The Japanese journal of physiology最新文献

{"title":"The Ca2+ sensitizer CK‐2066260 increases myofibrillar Ca2+ sensitivity and submaximal force selectively in fast skeletal muscle","authors":"D. Hwee, A. Cheng, J. Hartman, A. Hinken, Kenneth H. Lee, Nickie Durham, A. Russell, F. Malik, H. Westerblad, J. Jasper","doi":"10.1113/JP273248","DOIUrl":"https://doi.org/10.1113/JP273248","url":null,"abstract":"We report that the small molecule CK‐2066260 selectively slows the off‐rate of Ca2+ from fast skeletal muscle troponin, leading to increased myofibrillar Ca2+ sensitivity in fast skeletal muscle. Rodents dosed with CK‐2066260 show increased hindlimb muscle force and power in response to submaximal rates of nerve stimulation in situ. CK‐2066260 has no effect on free cytosolic [Ca2+] during contractions of isolated muscle fibres. We conclude that fast skeletal muscle troponin sensitizers constitute a potential therapy to address an unmet need of improving muscle function in conditions of weakness and premature muscle fatigue.","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77004457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thank you to our expert Referees","authors":"Christian, Aaucci, Angela, Abbott, Stephen, Ackland, Gareth, Adachi-Akahane, Satomi, Adams, Gregory, Affourtit, Charles, Aguilar, Martin, Ahern, Gérard, Ahmed, Zaghloul, Ainslie, Philip, Ajijola, Olujimi, Akar, Fadi, Akk, Gustav, Alberici, Luciane, Alexander, Barbara, Lacy, R. Todd, Allen, Paul, Allison, Beth, Alonso, José Manuel, Alonso-Vale, María Isabel, Alper, Seth, Altier, Christophe, Alway, Markus, Amarillo, Yimy, Amberg, Ambudkar, Appleyard, Lars, Armitage, James, Armstead, William, Armstrong, Arreola, Jonathan, Artigas, Pablo, Ashmore, Aslam, Muhammad, Atherton, Attwell, David, Auerbach, Anthony, Averina, Viktória, Avila, Guillermo, Avolio, Alberto, Awatramani, Keith, Baccei, Mark, Backx, Ole, Bagher, Kathrin, Bangsbo, Jens, Banke, Tue, Bannister, Matthias, Bassingthwaighte, Jason, Batten, Alan, Bauer, Bautista, Diana, Bayliss, Bruce, Beard, Beaudin, Andrew, Beaumont, Eric, Beckel, Gregor, Benedetti, Laurence, Boecker, Henning, Boedtkjer, Ebbe, Boesmans","doi":"10.1113/JP274039","DOIUrl":"https://doi.org/10.1113/JP274039","url":null,"abstract":"Aalkjaer, Christian Aaucci, Angela Abbott, Stephen Ackland, Gareth Adachi-Akahane, Satomi Adams, Gregory Affourtit, Charles Aguilar, Martin Ahern, Gerard Ahmed, Zaghloul Ainslie, Philip Ajijola, Olujimi Akar, Fadi Akk, Gustav Alberici, Luciane Alexander, Barbara Alexander, Lacy Alexander, R. Todd Allen, Charles Allen, David Allen, Paul Allison, Beth Alonso, Jose Manuel Alonso-Vale, Maria Isabel Alper, Seth Altier, Christophe Alway, Stephen Amann, Markus Amarillo, Yimy Amberg, Gregory Ambudkar, Indu Amthor, Helge Andersson, Daniel Andersson, Karl-Erik Andresen, Michael Annunziato, Lucio Antunes, Vagner Apell, Hans-Juergen Apodaca, Gerard Appleyard, Suzanne Arabzadeh, Ehsan Araque, Alfonso Arendt-Nielsen, Lars Armitage, James Armstead, William Armstrong, William Arreola, Jorge Art, Jonathan Artigas, Pablo Ashmore, Jonathan Aslam, Muhammad Atherton, Philip Attwell, David Auerbach, Anthony Averina, Viktoria Avila, Guillermo Avolio, Alberto Awatramani, Gautam Baar, Keith Baccei, Mark Backx, Peter Bækgaard Nielsen, Ole Bagher, Pooneh Baker, Stuart Baker-Herman, Tracy Bakker, Erik Balemba, Onesmo Balestra, Costantino Ballanyi, Klaus Ballard, H. Balog, Edward Banach, Kathrin Bangsbo, Jens Banke, Tue Bannister, Roger Bargas, Jose Barkmeier-Kraemer, Julie Barman, Susan Barnes, Jill Barnes, Matthew Barnes, Steven Barrett-Jolley, Richard Barstow, Tom Barth, Daniel Barton, Elisabeth Barton, Matthias Bassingthwaighte, James Bastian, Amy Bates, David Bates, Jason Batten, T Batterham, Alan Bauer, Anthony Bautista, Diana Bayliss, Douglas Bean, Bruce Beard, Daniel Beart, Philip Beaudin, Andrew Beaumont, Eric Beckel, Jonathan Beckett, Elizabeth Begley, David Behm, David Behnke, Brad Behrendt, Marc Beierlein, Michael Béı̈que, Jean-Claude Belušič, Gregor Benedetti, Fabrizio Bennet, Laura Beraneck, Mathieu Berridge, Michael Bertagnolli, Mariane Bertrand, Daniel Bett, Glenna Bevensee, Mark Beyak, Michael Beyder, Arthur Beyer, Andreas Bezprozvanny, Ilya Bickel, Perry Bie, Peter Bikson, Marom Billups, Brian Binshtok, Alexander Bischofberger, Josef Blaauw, Bert Black, Christopher Blackshaw, Laurence Blain, Grégory Blazev, Ronnie Blevins, James Blikslager, Anthony Blockley, Nicholas