The Japanese journal of physiology最新文献

{"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":"31 1","pages":""},"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":"521 1","pages":""},"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}

{"title":"Rac1 is a novel regulator of exercise‐induced glucose uptake","authors":"W. Peppler, R. MacPherson","doi":"10.1113/JP272929","DOIUrl":"https://doi.org/10.1113/JP272929","url":null,"abstract":"Exercise is widely known to lead to beneficial adaptions in whole body health, including improvements in indices of glucose homeostasis. During exercise, muscle contraction stimulates an increase in skeletal muscle glucose uptake in order to provide substrate for energy production. The provision of glucose to skeletal muscle is mediated by three factors: (1) the delivery of glucose to muscle; (2) the transport of glucose across the plasma membrane; and (3) the intracellular metabolism of glucose (Richter & Hargreaves, 2013). The delivery of glucose to working skeletal muscle is regulated by changes in blood flow and capillary recruitment, both of which increase with exercise. The transport of glucose across the plasma membrane is increased during exercise, which occurs by translocation of glucose transporter type 4 (GLUT4) from intracellular sites to the plasma membrane (sarcolemma and T-tubules), allowing for facilitated diffusion. Exercise increases the flux of glucose through glycolysis, and the enzyme hexokinase II (HKII) controls this process. Once inside the muscle cell, HKII phosphorylates glucose for commitment to glycolysis or for storage as glycogen. It is the coordination of delivery, transport and metabolism of glucose that leads to increases in glucose uptake during exercise (Richter & Hargreaves, 2013); however, the molecular mechanisms that mediate this process are not fully understood. Recently the Rho family GTPase Rac1 has emerged as having an important role in the regulation of skeletal muscle glucose uptake. Pioneering work from Drs Klip (JeBailey et al. 2004; Thong et al. 2007) and Ueda and Satoh (Ueda et al. 2010) revealed the role for Rac1 in this process, and a recent series of studies from Sylow and colleagues have further advanced our understanding. They found that Rac1 was required for insulin-induced ex vivo glucose uptake in murine soleus and extensor digitorum longus (EDL) muscles (Sylow et al. 2013a). Using pharmacological inhibition and an in vivo inducible muscle specific Rac1 knockout, they showed that Rac1 plays a critical role in electrically induced contraction-stimulated glucose transport (Sylow et al. 2013b). Finally, using a similar approach, they showed an attenuated response to stretch-induced glucose uptake in ex vivo soleus and EDL (Sylow et al. 2015). Despite this, the role of Rac1 in in vivo exercise-induced glucose uptake and GLUT4 translocation is not known. In a paper published in The Journal of Physiology, Sylow et al. (2016) demonstrate that Rac1 is a critical regulator of glucose uptake during exercise. To define the role of Rac1 in vivo, a Rac1 muscle-specific knockout (mKO) was established by breeding Rac1 floxed mice with mice carrying a muscle specific Cre recombinase. Rac1 mKO mice were induced at 10–14 weeks of age by a 3 week exposure to doxycycline in drinking water, followed by a 3 week washout period to reverse potential mitochondrial and gene expression changes induced by this treatme","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90014758","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":"Drugs and bugs: turning on the heat through UCP1 and UCP3","authors":"M. Harper","doi":"10.1113/JP273485","DOIUrl":"https://doi.org/10.1113/JP273485","url":null,"abstract":"The recent resurgence of biomedical interest in non-shivering thermogenesis has been fuelled by key discoveries, including the following: there is active brown adipose tissue (BAT) in adult humans; brown adipocytes and skeletal muscle cells have common cellular origins; and uncoupling protein-1 (UCP1)-expressing beige adipocytes emerge in white adipose tissue depots following stimulation, for example, by chronic cold exposure, exercise, or peroxisome proliferator-activated receptor-γ (PPARγ) agonists. While there has never been any question of the importance of UCP1 in thermogenesis, a role in this realm for UCP3 has not been clearly demonstrated. UCP1-deficient mice are cold-intolerant (Enerbäck et al. 1997), and develop obesity if housed at thermoneutrality (Feldmann et al. 2009). Shortly after the initial characterizations of the UCP1 knockout mouse, the UCP3 knockout mouse was produced and characterized. Given that UCP3 is expressed in brown adipose and skeletal