Journal of Physiology-London最新文献

{"title":"Enhanced inhibitory input to triceps brachii in humans with spinal cord injury","authors":"Carley L. P. Butler, Sina Sangari, Bing Chen, Monica A. Perez","doi":"10.1113/JP285510","DOIUrl":"10.1113/JP285510","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <div>Most individuals with cervical spinal cord injury (SCI) show increased muscle weakness in the elbow extensor compared to elbow flexor muscles. Although this is a well-known functional deficit, the underlying neural mechanisms remain poorly understood. To address this question, we measured the suppression of voluntary electromyographic activity (svEMG; a measurement thought to reflect changes in intracortical inhibition) by applying low-intensity transcranial magnetic stimulation over the arm representation of the primary motor cortex during 10% of isometric maximal voluntary contraction (MVC) into elbow flexion or extension in individuals with and without chronic cervical SCI. We found that the svEMG latency and duration were not different between the biceps and triceps brachii in controls but prolonged in the triceps in individuals with SCI. The svEMG area was larger in the triceps compared to the biceps in both groups and further increased in SCI participants, suggesting a pronounced intracortical inhibitory input during elbow extension. A negative correlation was found between svEMG area and MVCs indicating that control and SCI participants with lower svEMG area had larger MVCs. The svEMG area was not different between 5% and 30% of MVC, making it less probable that differences in muscle strength between groups contributed to our results. These findings support the existence of strong inhibitory input to corticospinal projections controlling elbow extensor compared to flexor muscles, which is more pronounced after chronic cervical SCI.\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>After cervical spinal cord injury (SCI), people often recover function in elbow flexor, but much less in elbow extensor muscles. The neural mechanisms contributing to this difference remain unknown.</li>\u0000 \u0000 <li>We measured the suppression of voluntary electromyographic activity (svEMG) elicited through low-intensity transcranial magnetic stimulation of the primary motor cortex (assumed to reflect changes in intracortical inhibition) in the biceps and triceps muscles in controls and individuals with cervical chronic incomplete SCI.</li>\u0000 \u0000 <li>We found increased svEMG area in the triceps compared to the biceps in controls and SCI participants, with this measurement being even more pronounced in the triceps after SCI. The svEMG area correlated with maximal voluntary contraction values in both groups, suggesting the people with lesser inhibition had larger motor output.</li>\u0000 \u0000 ","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"602 24","pages":"6909-6923"},"PeriodicalIF":4.7,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584021","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":"Possible changes in motor neuron discharge characteristics in presymptomatic amyotrophic lateral sclerosis","authors":"Maria Piotrkiewicz","doi":"10.1113/JP287788","DOIUrl":"10.1113/JP287788","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"602 24","pages":"6631-6635"},"PeriodicalIF":4.7,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584119","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":"Sphingosine-1-phosphate activates LRRC8 volume-regulated anion channels through Gβγ signalling.","authors":"Yulia Kostritskaia, Sumaira Pervaiz, Anna Klemmer, Malte Klüssendorf, Tobias Stauber","doi":"10.1113/JP286665","DOIUrl":"https://doi.org/10.1113/JP286665","url":null,"abstract":"<p><p>Volume-regulated anion channels (VRACs) formed by leucin-rich repeat containing 8 (LRRC8) proteins play a pivotal role in regulatory volume decrease by mediating the release of chloride and organic osmolytes. Apart from the regulation of cell volume, LRRC8/VRAC function underlies numerous physiological processes in vertebrate cells including membrane potential regulation, glutamate release and apoptosis. LRRC8/VRACs are also permeable to antibiotics and anti-cancer drugs, representing therefore important therapeutic targets. The activation mechanisms for LRRC8/VRACs are still unclear. Besides through osmotic cell swelling, LRRC8/VRACs can be activated by various stimuli under isovolumetric conditions. Sphingosine-1-phosphate (S1P), an important signalling lipid, which signals through a family of G protein-coupled receptors (GPCRs), has been reported to activate LRRC8/VRACs in several cell lines. Here, we measured inter-subunit Förster