Bloodgood, Brenda Bloomfield, Stewart Blouin, Jean-Sébastien Bodine, Sue Bodineau, Laurence Boecker, Henning Boedtkjer, Ebbe Boesmans, Werend Boets, Eef Bogdanova, Anna Boix, Fernando Boje, Trine Bollinger, Lance Bonin, Robert Boonstra, Tjeerd Booth, Frank Borges, Ricardo Boric, Mauricio Bornstein, Joel Boron, Walter Borst, Gerard Bosman, Laurens Bosutti, Alessandra Bottinelli, Roberto Botting, Kimberley Bourinet, Emmanuel Bourque, Charles Bourque, Stephane Boushel, Robert Bowen, T. Scott Bowyer, Susan Boychuk, Jeffery Boyett, Mark Bradding, Peter Brainard, George Brégeon, Jérémy Brewer, Allison Brichta, Alan Brierley, Stuart Brittain, John-Stuart Brooks, Susan","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81016639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An intricate balance of muscle damage and protein synthesis: the key players in skeletal muscle hypertrophy following resistance training","authors":"G. Keefe, C. Wright","doi":"10.1113/JP273235","DOIUrl":"https://doi.org/10.1113/JP273235","url":null,"abstract":"The benefits of resistance training for skeletal muscle mass and strength are well characterised. Early adaptations to unaccustomed resistance exercise include increased muscle strength, whereas later adaptations include muscle hypertrophy and further improvements in muscle strength (Schoenfeld, 2010). Although these strength and hypertrophy gains following resistance training are well documented in healthy and clinical populations, the mechanisms surrounding these phenomena are less implicit. The skeletal muscle microenvironment is tightly regulated and responds rapidly to resistance exercise. A single bout of unaccustomed resistance exercise can cause damage to skeletal muscle, where the structural integrity of the myofibres is compromised. This was theorised to be a significant event which stimulates hypertrophic responses within the muscle microenvironment (Schoenfeld, 2010). However, progression through a resistance training programme is marked by an attenuation in muscle damage which is termed the ‘repeated bout effect’. These findings have lead researchers to question the role of muscle damage in muscle hypertrophy following resistance training. One key factor which has an important yet poorly understood association with muscle damage and hypertrophy following resistance exercise is muscle protein synthesis. Previous work by Damas and colleagues has demonstrated that resistance exercise is a potent stimulator of skeletal muscle protein synthesis (Damas et al. 2015). In the hours following an unaccustomed bout of resistance exercise, an increase in myofibrillar muscle protein synthesis (MyoPS) can be detected. Repeated bouts of resistance exercise cause cumulative periods of increased MyoPS where net protein synthesis is greater than protein degradation, thus favouring muscle hypertrophy (Damas et al. 2015). However, the MyoPS response to resistance exercise is not equivocal as the resistance training programme progresses. Attenuation of the MyoPS response to resistance exercise can be observed as early as 3 weeks into a training programme (Brook et al. 2015). Interestingly, the MyoPS response to initial resistance exercise bouts is not correlated with muscle hypertrophy that occurs later in the training programme (Damas et al. 2015). However, the MyoPS response to later bouts of the resistance training programme correlates strongly with muscle hypertrophy (Brook et al. 2015). The authors noted that initial bouts of unaccustomed resistance exercise cause pronounced muscle damage, which stimulates growth mechanisms and increases protein synthesis to support tissue repair. Damas therefore proposed that the lack of correlation between the MyoPS response to initial exercise bouts and subsequent muscle hypertrophy could be due to exercise-induced muscle damage, and that the early MyoPS response is focused on repairing damaged muscle. However, following resistance training the MyoPS response is a more dedicated driver of muscle hypertrophy. Conti","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73190403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adrenaline and the carotid body during hypoglycaemia: an amplifying mechanism?","authors":"P. Katayama","doi":"10.1113/JP273238","DOIUrl":"https://doi.org/10.1113/JP273238","url":null,"abstract":"The moment-to-moment regulation of metabolism is essential to life. It optimises