Journal of Physiology-London最新文献

{"title":"Physiology of ageing skeletal muscle and the protective effects of exercise","authors":"Christopher W. Sundberg","doi":"10.1113/JP287926","DOIUrl":"10.1113/JP287926","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 1","pages":"3-6"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Timing is everything: complex (a)synchrony of heart-muscle interactions during exercise.","authors":"Sean P Langan","doi":"10.1113/JP287967","DOIUrl":"https://doi.org/10.1113/JP287967","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An α7 nicotinic and GABAB receptor-mediated pathway controls acetylcholine release in the tripartite neuromuscular junction","authors":"Konstantin Petrov,&nbsp;Oksana Lenina,&nbsp;Jacqueline Leroy,&nbsp;Véronique Bernard,&nbsp;Thibaut Germain,&nbsp;Charles Truong,&nbsp;Leniz Nurullin,&nbsp;Guzel Sibgatullina,&nbsp;Kinji Ohno,&nbsp;Dmitry Samigullin,&nbsp;Eric Krejci","doi":"10.1113/JP287243","DOIUrl":"10.1113/JP287243","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <div>Terminal Schwann cells (TSCs) are capable of regulating acetylcholine (ACh) release at the neuromuscular junction (NMJ). We have identified GABA as a gliotransmitter at mouse NMJs. When ACh activates α7 nicotinic ACh receptor (nAChRs) on TSCs, GABA is released and activates GABA_B receptors on the nerve terminal that subsequently reduce ACh release. Indeed, specific deletion of the α7 nAChR in TSCs or inhibition of the metabotropic GABA_B receptor prevents the reduction in the quantal content of the end-plate potential induced by cholinesterase inhibitors. The α7/GABA_B receptor-mediated pathway is activated when ACh that escapes from collagen Q (ColQ) anchored AChE in the synaptic cleft and from PRiMA-anchored butyrylcholinesterase on the TSC activates α7 nAChRs on the TSC. Consequently, prolonged tetanic stimulation of isolated muscle activates the α7/GABA_B receptor pathway, which reduces post-tetanic ACh release. When AChE levels are low in neonatal mice, the α7/GABA_B receptor-mediated pathway decreases ACh release and reduces <i>ex vivo</i> muscle fatigue. For ColQ-deficient mice where AChE is not clustered, the decrease in AСh release following activation of this pathway contributes to mouse fatigue <i>in vivo</i>.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </div>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Key points</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Acetylcholine (ACh) released from the nerve terminal at the neuromuscular junction (NMJ) can activate α7 nicotinic ACh receptor (nAChR) on terminal Schwann cells, releasing gamma-aminobutyric acid (GABA) that activates metabotropic GABA_B receptors on the nerve terminal which then reduces further ACh release from the nerve.</li>\u0000 \u0000 <li>At the mature NMJ, before reaching α7 nAChRs on terminal Schwann cells ACh is normally hydrolyzed by AChE clustered in the synaptic cleft and by BChE anchored to the TSC.</li>\u0000 \u0000 <li>ACh can activate the α7/GABAB receptor-mediated pathway and depress subsequent ACh release when AChE at the NMJ is low, either during development or in congenital myasthenic syndrome. In the latter case, this pathway contributes to muscle fatigue.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 2","pages":"507-527"},"PeriodicalIF":4.7,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mechanisms of electrical neuromodulation","authors":"Gustavo Balbinot,&nbsp;Matija Milosevic,&nbsp;Cindi M. Morshead,&nbsp;Stephanie N. Iwasa,&nbsp;Jose Zariffa,&nbsp;Luka Milosevic,&nbsp;Taufik A. Valiante,&nbsp;Joaquín Andrés Hoffer,&nbsp;Milos R. Popovic","doi":"10.1113/JP286205","DOIUrl":"10.1113/JP286205","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <div>The central and peripheral nervous systems are specialized to conduct electrical currents that underlie behaviour. When this multidimensional electrical system is disrupted by degeneration, damage, or disuse, externally applied electrical currents may act to modulate neural structures and provide therapeutic benefit. The administration of electrical stimulation can exert precise and multi-faceted effects at cellular, circuit and systems levels to restore or enhance the functionality of the central nervous system by providing an access route to target specific cells, fibres of passage, neurotransmitter systems, and/or afferent/efferent communication to enable positive changes in behaviour. Here we examine the neural mechanisms that are thought to underlie the therapeutic effects seen with current neuromodulation technologies. To gain further insights into the mechanisms associated with electrical stimulation, we summarize recent findings from genetic dissection studies conducted in animal models.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </div>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Key points</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Electricity is everywhere around us and is essential for how our nerves communicate within our bodies.</li>\u0000 \u0000 <li>When nerves are damaged or not working properly, using exogenous electricity can help improve their function at distinct levels – inside individual cells, within neural circuits, and across entire systems.</li>\u0000 \u0000 <li>This method can be tailored to target specific types of cells, nerve fibres, neurotransmitters and communication pathways, offering significant therapeutic potential.</li>\u0000 \u0000 <li>This overview explains how exogenous electricity affects nerve function and its potential benefits, based on research in animal studies.