Acta Physiologica最新文献

{"title":"Concept Cells and the Neural Bases of Human Memory.","authors":"Beatriz S Arruda, Rodrigo Quian Quiroga","doi":"10.1111/apha.70234","DOIUrl":"10.1111/apha.70234","url":null,"abstract":"<p><p>Single-neuron recordings from the medial temporal lobe of patients undergoing epilepsy surgery have revealed \"concept cells\" that respond selectively and invariantly to meaningful stimuli such as specific people, places, or objects. These responses offer a unique window into how individual neurons encode high-level, multimodal representations-the building blocks of episodic memory-that differ from the more distributed, often hierarchical representations supporting semantic memory in the neocortex. Episodic and semantic memory, the systems for storing past experiences and conceptual knowledge, have traditionally been regarded as distinct. However, converging evidence from neuroimaging, lesion studies, and electrophysiological recordings challenges this strict dichotomy. This review synthesizes findings from human single-neuron recordings to re-examine the traditional distinction between episodic and semantic memory. We propose that the primary difference between the two systems lies in the structure of the associations they support: sparse, arbitrary links supporting episodic memory in the hippocampus versus ordered, hierarchical representations supporting semantic memory in the neocortex.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 6","pages":"e70234"},"PeriodicalIF":5.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13184804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147968881","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":"Mechanism of Fluid Reabsorption in Kidney Proximal Tubule: Interplay Between Lateral Na⁺/K⁺-ATPase and AQP1 and SGLT1 Mediated Water Fluxes.","authors":"Erik Hviid Larsen, Jens Nørkær Sørensen","doi":"10.1111/apha.70242","DOIUrl":"10.1111/apha.70242","url":null,"abstract":"<p><strong>Aims: </strong>The mechanism of isosmotic water reabsorption in the kidney proximal tubule, with a focus on the interaction between the lateral Na⁺/K⁺-ATPase, apical water pathways mediated by AQP1 and SGLT1, and paracellular water flow through Claudin-2.</p><p><strong>Methods: </strong>A mathematical model of proximal tubular transport was used to compute coupled ion, solute, and water fluxes. The model included apical ENaC and a full electrogenic Na⁺/K⁺-ATPase formulation that incorporated its electromotive force, E^pump, as a thermodynamic constraint linked to ATP hydrolysis at the pump site.</p><p><strong>Results: </strong>Published cellular cation concentrations indicate metabolic stress in excised tubules, providing biophysical rationale for interpreting enhanced NHE3 activity and proton secretion in isolated proximal tubules as consequences of reduced ΔG^ATP, while modeling apical Na⁺ entry under non-stressed conditions by ENaC. Active Na⁺ transport generated a slightly hyperosmotic and hyperbaric lateral intercellular space, driving fluid efflux across the interspace basement membrane. Without ion recirculation, the absorbed fluid remained hyperosmotic. Isosmotic reabsorption therefore required ion recirculation between serosal fluid and the lateral intercellular space. SGLT1-mediated glucose uptake redistributed water flow between AQP1, SGLT1 and the paracellular pathway, whereas total water reabsorption remained closely linked to active Na⁺ transport, consistent with experiments.</p><p><strong>Conclusion: </strong>Proximal tubular water reabsorption is not explained by passive osmotic equilibration alone, but emerges from thermodynamic coupling between active Na⁺ transport, water permeability pathways, and regulated ion recirculation. The proximal tubule therefore functions as an ATP-consuming epithelial fluid pump that maintains isosmotic reabsorption by using additional metabolic energy to convert initially hyperosmotic absorbate into isosmotic reabsorbed fluid.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 6","pages":"e70242"},"PeriodicalIF":5.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13184667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147968866","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":"Addressing Key Limitations of Diastolic Function Assessment in Mouse Echocardiography by Enabling Robust Retrospective Analysis From a Standard Imaging View.","authors":"Michael Marterstock, Antje Schauer, Alina Maslakova, Annett Opitz, Peter Dieterich, Stephan Speier, Susanne Kämmerer, Peter Mirtschink, Irakli Kopaliani, Andreas Deussen","doi":"10.1111/apha.70250","DOIUrl":"10.1111/apha.70250","url":null,"abstract":"<p><strong>Aim: </strong>Echocardiographic assessment of diastolic function in mice remains challenging because parameters translated from clinical practice are constrained by murine physiology. In particular, parameters derived from early (E) and late (A) transmitral filling velocities are frequently compromised by wave fusion at higher heart rates. Here, we quantified these limitations and evaluated an alternative method for measuring isovolumetric relaxation time (IVRT), a marker reflecting ventricular relaxation and a key element of established algorithms specific for murine diastolic function assessment.