conditions to keep cells working efficiently even when faced with a variety of metabolic challenges that occur constantly in both physiological and pathological situations. To respond adequately to these challenges, a well-orchestrated adjustment at the molecular, cellular, tissue and system levels is necessary. Quite recently the carotid body has been considered as a multifunctional structure. Besides its well-established role in promoting autonomic and ventilatory adjustments to changes in O2, CO2 and/or pH in arterial blood, there is a growing body of scientific evidence revealing that the carotid body can respond to other stimuli such as glucose, hormones, K+, osmolarity, proinflammatory cytokines and temperature (Kumar & Prabhakar, 2012). Because of this unique ability to accurately monitor the chemical composition of arterial blood, the carotid body may be involved in numerous physiological and pathological processes such as hypertension and heart failure. Currently, considerable attention has been paid to elucidate the role of the carotid body in the regulation of metabolism. More specifically, some studies have shown that the carotid body is essential in maintaining body homeostasis during metabolic challenges such as hypoglycaemia. In a recent study published in The Journal of Physiology, Thompson et al. (2016) highlighted that the carotid body plays an important role in a counter-regulatory response to hypoglycaemia. The authors showed that carotid body activation is crucial to match ventilation to the hypermetabolic state induced by hypoglycaemia, avoiding an increase in PaCO2 and consequently acidosis. Using an impressive range of in vivo functional studies, the new discovery was that the carotid body-mediated ventilatory adjustments to hypoglycaemia were adrenaline dependent and mediated by β-adrenoceptors. In anaesthetised Wistar rats, they showed that insulin-induced hypoglycaemia increased ventilation and CO2 sensitivity. Both effects were abolished by either adrenalectomy or propranolol administration, strongly suggesting that these adjustments during hypoglycaemia depend on adrenaline and its β-adrenoceptors. The other arm of the study was to verify the effect of adrenaline itself on ventilation and CO2 sensitivity. Through intravenous adrenaline infusion, Thompson et al. (2016) found that adrenaline mirrored the effects caused by hypoglycaemia, increasing both ventilation and CO2 sensitivity. However, when adrenaline was infused after bilateral carotid sinus nerve section, the rise in minute ventilation was significantly attenuated and PaCO2 was found to be higher compared with control, denoting a clear ventilation–metabolism mismatch. This protocol revealed that the carotid body mediates the ventilatory changes during adrenaline infusion. It is important to note that, to exclude a possible effect of blood pressure changes on ventilation, the autho","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82021400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tracking diaphragm movement by using ultrasound to assess its strength","authors":"A. Connolly, B. Mittendorfer","doi":"10.1113/JP273313","DOIUrl":"https://doi.org/10.1113/JP273313","url":null,"abstract":"Progressive neuromuscular diseases, such as Duchenne muscular dystrophy, but also the normal ageing process, result in muscle atrophy and remodelling (including infiltration with non-contractile fat and connective tissue). These effects impair the ability of muscle to generate and maintain force and endurance. Symptoms including weakness and fatigue are first noticed in ambulatory muscles but do not spare other skeletal muscles, including the respiratory muscles (diaphragm and intercostal muscles) (Sharma & Goodwin, 2006). Respiratory and bulbar muscle weakness interferes with airway clearance, increases risk of recurrent chest infections, and ultimately leads to respiratory failure. In fact, the prognosis for people with progressive neuromuscular disorders depends primarily on the degree of respiratory muscle involvement. In people, respiratory muscle function is typically assessed indirectly by using pulmonary function indices, such as forced vital capacity, peak expiratory and inspiratory pressures, the fluoroscopic sniff test, or nerve conduction studies and electromyography (Sarwal et al. 2013). Nerve conduction studies and electromyography are challenging and uncomfortable. Pulmonary