 1","pages":"11-23"},"PeriodicalIF":2.7,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9681332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Preservation of shortening velocity and power output in single muscle fibres from patients with idiopathic inflammatory myopathies.","authors":"Franclo Henning, Tertius Abraham Kohn","doi":"10.1007/s10974-022-09638-w","DOIUrl":"https://doi.org/10.1007/s10974-022-09638-w","url":null,"abstract":"<p><p>Idiopathic inflammatory myopathies (IIMs) are autoimmune disorders of skeletal muscle causing weakness and disability. Utilizing single fibre contractility studies, we have previously shown that contractility is affected in muscle fibres from individuals with IIMs. For the current study, we hypothesized that a compensatory increase in shortening velocity occurs in muscle fibres from individuals with IIMs in an effort to maintain power output. We performed in vitro single fibre contractility studies to assess force-velocity relationships and maximum shortening velocity (V<sub>max</sub>) of muscle fibres from individuals with IIMs (25 type I and 58 type IIA) and healthy controls (66 type I and 27 type IIA) and calculated maximum power output (W<sub>max</sub>) for each fibre. We found significantly higher V<sub>max</sub> (mean ± SEM) of fibres from individuals with IIMs, for both type I (1.40 ± 0.31 fibre lengths/s, n = vs. 0.63 ± 0.13 fibre lengths/s; p = 0.0019) and type IIA fibres (2.00 ± 0.17 fibre lengths/s vs 0.77 ± 0.10 fibre lengths/s; p < 0.0001). Furthermore, W<sub>max</sub> (mean ± SEM) was maintained compared to fibres from healthy controls, again for both type I and type IIA fibres (4.10 ± 1.00 kN/m<sup>2</sup>·fibre lengths/s vs. 2.00 ± 0.16 kN/m<sup>2</sup>·fibre lengths/s; p = ns and 9.00 ± 0.64 kN/m<sup>2</sup>·fibre lengths/s vs. 6.00 ± 0.67 kN/m<sup>2</sup>·fibre lengths/s; p = ns respectively). In addition, type I muscle fibres from individuals with IIMs was able to develop maximum power output at lower relative force. The findings of this study suggest that compensatory responses to maintain power output, including increased maximum shortening velocity and improved efficiency, may occur in muscle of individuals with IIMs. The mechanism underlying this response is unclear, and different hypotheses are discussed.</p>","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":"44 1","pages":"1-10"},"PeriodicalIF":2.7,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9689613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Downhill running induced DNA damage enhances mitochondrial membrane permeability by facilitating ER-mitochondria signaling.","authors":"Junping Li, Binting Zhao, Shengju Chen, Zhen Wang, Kexin Shi, Binkai Lei, Chunxia Cao, Zhifei Ke, Ruiyuan Wang","doi":"10.1007/s10974-022-09634-0","DOIUrl":"https://doi.org/10.1007/s10974-022-09634-0","url":null,"abstract":"<p><p>To observe whether downhill running can lead to DNA damage in skeletal muscle cells and changes in mitochondrial membrane permeability and to explore whether the DNA damage caused by downhill running can lead to changes in mitochondrial membrane permeability by regulating the components of the endoplasmic reticulum mitochondrial coupling structure (MAM). A total of 48 male adult Sprague-Dawley rats were randomly divided into a control group (C, n = 8) and a motor group (E, n = 40). Rats in Group E were further divided into 0 h (E0), 12 h (E12), 24 h (E24), 48 h (E48) and 72 h (E72) after prescribed exercise, with 8 rats in each group. At each time point, flounder muscle was collected under general anaesthesia. The DNA oxidative damage marker 8-hydroxydeoxyguanosine (8-OHdG) was detected by immunofluorescence. The expression levels of the DNA damage-related protein p53 in the nucleus and the EI24 protein and reep1 protein in whole cells were detected by Western blot. The colocalization coefficients of the endoplasmic reticulum protein EI24 and the mitochondrial protein Vdac2 were determined by immunofluorescence double staining, and the concentration of Ca<sup>2+</sup> in skeletal muscle mitochondria was detected by a fluorescent probe. Finally, the opening of the mitochondrial membrane permeability transition pore (mPTP) was detected by immunofluorescence. Twelve hours after downhill running, the mitochondrial membrane permeability of the mPTP opened the most (P < 0.05), the content of 8-OHdG in skeletal muscle peaked (P < 0.05), and the levels of the regulatory protein p53, mitochondrial Ca<sup>2+</sup>, and the EI24 and reep1 proteins peaked (P < 0.01). Moreover, the colocalization coefficients of EI24 and Vdac2 and the Mandes coefficients of the two proteins increased first and then recovered 72 h after exercise (P < 0.05). (1) Downhill running can lead to DNA damage in skeletal muscle cells, overload of mitochondrial Ca<sup>2+</sup> and large opening of membrane permeability transformation pores. (2) The DNA damage caused by downhill running may result in p53 promoting the transcriptional activation of reep1 and EI24, enhancing the interaction between EI24 and Vdac2, and then leading to an increase in Ca<sup>2+</sup> in skeletal muscle mitochondria and the opening of membrane permeability transition pores.</p>","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":"43 4","pages":"185-193"},"PeriodicalIF":2.7,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10451799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Susan M Ronaldson, D George Stephenson, Stewart I Head