</p><p><strong>Methods: </strong>In a non-A4C-view-dependent echocardiographic measurement (NAEM) approach, speckle-tracking analysis of standard brightness-mode (B-mode) cine loops from the parasternal long-axis view (PSLAX) enabled E/A ratio and IVRT assessment. Mice with unimpaired heart function, heart failure with preserved ejection fraction (HFpEF), or heart failure with reduced ejection fraction (HFrEF) (n = 8 each) underwent standard Doppler-based and NAEM-based measurement of E/A ratio and IVRT.</p><p><strong>Results: </strong>In mice with unimpaired heart function and HFpEF, heart rate-dependent E and A wave fusion occurred at an estimated threshold of approximately 460 bpm, whereas advanced HFrEF led to frequent fusion independent of heart rate. NAEM-derived IVRT showed strong agreement with the Doppler reference (r² = 0.9339, p < 0.0001), minimal bias (-1.4 ms), and similar inter-observer variability. In contrast, NAEM-derived E/A ratio did not show adequate performance.</p><p><strong>Conclusion: </strong>These findings further support the shift toward specific algorithms for diastolic function assessment in murine echocardiography. The validated NAEM approach supports application of such protocols without dedicated Doppler recordings by using PSLAX B-mode cine loops, thereby lowering technical barriers for future studies and enabling robust retrospective analysis of existing datasets.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 6","pages":"e70250"},"PeriodicalIF":5.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13176516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147939462","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":"Fentanyl Compromises Lower-Airway Mechanics and Naloxone Triggers a Transient Mechanical Overshoot.","authors":"Riley R Parks, Marissa J Andersen, Mackenna L Hatfield, Madeline M Johnson, Nicholas J Burgraff","doi":"10.1111/apha.70253","DOIUrl":"10.1111/apha.70253","url":null,"abstract":"<p><strong>Aim: </strong>Opioid-induced respiratory depression (OIRD) is the leading cause of death following opioid overdose, due to its effects on central rhythm generation, and airway and thoracic constriction. While the effects on rhythm generation have been well documented, the effects of fentanyl on airway constriction are less well understood. We tested the hypothesis that the lower airways uniquely contribute to fentanyl-induced airway constriction and may provide a potential additional therapeutic target for overdose reversal.</p><p><strong>Methods: </strong>Urethane-anesthetized mice were mechanically ventilated while pressure and airflow signals were recorded in vivo before and following intraperitoneal injection of fentanyl (500 μg/kg). The effects of naloxone, salbutamol, atropine, and positive-end expiratory pressure (PEEP) were evaluated to determine the extent of lower airway contributions to airflow obstruction during overdose.</p><p><strong>Results: </strong>In addition to fentanyl's known depressive effects on respiratory drive, the introduction of fentanyl further disrupted airway patency by increasing dynamic resistance and decreasing lung compliance. These effects on respiration were not observed with naloxone alone and were reversed through administration of salbutamol, atropine, or introduction of PEEP. Importantly, opioid reversal with naloxone also produced a transient overshoot in dynamic resistance and lung compliance immediately following administration. We also observed an increase in physiological sighing following opioid removal.</p><p><strong>Conclusions: </strong>The lower airways contribute to fentanyl-induced airway constriction and serve as a potential additional therapeutic target following overdose. Fast-acting pharmacological agents may be used in tandem with naloxone to reduce changes in dynamic resistance and lung compliance produced by fentanyl while also limiting any adverse effects of naloxone itself.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 6","pages":"e70253"},"PeriodicalIF":5.