function tests may be difficult to perform and therefore less reliable in people with significant respiratory muscle weakness. In preclinical rodent models, such as the mdx mouse (a model for human Duchenne muscular dystrophy), the standard method to evaluate respiratory muscle strength is ex vivo measured isometric force developed by a small (a few millimeters in width) diaphragm strip. The limitations of this approach include: (i) the single time point of measurement (mice need to be killed to harvest the diaphragm strips), (ii) the strip may not be representative of the whole diaphragm because fibrosis, a major cause of muscle weakness, is not distributed evenly across that diaphragm, and (iii) muscle force development depends on both intrinsic and extrinsic (e.g. innervation) factors, which are not all accounted for ex vivo. In this issue of The Journal of Physiology, Whitehead et al. (2016) describe a newly developed high-frequency, high resolution ultrasonography method to evaluate diaphragm function in vivo in mice. They first validated diaphragm ultrasonography as a reliable measure of in vivo diaphragm function by measuring diaphragm movement amplitude in 8and 18-month-old wild type (WT) and mdx mice and comparing these measurements with ex vivo specific force measurements. They found that ultrasound imaging reliably detected diaphragm dysfunction in mdx mice both at 8 and 18 months of age and the ultrasound-measured diaphragm amplitude measurements correlated strongly with ex vivo-measured isometric force. They then used the ultrasound method to track (serial measure-","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89471576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Passive heat therapy: the next hot thing for cardiovascular health!","authors":"Daniel Lazzam, B-R. Wang, Eric Jong, Pratiek N. Matkar","doi":"10.1113/JP273213","DOIUrl":"https://doi.org/10.1113/JP273213","url":null,"abstract":"Cardiovascular disease is currently the leading cause of death in developed countries across the globe, with myriad risk factors that modern life has only exacerbated. As such, treatments and lifestyle changes that alleviate the risk of cardiovascular disease are of great relevance. While factors like exercise and good diet are known to have such ameliorative effects, patients at high risk of developing cardiovascular diseases are often elderly or obese, and thus may have difficulty exercising on a regular basis. Furthermore, individuals with lower incomes often cannot afford to eat healthily, or such a diet is logistically impossible for them. These factors will only be exacerbated by rapidly rising food prices and increasing populations aggravating socioeconomic phenomena such as food deserts, residential areas devoid of groceries or healthy food options (Rehm et al. 2015). Thus, medically subsidized alternatives to these options are extremely important to explore for those whom a good diet or frequent exercise may be difficult or infeasible. In recent years, several studies have examined thermal therapy as one such alternative, primarily through methods such as saunas and bathing (Imamura et al. 2001; Hu et al. 2012). While the efficacy of thermal therapy on cardiovascular health has at this point been demonstrated by multiple studies, the underlying mechanisms are less understood. However, a recent publication in The Journal of Physiology (Brunt et al. 2016) has helped to elucidate some of these mechanisms. In the paper, Brunt et al. (2016) performed an 8 week study on a cohort of 20 subjects in which the subjects either underwent heat therapy 4–5 times a week for a total of 90 min or were immersed in thermoneutral water as an osmotic and hydrostatic control. The subjects assigned to heat therapy were immersed in 40.5°C water, a temperature sufficient to maintain rectal temperature greater than 38.5°C for 60 min. In contrast, the rectal temperature of the control group remained within 0.2°C of the original temperature. Subjects in both groups were matched for sex, age, height, body mass index and weight, ensuring a representative control group. The authors of the study took a multi-pronged approach in determining the mechanism of action of heat therapy by measuring a variety of processes that they hypothesized could contribute: flow-mediated dilatation, superficial femoral dynamic arterial compliance, aortic pulse wave velocity, carotid intima media thickness, and