{"title":"Calcium and strontium contractile activation properties of single skinned skeletal muscle fibres from elderly women 66-90 years of age.","authors":"Susan M Ronaldson, D George Stephenson, Stewart I Head","doi":"10.1007/s10974-022-09628-y","DOIUrl":"https://doi.org/10.1007/s10974-022-09628-y","url":null,"abstract":"<p><p>The single freshly skinned muscle fibre technique was used to investigate Ca<sup>2+</sup>- and Sr<sup>2+</sup>-activation properties of skeletal muscle fibres from elderly women (66-90 years). Muscle biopsies were obtained from the vastus lateralis muscle. Three populations of muscle fibres were identified according to their specific Sr<sup>2+</sup>-activation properties: slow-twitch (type I), fast-twitch (type II) and hybrid (type I/II) fibres. All three fibre types were sampled from the biopsies of 66 to 72 years old women, but the muscle biopsies of women older than 80 years yielded only slow-twitch (type I) fibres. The proportion of hybrid fibres in the vastus lateralis muscle of women of circa 70 years of age (24%) was several-fold greater than in the same muscle of adults (< 10%), suggesting that muscle remodelling occurs around this age. There were no differences between the Ca<sup>2+</sup>- and Sr<sup>2+</sup>-activation properties of slow-twitch fibres from the two groups of elderly women, but there were differences compared with muscle fibres from young adults with respect to sensitivity to Ca<sup>2+</sup>, steepness of the activation curves, and characteristics of the fibre-type dependent phenomenon of spontaneous oscillatory contractions (SPOC) (or force oscillations) occurring at submaximal levels of activation. The maximal Ca<sup>2+</sup> activated specific force from all the fibres collected from the seven old women use in the present study was significantly lower by 20% than in the same muscle of adults. Taken together these results show there are qualitative and quantitative changes in the activation properties of the contractile apparatus of muscle fibres from the vastus lateralis muscle of women with advancing age, and that these changes need to be considered when explaining observed changes in women's mobility with aging.</p>","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":"43 4","pages":"173-183"},"PeriodicalIF":2.7,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9708809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10442160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jing Xi, Yuanchao Ye, Mohamad Mokadem, Jinxiang Yuan, Masataka Kawai
{"title":"The effect of gender and obesity in modulating cross-bridge function in cardiac muscle fibers.","authors":"Jing Xi, Yuanchao Ye, Mohamad Mokadem, Jinxiang Yuan, Masataka Kawai","doi":"10.1007/s10974-022-09627-z","DOIUrl":"https://doi.org/10.1007/s10974-022-09627-z","url":null,"abstract":"<p><p>The effect of obesity on cross-bridge (CB) function was investigated in mice lacking functional Melanocortin-4 Receptor (MC4R<sup>-/-</sup>), the loss of which causes dilated cardiomyopathy (DCM) in humans and mice. Skinned cardiac muscle fibers from male and female mice were used, and activated in the presence of Ca<sup>2+</sup>. To characterize CB kinetics, we changed the length of fibers in sinewaves (15 frequencies: 1‒187 Hz) at a small amplitude (0.2%L<sub>0</sub>), studied concomitant tension transients, and deduced the kinetic constants of the CB cycle from the ATP and Pi effects. In males, active tension and stiffness during full activation and rigor were ~ 1.5X in WT compared to MC4R<sup>-/-</sup> mice. This effect was not observed in females. We also observed that ATP binding and subsequent CB detachment steps were not altered by the mutation/gender. The equilibrium constant of the force generation step (K<sub>4</sub>) and Pi release step (association constant: K<sub>5</sub>) were not affected by the mutation, but there was a gender difference in WT mice: K<sub>4</sub> and K<sub>5</sub> were ~ 2.2X in males than in females. Concomitantly, the forward rate constant (r<sub>4</sub>) and backward rate constant (r<sub>-4</sub>) of the force generation step were 1.5-2.5X in muscles from female MC4R<sup>-/-</sup> mice relative to male MC4R<sup>-/-</sup> mice. However, these effects did not cause a significant difference in CB distributions among six CB states. In both genders, Ca<sup>2+</sup> sensitivity decreased slightly (0.12 pCa unit) in mutants. We conclude that the CB functions are differentially affected both by obesity induced in the absence of functional MC4R<sup>-/-</sup> and gender.</p>","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":"43 4","pages":"157-172"},"PeriodicalIF":2.7,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10451498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}