muscle, it was anticipated that the UCP3 knockout mouse would have a number of physiological and metabolic deficiencies. Surprisingly the whole-body phenotypic characteristics unveiled were minimal, even though there was lower mitochondrial proton leak and increased oxidative stress in skeletal muscle. However, additional metabolic studies of UCP3 in vivo and in vitro revealed its roles in facilitating fatty acid oxidation and minimizing reactive oxygen species (ROS) emission (e.g. Bezaire et al. 2005), and indicated that UCP3 functions in a negative feedback loop in mitochondrial ROS emission (Echtay et al. 2003; Mailloux et al. 2011). Important in the interpretation of these findings is that UCP1 is expressed at exceptionally high levels ( 10% of mitochondrial protein) in BAT, a tissue that is ideally ‘poised’, both biochemically and anatomically, for thermoregulatory thermogenesis. In contrast, UCP3 is expressed at much lower levels in BAT and skeletal muscle, compared to UCP1 in BAT. Physiological thermogenic processes can be categorized as either obligatory or facultative. Obligatory forms are associated with the basal thermogenic processes occurring when the animal is resting in a post-absorptive and thermoneutral state. The latter comprise an animal’s basal metabolic rate. Another form of obligatory thermogenesis is the thermic effect of food. Facultative forms of thermogenesis are those associated with additional energy demanding functions (i.e. beyond the obligatory), and include shivering and non-shivering thermogenesis, non-exercise","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87206727","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":"Four‐week cold acclimation in adult humans shifts uncoupling thermogenesis from skeletal muscles to brown adipose tissue","authors":"D. Blondin, A. Daoud, T. Taylor, H. Tingelstad, V. Bézaire, D. Richard, A. Carpentier, A. W. Taylor, M. Harper, C. Aguer, F. Haman","doi":"10.1113/JP273395","DOIUrl":"https://doi.org/10.1113/JP273395","url":null,"abstract":"Muscle‐derived thermogenesis during acute cold exposure in humans consists of a combination of cold‐induced increases in skeletal muscle proton leak and shivering. Daily cold exposure results in an increase in brown adipose tissue oxidative capacity coupled with a decrease in the cold‐induced skeletal muscle proton leak and shivering intensity. Improved coupling between electromyography‐determined muscle activity and whole‐body heat production following cold acclimation suggests a maintenance of ATPase‐dependent thermogenesis and decrease in skeletal muscle ATPase independent thermogenesis. Although daily cold exposure did not change the fibre composition of the vastus lateralis, the fibre composition was a strong predictor of the shivering pattern evoked during acute cold exposure.","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"93 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74370559","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":"Vestibular feedback maintains reaching accuracy during body movement","authors":"Craig P Smith, R. Reynolds","doi":"10.1113/JP273125","DOIUrl":"https://doi.org/10.1113/JP273125","url":null,"abstract":"Reaching movements can be perturbed by vestibular input, but the function of this response is unclear. Here, we applied galvanic vestibular stimulation concurrently with real body movement while subjects maintained arm position either fixed in space or fixed with respect to their body. During the fixed‐in‐space conditions, galvanic vestibular stimulation caused large changes in arm trajectory consistent with a compensatory response to maintain upper‐limb accuracy in the face of body movement. Galvanic vestibular stimulation responses were absent during the body‐fixed task, demonstrating task dependency in vestibular control of the upper limb. The results suggest that the function of vestibular‐evoked arm movements is to maintain the accuracy of the upper limb during unpredictable body movement, but only when reaching in an earth‐fixed reference frame.","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"10 1","pages":"1339 - 1349"},"PeriodicalIF":0.0,"publicationDate":"2016-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84350920","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":"Reply from Pei‐Chi Yang, Jonathan D. Moreno, Mao‐Tsuen Jeng, Xander H. T. Wehrens, Sergei Noskov and Colleen E. Clancy","authors":"Pei-Chi Yang, J. Moreno, Mao-Tsuen Jeng, X. Wehrens, S. Noskov, C. Clancy","doi":"10.1113/JP273143","DOIUrl":"https://doi.org/10.1113/JP273143","url":null,"abstract":"We appreciate Williams et al. (2016) taking the time to comment on our recently published study (Yang et al. 2016). In their letter, the authors question the ‘usefulness’ of the computational modelling and simulation approaches that we used in part because as they state, ‘The blocking parameters used in Yang et al. (2016) are based on values reported in Hilliard et al. (2010) and subsequent publications from the same group.’ This statement does not reflect the careful process that we actually used in building our modelling approaches, where we rather considered the full range of experimentally measured IC50 values for flecainide interaction that have been reported in multiple studies. In addition to the assumption of IC50 = 0 μM (i.e. no interaction with RyR) as reported by the Williams group (Bannister et al. 2015), we reported the following in our paper (Yang et al. 2016): ‘Isoproterenol-stimulated Ca2+ waves in CASQ2 knockout (KO) CASQ2(−/−) mice were inhibited by flecainide with an IC50 of 2.0 ± 0.2 μM (Hwang et al. 2011), while other experimental preparations measured an IC50 range from 2 to 17 μM (Brunton et al. 2010; Hilliard et al. 2010; Hwang et al. 2011; Mehra et al. 2014) . . . We also predicted cases for variable flecainide IC50 = 3, 4, and 5 μM shown in Fig. 1.’ The model simulations led to the predictions that IC50 values above 5 μM are too low to show therapeutic benefit to normalize the catecholaminergic polymorphic ventricular tachycardia (CPVT) phenotype. An alternative interpretation is that the concentration of flecainide near the receptor is considerably higher than in the bulk water compartments, a possibility supported by our physics-based approach (Fig. 5 in Yang et al. 2016) that shows accumulation of flecainide on the membrane surface and very favourable conditions for neutral flecainide in the hydrophobic core of the membrane. Detailed investigations into membrane partitioning of drugs are ongoing in our group. The point of the simulations in our study was to make predictions about the necessary and sufficient targets of flecainide and the range of IC50 that would allow for normalization of the CPVT phenotype since the experimental literature has shown such variety in reported values. When we started the investigation reported in Yang et al. (2016), we had no preconceived intent or notion about the results. The predictions are the resulting outputs of the model, and suggest that Na+ channel block alone is not sufficient to prevent the CPVT phenotype. The critical point here is that the disparity in sensitivity of the dose–response for flecainide interaction with the RyR depends on the experimental approach being used. This issue has been the subject of discussion by others (Steele et al. 2013; Sikkel et al. 2013b; Smith & MacQuaide, 2015). Williams et al. describe their recent work in their letter. It is important to mention, however, the numerous other studies that report alternative data and explanations. Some in nati","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87516322","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":"Bile as a key aetiological factor of acute but not chronic pancreatitis: a possible theory revealed","authors":"P. Hegyi","doi":"10.1113/JP273108","DOIUrl":"https://doi.org/10.1113/JP273108","url":null,"abstract":"It has been known for more than a century that bile acids and gallstones may represent an aetiological factor in acute pancreatitis (AP). Importantly, while bile is responsible for around 40% of AP, its aetiological role in the chronic form of the disease (CP) is close to zero. Only 4% of patients suffering from CP have gallstones, and it is still not clear whether this is only an association or whether bile or gallstones play any pathophysiological role in the development of the chronic inflammation. In this issue of The Journal of Physiology, Ferdek et al. have offered the first explanation for this phenomenon at the cellular level (Ferdek et al. 2016). They have shown for the first time that bile acids elicit dramatic necrosis in pancreatic stellate cells (PSCs) but not in pancreatic acinar cells (PACs). In the presence of calcium, sodium cholate induces 73% necrosis in PSCs but only around 10% in PACs, suggesting that the PSC, the key player in the extracellular matrix in the pancreas, is the cell type most endangered by bile (Ferdek et al. 2016). Since the effects of bile acids on pancreatic ductal cells (PDCs) have also been characterized, the chronological events in how bile acids affect the exocrine pancreas and induce acute but not chronic pancreatitis can be followed (Fig. 1).","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90606399","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":"Mitochondrial‐derived vesicles: a new player