mean arterial blood pressure. These measurements were taken at the start of the study and every 2 weeks thereafter. The literature has suggested that part of the mechanism by which heat therapy ameliorates cardiovascular health is through alleviation of arterial stiffness (Hu et al. 2012). Consequently, Brunt et al. (2016) hypothesized that flow-mediated dilatation and superficial femoral dynamic compliance would increase with regular heat therapy. Indeed, flow-mediated dilatation s","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77167916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mechanistic basis of the power–time relationship: potential role of the group III/IV muscle afferents","authors":"T. Hureau, R. Broxterman, J. Weavil","doi":"10.1113/JP273333","DOIUrl":"https://doi.org/10.1113/JP273333","url":null,"abstract":"The power–time relationship for highintensity exercise is well known to be hyperbolic and generalizable to multiple exercise modalities in humans and other species. The critical power (CP) is mathematically defined as the asymptote of this hyperbola, while the curvature constant (W′) represents a fixed amount of work that can be performed above CP before reaching exhaustion. Importantly, CP is the highest intensity in which a steady state can be obtained for small muscle mass exercise, as assessed by intramuscular metabolic perturbation, and during wholebody exercise, assessed by oxygen uptake. However, experimental evidence demonstrating that CP represents a threshold for steady state ( CP) or non-steady state (> CP) intramuscular metabolic perturbation during whole-body exercise, a necessity for the validation of the CP concept, has remained elusive. In a recent article published in The Journal of Physiology, Vanhatalo and colleagues aimed to clarify the mechanistic bases of the power–time parameters (i.e. CP and W′) during whole-body exercise in relation to muscle metabolism and fibre type distribution (Vanhatalo et al. 2016). To this end, they performed two experimental protocols with multiple muscle biopsies prior to, and following, high-intensity cycling tests of varying duration. Notably, the authors present the first evidence demonstrating that CP demarcates intensities which result in steady-state ( CP) and non-steady state (> CP) intramuscular metabolic responses for wholebody exercise (i.e. phosphocreatine, creatine, pH, lactate, and glycogen). Moreover, Vanhatalo et al. (2016) documented that a greater CP was associated with a higher type I muscle fibre proportion and a lower type IIx proportion. These findings build upon previous work to further validate the CP concept and extend our understanding of the mechanisms determining the power–time relationship. The authors also determined that the size of the W′ is not proportional to any specific muscle fibre type population, further supporting the growing evidence that W′ is determined by the integration of a multitude of physiological mechanisms. Indeed, by compiling evidence from this study and several other recent publications, questions arise regarding the potential mechanistic role of the group III/IV muscle afferents in determining W′; however, little work has been performed with this focus.","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77890187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skeletal muscle stem cell defects in burn‐induced cachexia","authors":"J. Farup, A. Torcinaro, L. Madaro","doi":"10.1113/JP273095","DOIUrl":"https://doi.org/10.1113/JP273095","url":null,"abstract":"Satellite cells (SCs), the skeletal muscle stem cells, are essential for muscle regeneration in genetic or autoimmune muscle diseases as well as after ischaemic, chemical or mechanical trauma to the myofibres. Furthermore, SCs are the primary source to supply new myonuclei to growing myofibres during non-traumatic mechanical overload. Thus, when SCs are conditionally ablated using a tamoxifen inducible Cre-LoxP system, the addition of myonuclei during overload is abrogated (McCarthy et al. 2011). However, despite the lack of myonuclei addition, substantial hypertrophy could be induced in SC-ablated mice (McCarthy et al. 2011). More recent evidence, however, indicates that the ability of SC-depleted muscles to hypertrophy could be compromised during the later stages of muscle hypertrophy (Fry et al. 2014). Thus, while myonuclei addition, due to the fusion of muscle progenitors, may