JOURNAL OF PHYSIOLOGY-LONDON
JOURNAL OF PHYSIOLOGY-LONDON(英文缩写 J PHYSIOL-LONDON),ISSN 0022-3751,eISSN 1469-7793 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-09-28 至 2026-09-28，按本站收录文献的发表日期统计。
期刊介绍
历年影响因子趋势
| JCR 数据年份 | 影响因子 | JCR 分区 |
|---|---|---|
| 2021 | 6.228 | Q1 |
| 2022 | 5.500 | Q1 |
| 2023 | 4.700 | Q1 |
| 2024 | 4.400 | Q1 |
| 2025 | 4.600 | Q1 |
JOURNAL OF PHYSIOLOGY-LONDON 最新收录文献
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1. The first brain at the centre: An enteric reframing of the nervous system.
PMID:DOI:日期:2026-09-25该文献暂无摘要。
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2. Macroscopic to ultrastructural analyses identify the loss of myofibrils as the primary mediator of ageing- and disuse-induced muscle fibre atrophy.
PMID:DOI:日期:2026-09-25Ageing and disuse are two of the most clinically relevant conditions associated with the loss of skeletal muscle mass, yet the ultrastructural adaptations that drive these losses remain poorly defined. Indeed, even the most basic questions, such as whether radial atrophy of muscle fibres is driven primarily by reductions in myofibril size, and/or the loss of myofibrils, remain unanswered. To address this gap, skeletal muscle structure was assessed at the macroscopic, microscopic and ultrastructural levels in young and older humans and mice. In humans, magnetic resonance imaging was used to measure quadriceps muscle volume and cross-sectional area (CSA), whereas vastus lateralis biopsies underwent standard immunohistochemistry for microscopic evaluations, coupled with a next-generation fluorescence imaging pipeline for ultrastructural analyses. Parallel experiments were conducted in mice, including a unilateral immobilization model of disuse-induced atrophy. Ageing in humans was associated with lower muscle volume and CSA, along with radial atrophy of SERCA1-positive fibres, whereas SERCA2-positive fibre CSA was preserved. Notably, the radial atrophy of SERCA1 fibres was largely explained by a lower number of myofibrils, rather than a smaller size of the myofibrils. Similar alterations were observed in aged mice, although SERCA1 fibres also exhibited slightly smaller myofibril size. In mice, disuse likewise caused radial muscle fibre atrophy that was again almost exclusively associated with a lower number of myofibrils. Collectively, these findings identify the loss of myofibrils as a central and conserved mechanism that mediates radial muscle fibre atrophy during ageing and disuse, highlighting a potential therapeutic target for preserving skeletal muscle mass. KEY POINTS: Skeletal muscles atrophy with ageing and disuse, and the loss of muscle mass increases the risk of falls, disability and all-cause mortality. Skeletal muscles are composed of long cells called muscle fibres, and each fibre is densely packed with thread-like structures called myofibrils; however, whether muscle fibre atrophy is primarily driven by reductions in the size of the myofibrils, and/or the loss of myofibrils, is not known. Using a next-generation imaging pipeline, this study examined muscle samples from young and older adults, as well as from young and old mice. The results show that muscle fibre atrophy during both ageing and disuse is mainly associated with a lower number of myofibrils, rather than a smaller size of the myofibrils. Identifying the loss of myofibrils as the primary mechanism underlying muscle fibre atrophy highlights a specific therapeutic target for preserving muscle as people age or recover from injury.
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3. Architecture of the cardiac transverse-axial tubular system across different mammalian species.
PMID:DOI:日期:2026-09-24Cardiac excitation-contraction coupling relies on a pancellular network of regular cardiomyocyte surface membrane invaginations, termed the transverse-axial tubular system (TATS). The TATS is ubiquitously present in adult mammalian cardiomyocytes, enabling efficient structural and functional coupling of sarcolemma and intracellular Ca stores. However TATS ultrastructural characteristics across species, and their relation to cardiomyocyte morphology and physiological parameters such as heart rate, remain largely unexplored. Here we quantified TATS and cardiomyocyte features in a confocal microscopy dataset (91 three-dimensional image volumes) obtained from tissue slices across eight species (mouse, rat, rabbit, pig, horse, elephant, whale, and humans). We applied a semi-automated image analysis pipeline to quantify mean cytosolic distances to the nearest TATS element (Cyto-TATS), transverse tubule fraction, and cardiomyocyte dimensions. Cyto-TATS and transverse tubule fraction differed substantially between species, with the lowest Cyto-TATS in mouse and highest in humans. No significant within-species associations between Cyto-TATS and cardiomyocyte size were detected in six of eight species. Associations were limited to pig (cross-sectional area and width) and elephant (area, depth, and width), although elephant was represented by a single subject. Across all species, Cyto-TATS positively correlated with species' lifespan and body mass, and was inversely correlated with resting heart rate. Our findings reveal structural scaling principles in cardiac cellular ultrastructure and provide a resource for studying TATS organisation in health and disease. As TATS remodelling is a common hallmark of cardiac pathology, awareness of species differences in reference states and remodelling dynamics is needed to guide the design and interpretation of translational research. KEY POINTS: The transverse-axial tubular system (TATS) is essential for efficient excitation-contraction coupling in cardiomyocytes and, consequently, normal cardiac function. However systematic comparisons of TATS architecture across mammalian species remain limited. We analysed 91 three-dimensional (3D) image volumes, obtained using confocal microscopy, from eight mammalian species (mouse, rat, rabbit, pig, horse, humans, elephant, whale) using a unified image analysis pipeline. We quantified mean cytosolic distance to the nearest TATS element (Cyto-TATS), transverse tubule percentage, and 3D cardiomyocyte morphology. Cyto-TATS and transverse tubule percentage showed species-dependent patterns, with Cyto-TATS being lowest in mouse and highest in human. Across species, Cyto-TATS covaries with organismal physiology (lifespan, body mass, and resting heart rate). Our quantitative data provide a cross-species reference framework for interpreting physiological adaptations and pathological remodelling of the cardiac TATS.
