The Japanese journal of physiology最新文献

{"title":"Short‐term exercise‐induced protection of cardiovascular function and health: why and how fast does the heart benefit from exercise?","authors":"D. Thijssen, L. Uthman, Yasina B. Somani, N. van Royen","doi":"10.1113/JP282000","DOIUrl":"https://doi.org/10.1113/JP282000","url":null,"abstract":"Regular exercise training has potent and powerful protective effects against the development of cardiovascular disease. These cardioprotective effects of regular exercise training are partly explained through the effects of exercise on traditional cardiovascular risk factors and improvement in cardiac and vascular health, which take several weeks to months to develop. This review focuses on the observation that single bouts of exercise may also possess an underrecognized, clinically useful form of immediate cardioprotection. Studies, performed in both animals and humans, demonstrate that single or short‐term exercise‐induced protection (SEP) attenuates the magnitude of cardiac and/or vascular damage in response to prolonged ischaemia and reperfusion injury. This review highlights preclinical evidence supporting the hypothesis that SEP activates multiple pathways to confer immediate protection against ischaemic events, reduce the severity of potentially lethal ischaemic myocardial injury, and therefore act as a physiological first line of defence against injury. Given the fact that the extent of SEP could be modulated by exercise‐related and subject‐related factors, it is important to recognize and consider these factors to optimize future clinical implications of SEP. This review also summarizes potential effector signalling pathways (i.e. communication between exercising muscles to vascular/cardiac tissue) and intracellular pathways (i.e. reducing tissue damage) that ultimately confer protection against cardiac and vascular injury. Finally, we discuss potential future directions for designing adequate human and animal studies that will support developing effective SEP strategies for the (multi‐)diseased and aged individual.","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"1228 1","pages":"1339 - 1355"},"PeriodicalIF":0.0,"publicationDate":"2021-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85236955","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":"Ion Channels","authors":"D. Lipscombe, C. Toro","doi":"10.1113/jphysiol.1997.sp021990","DOIUrl":"https://doi.org/10.1113/jphysiol.1997.sp021990","url":null,"abstract":"","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80845268","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":"Location, location, location: lessons from airway epithelial anion channels","authors":"L. Delpiano, M. Gray","doi":"10.1113/JP279125","DOIUrl":"https://doi.org/10.1113/JP279125","url":null,"abstract":"Keeping our lungs healthy is a challenging job as every breath we take exposes our airways to myriad pathogenic organisms. The conducting airways have evolved a sophisticated system that prevents this by first capturing the nasty bugs in a sea of mucus and then propelling the entrapped microorganisms upwards towards the mouth, where they are either swallowed or spat out. The removal of the bug-laden mucus by mucociliary clearance (MCC) is a key process and the first line of defence against inhaled pathogens (Saint-Criq & Gray, 2017). Reduction in MCC leads to airway disease such as cystic fibrosis (CF). Here, dysfunction in the apically located CFTR chloride channel causes a severe reduction in the airways’ surface hydration. This makes the mucus very sticky and difficult to move, resulting in MCC failure and eventual chronic lung-destroying infections. While CFTR is clearly essential for MCC, there are other chloride channels that provide a partial back-up to CFTR. The most well studied is the calcium-activated chloride channel (CaCC), which is switched on by a rise in cytosolic calcium, conventionally caused by G-protein-coupled receptor agonists such as nucleotides and acetylcholine (Saint-Criq & Gray, 2017). For many years the identity of the airway CaCC was unknown until three papers in 2008 discovered that the TMEM16A gene encodes a CaCC which is expressed in airway epithelial cells, as well as many other cell types (Kunzelmann et al. 2019). These papers were the catalyst that led to a much better understanding of how the channel works at an atomic level as well as furthering our understanding of the physiological function of TMEM16A in diverse tissues, including epithelial, sensory and muscle (Kunzelmann et al. 2019). Not surprisingly, scientists realised the potential of TMEM16A as a target for treating important human disease such as CF, asthma, hypertension and gastrointestinal motility disorders. Several