not be a prerequisite for initial muscle hypertrophy, a functional pool of SCs still play a key role during muscle hypertrophy. In contrast, less is known concerning the role of SCs and myonuclei turnover (e.g. myonuclei loss through apoptosis) during myofibre atrophy. Previous studies indicate that myofibre atrophy, for instance during immobilization or disease (cachexia), is generally not associated with a loss of myonuclei or an increase of DNA damage and apoptosis (Bruusgaard et al. 2012; Suetta et al. 2012). In an intriguing recent paper published in The Journal of Physiology, Fry and colleagues (Fry et al. 2016) explore the potential involvement of SCs and myonuclei apoptosis in young burn patients, a condition characterized by hyper-metabolism and extreme muscle wasting. Biopsies of vastus lateralis muscle were collected from patients (children between 8 and 18 years), with burns encompassing more than 30% of their total body area, during the flow phase of their recovery (characterized by hyper-metabolic demand). Biopsies were also collected from vastus lateralis muscles in a healthy control group, including males between 18 and 29 years of age, for comparison purposes. Through extensive immunohistochemical analyses, the authors collected information on myonuclei apoptosis (deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) and caspase-3 positive myonuclei), SC content and activity Ki67/Myogenic differentiation 1 (MyoD) expression, SC apoptosis (TUNEL positive satellite cells), muscle regeneration by analysing embryonic myosin heavy chain (embMHC) expression and levels of connective tissue content (by wheat germ agglutinin staining). The authors hypothesized that severe burn trauma could induce myonuclear apoptosis along with increased SC activation, in order to counteract the loss of myonuclei. In brief, the major findings by Fry and colleagues were (summarized in Table 1): (1) burn trauma induces myonuclear and SC apoptosis, (2) SC content is decreased although the content of active SCs is increased in burn patients, and (3) the latter two are associa","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88317004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of resistance exercise‐induced muscle hypertrophy: ‘You can't make an omelette without breaking eggs’","authors":"Benoit Smeuninx, James McKendry","doi":"10.1113/JP273343","DOIUrl":"https://doi.org/10.1113/JP273343","url":null,"abstract":"It is well established that resistance exercise (RE) is a potent stimulus for skeletal muscle hypertrophy. As a result, a plethora of research has been directed towards unravelling the complexity of mechanisms driving these muscular changes in order to establish how RE training variables might best be manipulated to optimize phenotypic adaptations, with important implications for athletic performance and prevention of a myriad of negative health complications (e.g. sarcopenia, metabolic diseases and rheumatoidand osteoarthritis). Major breakthroughs in the field have arisen from studies utilizing the muscle biopsy technique and arteriovenous catheterization in conjunction with the infusion of one or multiple stable amino acid (AA) isotope tracers. Measuring the rate of appearance and/or disappearance of isotopic tracer(s) in various skeletal muscle protein sub-fractions (predominantly myofibrillar or sarcoplasmic) or across the artery–vein has demonstrated that skeletal muscle mass is regulated via temporal fluctuations in muscle protein synthesis (MPS) and muscle protein breakdown (MPB) (Atherton & Smith, 2012). Individuals undertaking RE in the postabsorptive state mount a robust increase in the acute MPS response alongside elevated MPB rates, such that net protein balance (NPB) remains negative. However, when an adequate amount of high-quality protein is consumed in close proximity to the RE bout, the MPS response is potentiated and a positive NPB is achieved. Over time, the accumulation of periods of positive NPB leads to skeletal muscle protein accretion, manifested as increased muscle fibre cross-sectional area and an increased muscle mass. Although we are slowly beginning to understand the principle molecular and metabolic mechanisms underpinning muscle hypertrophy, a lot is yet to be discovered. Acute stable AA isotope infusion trials to assess MPS and MPB have proven extremely insightful; however, this method is not without limitations. First, it