Acta Physiologica最新文献

{"title":"Uteroplacental microvascular remodeling in health and disease","authors":"Ruizhi Li,&nbsp;Lei Ma,&nbsp;Yingchun Geng,&nbsp;Xiaoxue Chen,&nbsp;Jiaxi Zhu,&nbsp;Hai Zhu,&nbsp;Dong Wang","doi":"10.1111/apha.70035","DOIUrl":"https://doi.org/10.1111/apha.70035","url":null,"abstract":"<p>The microvascular system is essential for delivering oxygen and nutrients to tissues while removing metabolic waste. During pregnancy, the uteroplacental microvascular system undergoes extensive remodeling to meet the increased demands of the fetus. Key adaptations include vessel dilation and increases in vascular volume, density, and permeability, all of which ensure adequate placental perfusion while maintaining stable maternal blood pressure. Structural and functional abnormalities in the uteroplacental microvasculature are associated with various gestational complications, posing both immediate and long-term risks to the health of both mother and infant. In this review, we describe the changes in uteroplacental microvessels during pregnancy, discuss the pathogenic mechanisms underlying diseases such as preeclampsia, fetal growth restriction, and gestational diabetes, and summarize current clinical and research approaches for monitoring microvascular health. We also provide an update on research models for gestational microvascular complications and explore solutions to several unresolved challenges. With advancements in research techniques, we anticipate significant progress in understanding and managing these diseases, ultimately leading to new therapeutic strategies to improve maternal and fetal health.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726945","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":"Epithelial membrane transport and kidney physiology","authors":"Henrik Dimke","doi":"10.1111/apha.70038","DOIUrl":"https://doi.org/10.1111/apha.70038","url":null,"abstract":"&lt;p&gt;Epithelial membrane transport is fundamental to uphold many physiological processes in the kidney and beyond. Since its founding as &lt;i&gt;Skandinavisches Archiv für Physiologie&lt;/i&gt; in 1889, &lt;i&gt;Acta Physiologica&lt;/i&gt; has published many groundbreaking studies in this field.&lt;span&gt;&lt;sup&gt;1, 2&lt;/sup&gt;&lt;/span&gt; These include August Krogh's discoveries on ion absorption in frog skin and the development of the Ussing chamber system. To honor these and many other contributions, a special series on &lt;i&gt;membrane proteins, epithelial transport, and kidney physiology&lt;/i&gt; was launched in &lt;i&gt;Acta Physiologica&lt;/i&gt; in 2023.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Now, some two years later, the series is drawing to a close, with only a few manuscripts still under review.&lt;/p&gt;&lt;p&gt;The &lt;i&gt;Acta Physiologica&lt;/i&gt; special series has featured both original research articles and full-length reviews, covering recent advances in epithelial transport throughout the various bodily organs, as well as physiological and pathophysiological mechanisms in the kidney. The most recent contributions in this series are highlighted here, and all contributions are now being assembled in a virtual issue.&lt;/p&gt;&lt;p&gt;A central theme of this series is the molecular machinery that drives epithelial transport and its regulation. With respect to the role of tight junctions and paracellular transport, Pouyiourou et al.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; investigated ion permeability profiles of renal paracellular channel-forming claudins. This original study characterized the tight junction proteins in a cell model with minimal endogenous claudin expression.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; Their findings offer key insights into how claudins determine tubular ion permeability along the different segments of the nephron, and thus advance our understanding of selective ion transport in the kidney.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;The impact of loop diuretics on renal calcium and magnesium handling is also reviewed. Loop diuretics disrupt the driving force required for paracellular transport in the tubular epithelium, thereby reducing mineral reclamation by the kidney.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; In contrast, thiazide diuretics, which are frequently used to reduce blood pressure, limit urinary calcium excretion, and are therefore used to treat kidney stone disease. In this special series, Bargagli et al review the use of thiazides for kidney stone prevention and examine off-target effects on, for example, glucose tolerance.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; Another hormone relevant to mineral balance is the anti-aging hormone klotho. For the special series, Grigore et al.&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt; comprehensively review the physiology of klotho-deficient mouse models and provide insights into the role of klotho in the regulation of renal electrolyte transport and mineral balance.&lt;/p&gt;&lt;p&gt;An original study by Lasaad et al.