groups have reported the identification of ‘specific’ small molecule activators and potentiators, as well as a plethora of putative inhibitors of TMEM16A (Kunzelmann et al. 2019). One such TMEM16A modulator, known as Eact, was identified by the Verkman group back in 2011. This compound was shown to stimulate TMEM16A without changing cytosolic calcium and therefore thought to be a bone fide TMEM16A activator. Since then, several groups have reported conflicting results, either that Eact failed to activate TMEM16A, or that it activated TMEM16A, but this was due to an Eact-induced increase in cytosolic calcium. The paper in this issue of The Journal of Physiology by Genovese et al. (2019) has shed new light on the ‘Eact/TMEM16A conundrum’, and provides a very nice physiological explanation for these apparent discrepancies. The authors found that the response to Eact was cell model dependent. In cell lines expressing TMEM16A, Eact activated the channel. However, in fully differentiated airway epithelial cultures, Eact failed to activate TM","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"114 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82441497","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":"Home exercise reduces cardiometabolic disease risk","authors":"Cesar A Meza","doi":"10.1113/JP278934","DOIUrl":"https://doi.org/10.1113/JP278934","url":null,"abstract":"Obesity and a sedentary lifestyle are major contributors to poor metabolic and vascular health. As such, there has been a focus towards understanding the mechanisms underlying improvements in health related to physical activity. However, there remains a need for strategies that encourage patients to perform exercise independently and outside of the laboratory-supervised research setting. Investigations into skeletal muscle microvasculature function can provide insight into the links between cardiovascular and metabolic health. Increased nitric oxide (NO) production via endothelial NO synthase (eNOS) promotes muscle capillary recruitment to increase insulin-stimulated glucose uptake (Vincent et al. 2004). However, the levels of bioavailable NO are reduced in obesity due to quenching by oxidants, such as superoxide. NADPH oxidase (NOX) complexes are predominant sources of superoxide in the endothelium of obese individuals; therefore, the relative activation of eNOS versus NOX may provide an indication of microvascular function. In a recent issue of The Journal of Physiology, Scott et al. (2019) investigated whether home-based exercise can mitigate insulin resistance and vascular dysfunction while eliminating potential barriers of exercise adherence, such as access to facilities. Thirty-two males and females (age 36 ± 10 years) with an elevated risk of developing cardiovascular disease (body mass index 34.3 ± 5 kg/m; V̇O2peak 24.6 5.7 ml/kg/min) performed 12 weeks of exercise training under one of the following conditions: home-based high-intensity interval training (Home-HIT; n = 9), laboratory-based supervised HIT (Lab-HIT; n = 10) or home-based moderate-intensity continuous training (Home-MICT; n = 13). The participants who performed home-based exercise were ‘virtually supervised’ using a heart rate monitor, and instructed to achieve 80% or 65% of predicted heart rate maximum (HRmax 220 – age) during the intervals or continuous exercise, respectively. The home-based and laboratory-supervised HIT exercise sessions consisted of 1-min bouts of exercise interspersed with 1 min of rest. The Home-MICT group was instructed to perform continuous exercise of either swimming, cycling or walking/running. Participants in each group trained three times per week. To monitor adherence to exercise prescription, HR data obtained from the HR monitors were automatically uploaded to a cloud storage site (www.flow.polar.com) after each session. Endothelial function and aortic stiffness were assessed via flow-mediated dilatation (FMD) and pulse wave velocity (PWV), respectively. Insulin sensitivity was measured using an oral glucose tolerance test (OGTT). Lastly, a resting muscle biopsy was collected to measure markers of metabolic and vascular function via immunofluorescence. The primary finding was that the improvements in endothelium-dependent dilatation, aortic stiffness and insulin sensitivity were comparable between home-based exercise groups and laboratory-supe","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"73 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89895318","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":"Non‐synergistic synergies of muscle activation: an apparent oxymoron","authors":"F. Lacquaniti, F. Sylos-Labini, M. Zago","doi":"10.1113/JP279111","DOIUrl":"https://doi.org/10.1113/JP279111","url":null,"abstract":"Non-synergistic