is extremely difficult to measure the true precursor (labelled tRNA) when using the precursor–product approach to calculate fractional synthesis rate. Second, and perhaps more importantly, this approach does not offer the opportunity to assess MPS in a free-living environment over an extended period (e.g. over the course of a training regimen) as extended AA isotope infusions lead to participant discomfort and are extremely costly. These limitations are important as it has been reported that a discord exists between the MPS response to an acute bout of RE (at the onset of training) and the chronic muscle remodelling that occurs over the course of prolonged RE training, thought to be due to the limited window in which exercise-induced MPS rates can be captured using stable AA isotope tracer infusions (Mitchell et al. 2014). Circumventing these issues to increase RE research validity is critical in order to understand the complex relationship between temporal fluctuations in MPS and long-term musc","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87525655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced functional sympatholysis through endothelial signalling in healthy young men and women","authors":"S. Segal","doi":"10.1113/JP273454","DOIUrl":"https://doi.org/10.1113/JP273454","url":null,"abstract":"That the endothelium governs vasodilatation in healthy humans and animals is well established. Indeed, impaired endothelium-dependent dilatation (EDD) is diagnostic of vascular dysfunction. Through the generation of diffusible autacoids, e.g. nitric oxide (NO) and metabolites of arachidonic acid, an increase in luminal shear stress leads to relaxation of vascular smooth muscle and is integral to flow-dependent dilatation. In humans, manipulating arterial blood flow (i.e. shear stress) is a non-invasive diagnostic tool for evaluating endothelial function as vessel diameter and blood flow velocity are monitored using ultrasound. A second pathway for EDD involves the initiation of hyperpolarization by endothelial cells and the transmission of electrical charge through myoendothelial gap junctions to evoke smooth muscle relaxation (Bagher & Segal, 2011). While endothelium-dependent hyperpolarization (EDH) has been well characterized in small resistance arteries and arterioles of animals, there is a dearth of evidence for EDH in governing blood flow in humans. This gap in translating findings from animal studies to humans is attributable to the invasive nature of recording membrane potential in the vascular wall after surgical exposure. Thus, elucidating EDH signalling as a pathway for EDD in humans has been difficult. In this issue of The Journal of Physiology a new study by Hearon et al. (2016), applying mechanistic insight gleaned from animal models, has coupled clever experimental design with established protocols in human subjects to shed new light on a role for EDH in functional sympatholysis, i.e. the ability of exercising skeletal muscle to attenuate sympathetic vasoconstriction. By manipulating both the intensity of rhythmic handgrip contractions and signalling pathways for vasodilatation, Hearon and co-workers tested whether stimulating EDD – independent of NO and prostaglandins – enhanced the ability of active skeletal muscle to attenuate sympathetic vasoconstriction induced by α1-adrenoreceptor (α1AR) activation. Key to these experiments was the judicious application of agonists whose actions have been well defined using isolated vessel preparations in which membrane potential and calcium signalling were rigorously evaluated (Tran et al. 2012). Thus, as shown in resistance arteries, acetylcholine (ACh) stimulates the opening of smalland intermediate-conductance calcium-activated K+ channels (SKCa and IKCa, respectively) in endothelial cells to initiate hyperpolarization, which is transmitted directly (through myoendothelial gap junctions) into surrounding smooth muscle cells to promote vasodilatation (Crane et al. 2003). As the electrical signal is conducted along the endothelium, the vasodilator response is coordinated within the resistance network (Bagher & Segal, 2011). Studies of the microcirculation in anaesthetized hamsters have shown that conducted vasodilatation can attenuate sympathetic vasoconstriction (Kurjiaka & Segal, 1995) an","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78151672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}