resonance energy transfer (FRET) and used whole-cell patch clamp electrophysiology to investigate S1P-induced LRRC8/VRAC activation. We systematically assessed the involvement of GPCRs and G protein-mediated signal transduction in channel activation. We found that S1P-induced channel activation is mediated by S1PR1 in HeLa cells. Following the downstream signalling pathway of S1PR1 and using toxin-mediated inhibition of the associated G proteins, we showed that Gβγ dimers rather than Gαi or Gαq play a critical role in S1P-induced VRAC activation. We could also show that S1P causes protein kinase D (PKD) phosphorylation, suggesting that Gβγ recruits phospholipase Cβ (PLCβ) with the consequent PKD activation by diacylglycerol. Notably, S1P did not activate LRRC8/VRAC in HEK293 cells, but overexpression of Gβγ-responsive PLCβ isoform could facilitate S1P-induced LRRC8/VRAC currents. We thus identified S1PR1-mediated Gβγ-PLCβ signalling as a key mechanism underlying isosmotic LRRC8/VRAC activation. KEY POINTS: Leucin-rich repeat containing 8 (LRRC8) anion/osmolyte channels are involved in multiple physiological processes where they can be activated as volume-regulated anion channels (VRACs) by osmotic cell swelling or isovolumetric stimuli such as sphingosine-1-phosphate (S1P). In the present study, using pharmacological modulation and gene-depleted cells in patch clamp recording and optical monitoring of LRRC8 activity, we find that LRRC8/VRAC activation by S1P is mediated by the G protein-coupled receptor S1PR1 coupled to G proteins of the Gi family. The signal transduction to LRRC8/VRAC activation specifically involves phospholipase Cβ activation by βγ subunits of pertussis toxin-insensitive heteromeric Gi proteins. S1P-mediated and hypotonicity-induced LRRC8/VRAC activation pathways converge in protein kinase D activation.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576630","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":"Dynamin independent mechanism of exo-endocytosis coupling.","authors":"Julia Bandura, Zhong-Ping Feng","doi":"10.1113/JP287403","DOIUrl":"https://doi.org/10.1113/JP287403","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576614","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":"Motor unit adaptation to disuse: crossing the threshold from firing rate suppression to neuromuscular junction transmission.","authors":"Mathew Piasecki","doi":"10.1113/JP284159","DOIUrl":"https://doi.org/10.1113/JP284159","url":null,"abstract":"<p><p>Neural conditioning to scenarios of muscle disuse is undoubtedly a cause of functional decrements that typically exceed losses of muscle size. Yet establishing the relative contribution of neural adaptation and the specific location in the motor pathway remains technically challenging. Several studies of healthy humans have targeted this system and have established that motor unit firing rate is suppressed following disuse, with a number of critical caveats. It is suppressed in the immobilized limb only, at relative and absolute force levels, and preferentially targets lower-threshold motor units. Concomitantly, electrophysiological investigation of neuromuscular junction transmission (NMJ) stability of lower-threshold motor units reveals minimal change following disuse. These findings contrast with numerous other methods, which show clear involvement of the NMJ but are unable to characterize the motor unit to which they belong. It is physiologically plausible that decrements observed following disuse are a result of suppressed firing rate of lower-threshold motor units and impairment of transmission of the NMJ of higher-threshold motor units. As such, motor units within the pool should be viewed in light of their varying susceptibility to disuse.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576620","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":"Oxyntomodulin physiology and its therapeutic development in obesity and associated complications.","authors":"Martin T W Kueh, Ming Chuen Chong, Alexander D Miras, Carel W le Roux","doi":"10.1113/JP287407","DOIUrl":"https://doi.org/10.1113/JP287407","url":null,"abstract":"<p><p>Incretins, such as glucagon-like peptide-1 (GLP1) and glucose-dependent insulinotropic polypeptide (GIP), have advanced the treatment landscape of obesity to a new pinnacle. As opposed to singular incretin effects, oxyntomodulin (OXM) activates glucagon receptors (GCGR) and glucagon-like peptide-1 receptors (GLP1R), demonstrating a more dynamic range of effects that are more likely to align with evolving 'health gains' goals in obesity care. Here, we will review the molecular insights from their inception to recent developments and challenges. This review will discuss the physiological actions of OXM, primarily appetite regulation, energy expenditure, and glucose homeostasis. Finally, we will shed light on the development of OXM-based therapies for obesity and associated complications, and outline important considerations for more translational efforts.