synergies of muscle activation: an apparent oxymoron Francesco Lacquaniti , Francesca Sylos-Labini and Myrka Zago Department of Systems Medicine and Center of Space BioMedicine of the University of Rome Tor Vergata, Rome, Italy Laboratory of Neuromotor Physiology of the IRCCS Santa Lucia Foundation, Rome, Italy Department of Civil Engineering and Computer Science Engineering and Centre of Space Biomedicine of the University of Rome Tor Vergata, Rome, Italy","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77784197","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":"In Memoriam: Paul M. Vanhoutte.","authors":"M. Barton, C. Cardillo","doi":"10.1113/JP279124","DOIUrl":"https://doi.org/10.1113/JP279124","url":null,"abstract":"On 23 August 2019, science lost one of its great minds: Paul Michel Georges Remi Vanhoutte, born on 26 November 1940 in Merelbeke near Ghent in Belgium, unexpectedly died in Paris after he had suffered a fall 10 days earlier. He was ‘one of the fathers of vascular biology’ (Heistad, 2008) who contributed to and shaped our understanding of how vascular endothelial cells regulate blood flow under physiological conditions and in disease.","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"183 1","pages":"5731-5737"},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83454523","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":"Ion channels: the concept emerges","authors":"Angus M. Brown","doi":"10.1113/JP279059","DOIUrl":"https://doi.org/10.1113/JP279059","url":null,"abstract":"The belief that the broad sweep of the Hodgkin–Huxley papers (Hodgkin & Huxley, 1952a,c,e,f Hodgkin et al. 1952) can be adequately summarised within a standard textbook chapter is fanciful at best and disingenuous at worst, because such summaries consist of scientific sound-bites that deprive students of the big picture; how decisive experiments create a linear narrative culminating in an internally consistent piece of work. In textbook chapters devoted to Hodgkin and Huxley’s work there are two topics that are inevitably omitted. The first is the separation of the trans-membrane current into INa and IK, the process usually described as a simple subtraction of currents recorded in Na+-free seawater from control currents, which is a gross simplification that neglects to recognise Hodgkin and Huxley’s elegant mathematical solution to the problem (Hodgkin & Huxley, 1952c). Fortunately there exists a superb account of this subject (Cronin, 1987). The second topic, and the subject of this editorial, relates to whether ion movements across a membrane conform to the independence principle. This principle, which was universally accepted at the time, derived from the equations of Teorell and Ussing, and described how the probability of the movement of ions across membranes was under the influence of electrical and chemical gradients but was independent of the presence of other ions (Teorell, 1949; Ussing, 1949). This topic appears deceptively simple upon initial inspection but consideration of the underlying mathematical foundations reveals unexpected complexity. Consider a cell bathed in saline where the influx of a particular ion can be expressed as","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89727427","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":"Changing perspectives on how the permeation pathway through potassium channels is regulated","authors":"K. A. Black, Ruitao Jin, Sitong He, J. Gulbis","doi":"10.1113/JP278682","DOIUrl":"https://doi.org/10.1113/JP278682","url":null,"abstract":"The primary means by which ion permeation through potassium channels is controlled, and the key to selective intervention in a range of pathophysiological conditions, is the process by which channels switch between non‐conducting and conducting states. Conventionally, this has been explained by a steric mechanism in which the pore alternates between two conformations: a ‘closed’ state in which the conduction pathway is occluded and an ‘open’ state in which the pathway is sufficiently wide to accommodate fully hydrated ions. Recently, however, ‘non‐canonical’ mechanisms have been proposed for some classes of K+ channels. The purpose of this review is to illuminate structural and dynamic relationships underpinning permeation control in K+ channels, indicating where additional data might resolve some of the remaining issues.","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88123376","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":"Measuring blood flow through intrapulmonary and intracardiac shunts: a technical labyrinth","authors":"G. Foster","doi":"10.1113/JP278820","DOIUrl":"https://doi.org/10.1113/JP278820","url":null,"abstract":"Intracardiac