</li>\u0000 \u0000 <li>Understanding these effects is important because electrical neuromodulation plays a key role in medical treatments for neurological conditions.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 2","pages":"247-284"},"PeriodicalIF":4.7,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1113/JP286205","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chloride reported missing from brain and extracellular matrix is a suspect","authors":"Charles Nicholson","doi":"10.1113/JP288074","DOIUrl":"10.1113/JP288074","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 2","pages":"245-246"},"PeriodicalIF":4.7,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142899958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of pericardium on ventricular mechanical interdependence in an isolated biventricular working pig heart model","authors":"Fanny Vaillant,&nbsp;Emma Abell,&nbsp;Laura R. Bear,&nbsp;Guido Caluori,&nbsp;Charly Belterman,&nbsp;Ruben Coronel,&nbsp;Sylvain Ploux,&nbsp;Pierre Dos Santos","doi":"10.1113/JP286259","DOIUrl":"10.1113/JP286259","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 \u0000 &lt;div&gt;The pericardium plays an important role in mechanical interactions between the right (RV) and left (LV) ventricles, referred to as ventricular interdependence. However, the exact mechanisms of its supportive role remain unknown. The present study aimed to evaluate specifically ventricular interdependence in a model of isolated biventricular working heart of large mammal, which is in absence of neurohormonal influence or series interactions, and to evaluate the impacts of intact pericardium on this phenomenon. Pig hearts were excised with the pericardium intact and connected to a biventricular working mode setup. Low and high ventricular preloads and afterloads were imposed on the hearts by changing independently the left (LA) and right (RA) atrial pressures, or the aortic (Ao) and pulmonary artery (PA) pressures, respectively, in the presence or absence of an intact pericardium. In the presence of the pericardium, increasing atrial pressures mainly impacted the ipsilateral ventricular haemodynamics, including an increase in ventricular outflow and end-diastolic pressures, independent of the contralateral atrial pressure. LV haemodynamics were also mainly altered by the increase in the ipsilateral afterload (Ao pressure). By contrast, RV haemodynamics, including the PA flow, were not only affected by increasing its ipsilateral (PA pressure), but also by its contralateral (Ao pressure) ventricular afterload. The preload but not afterload-dependent effects were abolished after removing the pericardium. Our work indicates that RV haemodynamics are highly impacted by the pericardiectomy. This highlights the requirement of keeping the pericardium intact to explore accurately cardiac haemodynamics, particularly in the RV.\u0000\u0000 &lt;figure&gt;\u0000 &lt;div&gt;&lt;picture&gt;\u0000 &lt;source&gt;&lt;/source&gt;&lt;/picture&gt;&lt;p&gt;&lt;/p&gt;\u0000 &lt;/div&gt;\u0000 &lt;/figure&gt;\u0000 &lt;/div&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Key points&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ul&gt;\u0000 \u0000 &lt;li&gt;Pericardium has an important role in maintaining mechanical interventricular interaction, even if it is not essential for life.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;We used an &lt;i&gt;ex vivo&lt;/i&gt; biventricular working pig heart model to explore intrinsic ventricular responses to independent variations of left and right preload and afterload, in the presence and absence of the pericardium.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;We show that, in the presence of the pericardium, the right ventricular haemodynamics is impacted by the ipsilateral preload as well as the ipsi- and contralateral afterloads, whereas the left ventricular haemodynamics is only impacted by its ipsilateral pre- and afterload.&lt;/li&gt;\u0000 ","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 2","pages":"285-300"},"PeriodicalIF":4.7,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Divergent selection for basal metabolic rate in mice affects the abundance of UCP1 protein: implications for translational studies","authors":"Paweł Brzęk,&nbsp;Piotr Selewestruk,&nbsp;Julita Sadowska,&nbsp;Andrzej K. Gębczyński,&nbsp;Aneta Książek,&nbsp;Anastasia Kalinovich,&nbsp;Jan Nedergaard,&nbsp;Marek Konarzewski","doi":"10.1113/JP286669","DOIUrl":"10.1113/JP286669","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 \u0000 &lt;div&gt;Low basal metabolic rate (BMR) is a risk factor for obesity, whereas elevation of non-shivering thermogenesis (NST) is a promising means to combat obesity. Because heat generated by NST covers thermogenic needs not fulfilled by BMR, one can expect the presence of a negative relationship between both parameters. Understanding of the mechanisms underlying this relationship is therefore important for interpretation of the results of translational experiments and the development of anti-obesity treatments. We studied two lines of laboratory mice divergently selected for high or low level of BMR, raised at 23°C and subsequently acclimated to different ambient temperatures (30, 23 and 4°C). Mice selected for low BMR accumulated more fat but simultaneously showed higher NST capacity and more uncoupling protein-1 (UCP1) in interscapular brown adipose tissue (iBAT), to compensate for their lower heat production through BMR. The between-line difference in UCP1 protein abundance was significant even in mice acclimated to 30°C when the level of UCP1 is very low. Differences in NST capacity between selected lines and acclimation temperatures were explained by UCP1 iBAT abundance. Our results reveal that BMR is inversely correlated with UCP1 protein abundance and NST, even after acclimation to thermoneutrality. Thus, low values of BMR can increase both obesity risk and the magnitude of NST, i.e. the process whose activation has been proposed to mitigate obesity risk. All these effects should be taken into account in the design and interpretation of translational studies on mice models of metabolic diseases.