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569857","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":"Post-stroke fatigue - a multidimensional problem or a cluster of disorders? A case for phenotyping post-stroke fatigue.","authors":"Annapoorna Kuppuswamy","doi":"10.1113/JP285900","DOIUrl":"https://doi.org/10.1113/JP285900","url":null,"abstract":"<p><p>Post-stroke fatigue is a chronic problem with significant impact on morbidity and mortality, which urgently needs effective treatments. The last decade has seen a considerable increase in interest in understanding the pathophysiology of fatigue and developing treatments. In this review, following a summary of theoretical frameworks to understand chronic fatigue, I make a case for why phenotyping fatigue is a necessary step to fully understand pathophysiology, which in turn is essential for the development of robust treatments. I then appraise current post-stroke fatigue literature with the view of identifying post-stroke fatigue phenotypes.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564981","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":"Experience-driven competition in neural reorganization after stroke.","authors":"Theresa A Jones, Victoria Nemchek, Michela Fracassi","doi":"10.1113/JP285565","DOIUrl":"https://doi.org/10.1113/JP285565","url":null,"abstract":"<p><p>Behavioural experiences interact with regenerative responses to shape patterns of neural reorganization after stroke. This review is focused on the competitive nature of these behavioural experience effects. Interactions between learning-related plasticity and regenerative reactions have been found to underlie the establishment of new compensatory behaviours and the efficacy of motor rehabilitative training in rodent stroke models. Learning in intact brains depends on competitive and cooperative mechanisms of synaptic plasticity. Synapses are added in response to learning and selectively maintained and strengthened via activity-dependent competition. Long-term memories for experiences that occur closely in time can be weakened or enhanced by competitive or cooperative interactions in the time-dependent process of stabilizing synaptic changes. Rodent stroke model findings suggest that compensatory reliance on the non-paretic hand after stroke can shape and stabilize synaptic reorganization patterns in both hemispheres, to compete with the capacity for experiences of the paretic side to do so. However, the competitive edge of the non-paretic side can be countered by overlapping experiences of the paretic hand, and might even be shifted in a cooperative direction with skilfully coordinated bimanual experience. Advances in the basic understanding of learning-related synaptic competition are helping to inform the basis of experience-dependent variations in stroke outcome.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142548579","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":"Biology, function and structure of the calcium homeostasis modulator family.","authors":"Rachel Polfer, Hiro Furukawa","doi":"10.1113/JP285197","DOIUrl":"https://doi.org/10.1113/JP285197","url":null,"abstract":"<p><p>Calcium homeostasis modulators (CALHMs) are the most recently discovered members of the large-pore channel family. They mediate the conductance of ions and larger molecules, such as ATP, and play critical roles in pathways related to Alzheimer's disease, neuroinflammation, neuromodulation, taste perception and innate immune responses. Since the inaugural report on CALHM1 in 2008, significant breakthroughs have revealed their biological roles, ion and ATP channel functions, and structures, positioning the field for further advancements. In this review, we discuss the overall progress and recent developments in understanding the biological roles, functions and molecular structures of CALHM proteins.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142523535","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":"Intermittent hypoxia and motor learning: new information and new questions.","authors":"Gino S Panza, Alexandra E Soltesz, Fei Zhao, Nora E Fritz, Andrew D Delgado, Tommy W Sutor","doi":"10.1113/JP287594","DOIUrl":"https://doi.org/10.1113/JP287594","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142523536","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}