and intrapulmonary pathways permitting the right-to-left shunting of venous blood can impair pulmonary gas exchange efficiency and provide passageways for the arterialization of venous blood clots. Intrapulmonary arteriovenous anastomoses (IPAVAs) are recruited with increasing exercise intensity, acute hypoxia, and when cardiac output is increased by physiological or pharmacological stress. Whether IPAVA recruitment is sufficient in magnitude to impair pulmonary gas exchange efficiency has been a matter of great debate. As with most fields of research, settling this debate probably requires the development of novel methodology. In this case, methodology is needed to permit the accurate measurement of blood flow and gas exchange through shunt pathways that may be susceptible to pre-capillary gas exchange. This is a void remaining to be filled; yet, several tools have been used separately to approximate blood flow through IPAVAs or gas exchange deficits due to shunt. Measuring blood flow through either pathway is technically challenging and typically relies on the lung’s ability to filter blood. It is reasoned that if particles larger in diameter than the pulmonary capillaries are injected into a peripheral vein and subsequently observed in the systemic arterial circulation, they must have travelled by way of cardiac or pulmonary shunt. In animal models, solid 25-μm-diameter microspheres can be injected into a peripheral vein and physically collected in the arterial circulation. Anatomical shunt fraction can be calculated using the fraction of microspheres collected and measures of cardiac output. In humans, shunt fraction can be assessed by injecting radiolabelled macroaggregates and using nuclear medicine to count the particles that have bypassed the lung. Agitated saline contrast echocardiography, another approach, uses a mixture of small air bubbles injected into a peripheral vein; detection of saline contrast in the left ventricle is a sure sign of intracardiac or intrapulmonary shunt. Saline contrast is more feasible, and, therefore, frequently used in humans, but it provides little detail with respect to the magnitude of shunted blood owing to methodological limitations (Hackett et al. 2016; Boulet et al. 2017). Finally, the multiple inert gas elimination technique (MIGET) provides an assessment of gas exchange through the infusion of six inert gases of varying blood solubilities. Measurements of gas retained in the blood and excreted from the lung are mathematically modelled to approximate the lung’s ventilation– perfusion distribution, including an estimated shunt fraction. MIGET is a highly complex technique successfully used by just a few worldwide. In this issue of The Journal of Physiology, Stickland et al (2019) conducted a highly technical study involving the combination of three techniques for measuring intracardiac/intrapulmonary shunt in anaesthetized canines. Measurements were made at rest, with dopamine and dobutami","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76653949","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":"New molecular motif contributes to NKCC2 trafficking","authors":"Keyona N King-Medina, Cesar A Romero","doi":"10.1113/JP278896","DOIUrl":"https://doi.org/10.1113/JP278896","url":null,"abstract":"One of the most important functions of the kidney is the formation of urine and the maintenance of electrolyte and water homeostasis. The Na+–K+–2Cl− cotransporter (NKCC2) is a major contributor to this process by actively reabsorbing Na+, K+ and Cl− in the kidney’s loop of Henle. The properties of this transporter are the subject of a recent article in The Journal of Physiology by Marcoux et al. (2019) in which they report that variants of this protein alter trafficking of NKCC2, which ultimately influences the reabsorption of sodium chloride (NaCl) along the thick ascending limb of the loop of Henle (TAL). The TAL is one segment of the nephron and is of particular interest since approximately 25% of the Na+ in the glomerular filtrate is reabsorbed from it back into the circulation (Castrop & Schnermann, 2008; Ares et al. 2011; Marcoux et al. 2019). The magnitude of the reabsorption implies that this segment (and NKCC2) is important in the control of blood pressure and total body sodium homeostasis. In humans, NKCC2 is the major determinant of ion movement from the lumen of the TAL, across the tubular epithelium and back into the blood. NKCC2 is a membrane protein that has 12 transmembrane (TM) domains and a large intracellular loop near the middle of the molecule, a structure that is similar to other related membrane ion transporters","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88068977","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}