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147968888","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":"Frogs Uncouple Neural Activity From Oxygen Consumption After Hibernation.","authors":"Hafsa Yaseen, Joseph M Santin","doi":"10.1111/apha.70247","DOIUrl":"10.1111/apha.70247","url":null,"abstract":"<p><strong>Aim: </strong>Aerobic metabolism supplies ~90% of the ATP for neural activity. In frogs, activity has large aerobic needs typical of an average vertebrate, but surprisingly, can shift to using only glycolysis upon emergence from hibernation. We hypothesized that hibernation triggers a global reduction in the aerobic cost of neural function.</p><p><strong>Methods: </strong>We simultaneously measured activity of the brainstem respiratory network via motor nerves and tissue O₂ partial pressure (pO₂) in vitro from control and hibernated bullfrogs (4 weeks cold submergence; 4°C). To identify which functions differentially consume O₂, we sequentially blocked activity and various cellular processes requiring activity-independent ion regulation and used the resulting tissue pO₂ change (ΔpO₂) as an index of O₂ consumed. We further assessed how activity varies as a function of tissue pO₂ and how O₂ consumption varies across network activity levels.</p><p><strong>Results: </strong>Despite similar network activity levels, we provide three lines of evidence that hibernation reduces its aerobic requirement. First, hibernators consume less O₂ for baseline activity. Second, network output remains stable from baseline to anoxia, whereas moderate hypoxia disrupts controls. Finally, accelerating activity does not enhance O₂ consumption as in controls, but aerobic metabolism ultimately increases during seizure-like activity.</p><p><strong>Conclusion: </strong>Hibernating frogs reduce aerobic needs for sustaining physiological levels of neural activity, revealing how they overcome the challenge of restarting motor circuits on the background of hypoxia during emergence from hibernation. More broadly, vertebrate neural circuits seemingly constrained by aerobic metabolism can exhibit substantial plasticity in the aerobic requirements for function.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 6","pages":"e70247"},"PeriodicalIF":5.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13193244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147979699","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":"Diabetes Is a Hyperdynamic Circulatory Disease.","authors":"Emma H J Malm, Rakin Hadad, Walid Warrad, Ali Asmar, Philip Lykkebæk Bonde, Helena Domínguez, Ahmad Sajadieh, Steen B Haugaard","doi":"10.1111/apha.70249","DOIUrl":"10.1111/apha.70249","url":null,"abstract":"<p><strong>Aim: </strong>A hyperdynamic circulation in type 2 diabetes (T2D) has been proposed. We investigated this hypothesis in patients admitted to a tertiary care hospital in Denmark.</p><p><strong>Methods: </strong>Cardiac index (CI) and systemic vascular resistance (SVR) were estimated noninvasively in 933 patients admitted to the medical division of the emergency department (ED) of Bispebjerg University Hospital, Copenhagen, Denmark, between May 2019 and January 2023. The population included 154 people with T2D.</p><p><strong>Results: </strong>Among people with T2D, CI was 17% higher (p < 0.0001) and SVR was 24% lower (p < 0.0001) compared to people without T2D. In linear regression models adjusted for age, sex, smoking status, body mass index, comorbidities, and medication for hypertension, T2D was independently associated with increased CI and decreased SVR (p < 0.001). This association remained significant after propensity matching on age, sex, BMI, hypertension, ischemic heart disease, and congestive heart failure. People with T2D treated with insulin (n = 43) exhibited higher CI (p = 0.04) and lower SVR (p = 0.003) than non-insulin-treated people with T2D (n = 111).</p><p><strong>Conclusions: </strong>Our findings support the notion that hyperdynamic circulation is an intrinsic feature of T2D, but further studies should explore its relevance for prognosis, risk stratification, and targeted interventions.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 6","pages":"e70249"},"PeriodicalIF":5.