in cardiac mitochondrial quality control","authors":"L. Bozi, Luiz R G Bechara, A. F. dos Santos, Juliane C Campos","doi":"10.1113/JP273124","DOIUrl":"https://doi.org/10.1113/JP273124","url":null,"abstract":"Mitochondria are critical organelles involved in adenosine triphosphate (ATP) synthesis, reactive oxygen species generation, ion homeostasis, aldehyde metabolism and programmed cell death. Loss of mitochondrial integrity is sufficient to establish pathological conditions such as cardiovascular diseases. In an attempt to ensure the maintenance of mitochondrial functionality, eukaryotic cells developed an integrated quality control system. This mitochondrial quality control machinery works in different levels of surveillance: (1) the antioxidant enzymes protect the organelle against oxygen-mediated toxicity, (2) the ubiquitin–proteasome system as well as the mitochondrial proteases and chaperones ensure the proteostasis by refolding or degrading damaged mitochondrial proteins, and (3) the interconnected processes of mitochondrial dynamics (fusion and fission) and mitophagy controls mitochondrial size, shape and clearance (Sugiura et al. 2014). More recently, a study by Cadete et al. (2016) published in The Journal of Physiology provides evidence that mitochondrial-derived vesicles (MDVs) are also involved in the maintenance of cardiac mitochondrial homeostasis. Although the results are associative, the well-conducted experiments complemented by the relevant findings make this work attractive, opening a new field of investigation in cardiac mitochondrial physiology. MDVs are generated by selective incorporation of mitochondrial cargo into small vesicles (70–150 nm of diameter) which transit to the lysosome for subsequent degradation (Sugiura et al. 2014). Despite it being a conserved mechanism from bacteria to mammals, the presence of MDVs and their physiological relevance in various cells types, including cardiomyocytes, needs to be clarified. In an attempt to characterize the role of MDVs in heart physiology, Cadete et al. (2016) used both in vitro and in vivo approaches. The authors first showed the presence of MDVs in H9C2 myoblasts (a cardiac cell line). It is worth mentioning that their innovative approach of switching the cell energy substrate from glucose to galactose, in order to stimulate the mitochondrial metabolism, helped the authors to identify MDVs under normal conditions. MDVs were identified by their apparent size and selective enrichment for mitochondrial markers from both matrix (PDH – pyruvate dehydrogenase) and outer membrane (TOM20 – translocase of the outer membrane) at baseline. A further increase in MDVs along with a hyperfused mitochondrial network was detected upon mild oxidative stress. Under severe oxidative stress myoblasts accumulated both PDH-enriched vesicles and fragmented mitochondria. Using another stress condition, authors demonstrated that doxorubicin-induced stress increased MDV formation within 30 min without affecting mitochondrial morphology and bioenergetics in myoblasts. Interestingly, PDH and TOM20-enriched vesicles gradually declined in the following 6 h, while the mitochondrial network became fragmented","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"133 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75989310","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":"Membrane‐associated guanylate kinase dynamics reveal regional and developmental specificity of synapse stability","authors":"Jonathan M. Levy, R. Nicoll","doi":"10.1113/JP273147","DOIUrl":"https://doi.org/10.1113/JP273147","url":null,"abstract":"The membrane‐associated guanylate kinase (MAGUK) family of synaptic scaffolding proteins anchor glutamate receptors at CNS synapses. MAGUK removal via RNAi‐mediated knockdown in the CA1 hippocampal region in immature animals causes rapid and lasting reductions in glutamatergic transmission. In mature animals, the same manipulation has little acute effect. The hippocampal dentate gyrus, a region with ongoing adult neurogenesis, is sensitive to MAGUK loss in mature animals, behaving like an immature CA1. Over long time courses, removal of MAGUKs in CA1 causes reductions in glutamatergic transmission, indicating that synapses in mature animals require MAGUKs for anchoring glutamate receptors, but are much more stable. These results demonstrate regional and developmental control of synapse stability and suggest the existence of a sensitive period of heightened hippocampal plasticity in CA1 of pre‐adolescent rodents, and in dentate gyrus throughout maturity.","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83653513","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}