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4. Mitochondrial permeability transition in skeletal muscle phenocopies muscle alterations seen in cancer cachexia and other wasting conditions.
PMID:DOI:日期:2026-09-24Skeletal muscle in wasting conditions often exhibits atrophy, mitochondrial respiratory dysfunction and fragmentation of the acetylcholine receptor (AChR) cluster at the endplate. The accompanying alterations in mitochondrial morphology suggest that mitochondria may be involved in muscle pathology in these conditions. To address this gap, we tested an established pathological mechanism in ischaemia-reperfusion injury and neurodegeneration but poorly studied in skeletal muscle: mitochondrial permeability transition (mPT). We tested if mPT recapitulated phenotypes common in wasting conditions, whether tumour-conditioned media (TCM) could promote mPT and compared differentially expressed genes (DEGs) induced by mPT with DEGs observed in a mouse model of pancreatic cancer cachexia. Inducing mPT in mouse skeletal muscle bundles progressively altered mitochondrial cristae morphology, culminating in a breach of the outer mitochondrial membrane. Inducing mPT in mouse muscle fibres increased mitochondrial reactive oxygen species (mROS) and caspase 3 activity and caused atrophy. Inducing mPT caused a complex I mitochondrial respiratory impairment, increased lysosome-mitochondrion colocalization and fragmented the AChR cluster at the muscle endplate. The Ca threshold for mPT, mitochondrial calcein colocalization and mitochondrial membrane potential were reduced by TCM in skeletal muscle or C2C12 myoblasts, respectively. Knockout of the mPT-regulating protein CypD attenuated the reduction in Ca threshold for mPT by TCM. Inhibitors of mPT attenuated atrophy with TCM in C2C12 and human primary myotubes. Finally, there was overlap between the DEGs of mPT and diaphragm muscle in a mouse model of pancreatic cancer cachexia during the muscle-wasting phase. We conclude that mPT should be explored as a therapeutic target in muscle-wasting disorders. KEY POINTS: Mitochondrial permeability transition (mPT) induces marked alterations in mitochondrial morphology and muscle phenotypes that are common in wasting conditions. mPT is promoted by tumour-derived factors in a manner that depends in part on the mPT-regulating protein CypD. mPT generates transcriptional alterations that overlap with cachectic muscle in a mouse model of pancreatic cancer, particularly during the period of muscle wasting. Pharmacological targeting of mPT attenuates or prevents atrophy in C2C12 and human primary myotubes, respectively.
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5. A structure-based model that describes activation and inactivation of a sodium channel.
PMID:DOI:日期:2026-09-24While the Hodgkin-Huxley formalism successfully describes sodium channel gating, the molecular origin of its nonlinear voltage dependence remains unclear. We developed a structure-based model of Na1.4 representing the four voltage-sensing domains, the isoleucine-phenylalanine-methionine (IFM) motif and the S6 gate as interacting binary variables, with activation parameters constrained by domain-specific fluorescence measurements. The fitted model reveals strongly heterogeneous voltage sensors whose interactions produce cooperative activation, suppressing channel opening at subthreshold voltages. Using timescale separation, we coarse-grain the 64-microstate system to obtain the Hodgkin-Huxley-like factorization P = m × h, where represents cooperative activation and represents availability. The reduced theory shows that the voltage dependence of is inherited from the domain-IV voltage sensor. Because domain IV activates at more hyperpolarized voltages than the collective activation of domains I-III required for opening, availability declines before the channel reaches its main activation range. Coupling of domain IV to IFM engagement and S6 gate closure further controls the magnitude of this shift. Thus, the model identifies the molecular origin of the separation between activation and availability curves. KEY POINTS: Sodium channels are proteins in nerve and muscle cells that open briefly to trigger electrical signals, then close. The 1952 Hodgkin-Huxley model captures this behaviour by treating the channel's four voltage sensors as independent. However, experiments show the sensors are not independent: moving one changes how the others respond to voltage. We built a structure-based mathematical model of the muscle sodium channel in which all four sensors and the inactivation gate interact and fitted it to measurements of each sensor's movement. The model reproduces classic channel behaviour but shows it arises from strong cooperation between sensors and explains why the channel stops being able to open at more negative voltages than those that open it - an effect traced to a single sensor. This voltage gap helps set the range over which muscle sodium channels carry current. Analogous shifts in related sodium-channel isoforms also underlie inherited heart-rhythm disorders, linking structure to disease.