\u0000\u0000 &lt;figure&gt;\u0000 &lt;div&gt;&lt;picture&gt;\u0000 &lt;source&gt;&lt;/source&gt;&lt;/picture&gt;&lt;p&gt;&lt;/p&gt;\u0000 &lt;/div&gt;\u0000 &lt;/figure&gt;\u0000 &lt;/div&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Key points&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ul&gt;\u0000 \u0000 &lt;li&gt;Basal metabolic rate (BMR) and non-shivering thermogenesis (NST) based on the activity of uncoupling protein-1 (UCP1) are two main sources of heat in laboratory mice.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Both BMR and UCP1 can affect obesity risk in laboratory rodents and humans.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Here we studied BMR, NST, and the abundance of UCP1 in laboratory mice selected divergently towards either high or low BMR.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;We showed that BMR is negatively correlated with UCP1 abundance and this effect is not removed even after acclimation to thermoneutrality.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;The pattern described reveals that BMR can affect not only obesity risk but also the magnitude of UCP1-mediated NST. Since activation of NST was proposed to mitigate obesity risk, variation in BMR should be taken into account in tra","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 2","pages":"319-336"},"PeriodicalIF":4.7,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heartificial intelligence: smart solutions for CHF: An A(I)MT approach.","authors":"Samuel Gillman, Irving H Zucker, Han-Jun Wang","doi":"10.1113/JP287953","DOIUrl":"https://doi.org/10.1113/JP287953","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Excessive hypercholesterolaemia during pregnancy as a risk factor for endothelial dysfunction in pre-eclampsia.","authors":"Amanda A de Oliveira, Floor Spaans, Christy-Lynn M Cooke, Sandra T Davidge","doi":"10.1113/JP285943","DOIUrl":"https://doi.org/10.1113/JP285943","url":null,"abstract":"<p><p>Pregnancy induces significant changes in the maternal cardiovascular system, and insufficient vascular endothelial adaptations to pregnancy contribute to the development of pregnancy complications such as pre-eclampsia. Pre-eclampsia is not only a major cause of maternal morbidity and mortality, but also a significant risk factor for the development of later-life cardiovascular disease. However, the specific mechanisms underlying the pathophysiology of pre-eclampsia, as well as the mechanisms for an increased susceptibility to cardiovascular disease later in life, are not fully characterized. In this review, we discuss the concept that excessive pregnancy-specific dyslipidaemia, particularly hypercholesterolaemia, is a significant risk factor for the development of pre-eclampsia. We further outline novel potential mechanisms (i.e. oxidized low-density lipoprotein receptor 1 and toll-like receptor 4) underlying endothelial dysfunction induced by excessively high cholesterol levels during pregnancy (in the context of pre-eclampsia), in addition to discussing the overall implications of having had a pregnancy complicated by pre-eclampsia on later-life maternal vascular health. Determining the mechanisms by which excessive, pregnancy-specific dyslipidaemia/hypercholesterolaemia impact maternal endothelial health in pregnancy, and later in life, will create a window of opportunity to diagnose and develop targeted therapy for a susceptible population of women, aiming to ultimately reduce the societal burden of cardiovascular disease.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in the cortical GABAergic inhibitory system with ageing and ageing-related neurodegenerative diseases.","authors":"Wolfgang Taube, Benedikt Lauber","doi":"10.1113/JP285656","DOIUrl":"https://doi.org/10.1113/JP285656","url":null,"abstract":"<p><p>The human cortical inhibitory system is known to play a vital role for normal brain development, function, and plasticity. GABA is the most prominent inhibitory neurotransmitter in the CNS and is a key regulator not only for motor control and motor learning, but also for cognitive processes. With ageing and many neurodegenerative pathologies, a decline in GABAergic function in several cortical regions together with a reduced ability to task-specifically modulate and increase inhibition in the primary motor cortex has been observed. This decline in intracortical inhibition is associated with impaired motor control but also with diminished motor-cognitive (i.e. dual-tasking) and cognitive performance (e.g. executive functions). Furthermore, more general well-being such as sleep quality, stress resistance or non-specific pain perception are also associated with reduced GABA functioning. The current review highlights the interplay between changes in GABAergic function and changes in motor control, motor-cognitive and cognitive performance associated with healthy ageing, as well as in seniors with neurodegenerative diseases such as mild cognitive impairment. Furthermore, recent evidence highlighting the ability to up- or downregulate cortical inhibition by means of physical exercise programs is presented and discussed.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142899955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}