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147947309","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":"T Cell Dysfunction in the Acidic Tumor Microenvironment.","authors":"F B Christiansen, E S Novella, A V Lindemann, J F H Cordes, S F Pedersen","doi":"10.1111/apha.70260","DOIUrl":"10.1111/apha.70260","url":null,"abstract":"<p><p>Solid tumors are characterized by profound metabolic and vascular abnormalities that generate a hostile tumor microenvironment (TME) marked by extracellular acidosis, hypoxia, and nutrient deprivation. While the consequences of these conditions for cancer cell behavior have been extensively studied, their impact on anti-tumor immune responses-particularly T cell function-has only recently gained attention. In this review, we summarize and critically discuss current knowledge on how acidic TME conditions affect the cytotoxic CD8+ T cells which are essential for anti-tumor immunity, and the protumorigenic, regulatory T cells (Tregs). An emerging body of literature shows that TME acidosis restricts cytotoxic CD8+ T cell motility and tumor penetration, suppresses cytokine production and secretion despite preserved transcription, impairs proliferation, and reduces cytotoxic killing capacity. These effects are closely linked to acid-induced metabolic reprogramming, including inhibition of glycolysis, altered mTOR and MYC signaling, and a shift toward fatty acid-dependent oxidative metabolism. In contrast, Tregs, which are metabolically adapted to rely on oxidative phosphorylation and lactate utilization, are comparatively resilient to acidic stress, and acidosis can enhance their suppressive capacity, thereby further skewing the immune balance toward tolerance. We highlight emerging evidence that tumor acidosis modulates immune checkpoint pathways, including pH-sensitive signaling through VISTA and regulation of PD-L1 expression, with important implications for immunotherapy sensitivity. We posit that limiting tumor acidosis may enable restoration of anti-tumor T cell function and improve therapeutic response to immune checkpoint blockade and adoptive T cell therapies.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 6","pages":"e70260"},"PeriodicalIF":5.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147985745","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":"Autoantibodies in Patients With Arrhythmogenic Cardiomyopathy Activate GSK-3β, Resulting in a Loss of Cardiomyocyte Cohesion","authors":"Soumyata Pathak,&nbsp;Konstanze Stangner,&nbsp;Ellen Kempf,&nbsp;Sina Moztarzadeh,&nbsp;Matthias Hiermaier,&nbsp;Stephanie Wider,&nbsp;Marlene Rauschmayer,&nbsp;Tatjana Williams,&nbsp;Andreas Stengl,&nbsp;Brenda Gerull,&nbsp;Ruth Biller,&nbsp;Sebastian Clauss,&nbsp;Stefan Kääb,&nbsp;Tomo Šarić,&nbsp;Sunil Yeruva,&nbsp;Jens Waschke","doi":"10.1111/apha.70254","DOIUrl":"10.1111/apha.70254","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiac desmosome disease, as more than 50% of affected patients carry pathogenic variants in desmosome protein-coding genes. In this study, we focused on the role and mechanisms of pathogenic and non-pathogenic autoantibodies against intercalated disc (ICD) proteins such as desmoglein2 (DSG2) in ACM patients, healthy relatives (HR), and murine ACM models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>IgG fractions from ACM patients, HR, healthy controls, and murine ACM models were isolated. Besides ELISA and cleavage assay, dissociation assay, immunostaining, Triton-X-100 assay, Western blots, and atomic force microscopy were performed in murine cardiac slices, HL-1 cells, or induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>IgG fractions from ACM patients and HR, but not murine ACM model-derived or grouped healthy controls IgG (G-HC), revealed positive ICD staining. Three out of six ACM patients derived IgGs that reduced cardiomyocyte cohesion. Pathogenic autoantibodies, bound to DSG2 in healthy and ACM hiPSC-CMs, cleaved and reduced DSG2 interaction at the molecular level. We investigated GSK-3β contribution to the cardiomyocyte cohesion loss and observed GSK-3β reduced baseline cohesion in cultured cardiomyocytes and cardiac slices. Among five ACM-IgGs, three HR-IgGs tested, three pathogenic ACM-IgGs activated GSK-3β upstream of p38MAPK, leading to phosphorylation and junctional loss of β-catenin. GSK-3β inhibition rescued the loss of cell cohesion in ACM hiPSC-CMs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Pathogenic autoantibodies targeting DSG2 are present in ACM patients and impair cardiomyocyte cohesion in a GSK-3β-dependent manner. In contrast, autoantibodies are absent in murine ACM models and are non-pathogenic in some patients and HR.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 7","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70254","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148136100","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 7","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148090042","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 7","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148090043","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}