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6. {"_":"Resolution and automated analysis of single-cell Ca waves within living myocardial tissue slices.","sup":["2+"]}
PMID:DOI:日期:2026-09-24Current approaches for the study of arrhythmogenic Ca waves in intact cardiac tissue have limited capacity to study the relationship between single-cell properties and the tissue environment. Particularly, wide-field Ca imaging captures large areas but merges signals from multiple cells, while confocal imaging provides (sub)cellular resolution but is limited to a small number of cells. The aim of this study was to develop an imaging and analysis pipeline capable of extracting single-cell Ca wave dynamics across large fields within the intact multicellular tissue. Living myocardial slices were prepared from left ventricular tissue from pig and human hearts. Ca transients and waves reported by Fluo8 were imaged in regions of 20-100 cells at the slice surface. Following a 2 min conditioning period of 2 Hz pacing under adrenergic stimulation, Ca waves were evident during the rest period. Images were recorded at 200 fps. After image processing, single Ca waves were identified and propagation paths were tracked using TrackMate. From these tracks, Ca wave parameters (number of tracks, coordinates and kinetics) were extracted for quantitative analysis and assigned to individual cardiomyocytes using a maximum fluorescence intensity mask to identify cellular borders. In healthy pig cardiac tissue, we captured and quantified single-cell Ca wave dynamics, detecting variability within the population and an absence of synchronization. The recording of Ca dynamics across a large cell population and their cell-cell interactions bridges the gap between cell- and tissue-level observations. Future studies of diseased tissue will offer new insights into mechanisms driving aberrant cellular Ca activity and the translation into arrhythmias. KEY POINTS: We developed an approach that allows high frame-rate imaging of living cardiac tissue, while retaining capacity to identify Ca waves in single cells. In myocardial slice preparations from pig and human hearts, we recorded Ca waves and, using image analysis tools, tracked their paths and properties simultaneously within individual cells and across a large cell population (20-100 cells) within a region of interest. This approach bridges a key gap between single-cell observations and whole-tissue behaviour, and can offer deeper insights into how cellular Ca waves could expand and propagate in the heart. Our approach provides a new methodology to study cellular mechanisms that lead to arrhythmias in diseased cardiac tissue.
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7. A peak at the leak: Background conductances as efficient controllers of autonomous pacemaking.
PMID:DOI:日期:2026-09-23该文献暂无摘要。
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8. The influence of force on the encoding and perception of affective touch.
PMID:DOI:日期:2026-09-23Stroking touch has been shown to be most pleasant at intermediate velocities of 1-10 cm s, which relates well to the activity of C-low-threshold mechanoreceptors (C-LTMRs), also called C-tactile afferents in humans, that have been implicated in encoding positive affective touch. This well-established finding has been demonstrated at gentle stroking forces (typically, 0.4 N peak normal force), yet few studies have investigated the effect of force on the perception of stroking touch or on the activity of C-LTMRs. We investigated the pleasantness and intensity of stroking touch (0.3, 1, 3, 10 and 30 cm s) at different forces (0.2, 0.4, 0.8, 1.2, 1.6 and 2.0 N) on hairy forearm skin and compared this with responses from C-LTMRs during stroking touch at the same velocities, but over fewer forces (0.05, 0.4 and 1.5 N). We found significant effects of stroking velocity and force for both tactile pleasantness and intensity ratings. Pleasantness showed the typical inverted U-shaped relationship over stroking velocities, but this was modified by force; higher forces significantly decreased pleasantness at faster velocities. Conversely, tactile intensity increased linearly with both increasing velocity and force. Recordings from seven C-LTMRs showed that their firing frequency changed with stroking velocity, but that they were strongly modulated by force. Overall, we demonstrate the profound effect that force has on the perception of stroking touch, whereby tactile pleasantness and intensity appear to be a multi-faceted construct that is related to C-LTMR and Aβ-LTMR activity, respectively, but that the firing in individual mechanoreceptor populations cannot account fully for percepts. KEY POINTS: The skin is highly sensitive to small mechanical deformations, including dynamic touch and different forces. We obtained perceptual ratings for touch pleasantness and intensity over different stroking velocities and forces applied to the forearm. This was also compared with microneurography recordings from C-low-threshold mechanoreceptors (C-LTMRs). Building on previous work, we find that it is not only stroking velocity that affects pleasantness and intensity perception, but also stroking force. Pleasantness ratings decreased more at higher forces when the stroking was faster. C-LTMR firing showed that differences in force were readily encoded, although the same force-velocity interaction was not seen. This work expands the literature on affective touch to encompass the effects of force, which clearly modulates pleasantness. C-LTMR force and velocity information is likely to combine with information from all types of mechanoreceptors, including those from the fascia, to produce the resulting percept.
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10. Medullary raphe and the retrotrapezoid nucleus: New insights into central respiratory chemoreception.
PMID:DOI:日期:2026-09-21该文献暂无摘要。