&lt;span&gt;&lt;sup&gt;8&lt;/sup&gt;&lt;/span&gt; explores the role of growth differentiation factor 15 (GDF15) in regulating renal collecting duct cell plasticity in r","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707632","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":"Host-microbiome homeostasis: Unveiling the complex interactions shaping health and disease","authors":"Pontus B. Persson","doi":"10.1111/apha.70034","DOIUrl":"https://doi.org/10.1111/apha.70034","url":null,"abstract":"&lt;p&gt;The relationship between the human body and its microbial communities is becoming increasingly recognized as essential to our overall health. What we once thought of as a mere collection of bacteria, fungi, and other microorganisms now turns out to play a far more active role in maintaining our health or contributing to disease. This connection, known as host-microbiome homeostasis, refers to the balance between our bodies and the microbes residing within us. When this balance is disrupted, it can lead to conditions such as obesity, asthma, epilepsy, and even heart disease. Recent studies in this field shed light on the nature of this coexistence and pave the way toward therapies that harness the power of the microbiome to treat a variety of health issues.&lt;/p&gt;&lt;p&gt;This special series builds on Acta Physiologica's strong standing in the field&lt;span&gt;&lt;sup&gt;1-3&lt;/sup&gt;&lt;/span&gt; and comprises studies delving into different aspects of microbiome research. From using engineered bacteria to fight metabolic diseases to exploring the role of diet and early-life microbial exposure in asthma, these studies highlight just how interconnected our health is with the microbes living in and on us.&lt;/p&gt;&lt;p&gt;One of the studies, led by Ciocan and Elinav,&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; explores the idea of using genetically engineered bacteria to change the gut microbiome in ways that can treat disorders like obesity and diabetes. It is a fascinating step toward developing new treatments that could shift the balance of the microbiome for better health. A further article highlights the gut-lung axis and how early-life microbiota might influence asthma. Early-life exposures to microbes may play a major role in determining whether a child is more likely to develop asthma. Factors like how babies are born, whether they are breastfed, and their early diets all influence the development of their gut microbiome, which in turn affects immune responses. This could mean that by targeting the microbiome early on, there may be new opportunities to prevent asthma before it even begins. Pirr and colleagues explore the neonate respiratory microbiome.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; For a long time, we assumed that the respiratory tract was relatively sterile; yet, like the gut, it is home to a variety of microbes. The study reveals how the respiratory microbiome develops in newborns and how factors like delivery method, diet, and early infections can shape the microbial communities in the lungs. Understanding how these microbial communities interact with the immune system could lead to new ways to prevent respiratory diseases in children.&lt;/p&gt;&lt;p&gt;Diet is another area where the microbiome shows its influence, as outlined by Schoeler and his team.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; We know that drastic changes in diet can dramatically alter the gut microbiome. This study explores the more subtle effects of typical, everyday dietary variations. By observing how small shifts in diet influence the gut microbiota in both","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 4","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689403","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":"Lack of renal NHE1 exacerbates lithium-induced nephrogenic diabetes insipidus","authors":"Gabriella Blanco,&nbsp;Jianxiang Xue,&nbsp;Linto Thomas,&nbsp;Jessica A. Dominguez Rieg,&nbsp;Dandan Sun,&nbsp;Adrienne Assmus,&nbsp;Robert A. Fenton,&nbsp;Timo Rieg","doi":"10.1111/apha.70029","DOIUrl":"https://doi.org/10.1111/apha.70029","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The sodium-hydrogen exchanger isoform 1 (NHE1) is important for transepithelial Na⁺/H⁺ transport, intracellular pH, and cell volume regulation. NHE1 also transports Li⁺, preferably compared to NHE3, and the lack of NHE3 does not affect renal Li⁺ clearance. Therefore, we hypothesized that NHE1 plays a critical role in mediating renal Li⁺ effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We generated mice lacking NHE1 in epithelial cells throughout the kidney tubule/collecting duct (NHE1^KS-KO). Physiological phenotyping of NHE1^loxlox and NHE1^KS-KO mice was performed under a control diet and after mice received a LiCl-containing diet for 4 weeks. Tissue was harvested at baseline and at the end of the experimental period for quantification of NHE1 and aquaporin-2 abundances.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In NHE1^loxlox mice, NHE1 localized to the basolateral membrane of the distal parts of the nephron and collecting duct (principal and intercalated cells). No NHE1 was observed in tubules or collecting ducts of NHE1^KS-KO mice, and no physiological differences were observed between genotypes under baseline conditions. While both genotypes developed a urinary concentrating defect in response to Li⁺, NHE1^KS-KO mice drank twice as much, and their urine osmolality was twice as dilute compared with NHE1^loxlox mice. This was associated with greater hypernatremia in NHE1^KS-KO mice. Reduced AQP2 and phosphorylation at serine 256 were observed in NHE1^KS-KO mice. In association with this, AQP2 was more broadly distributed throughout the cytoplasm of NHE1^KS-KO mice, relative to the defined apical membrane AQP2 distribution seen in NHE1^loxlox animals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Lack of NHE1 interferes with the Li⁺ handling in principal cells, resulting in exacerbated Li⁺-induced NDI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 4","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689401","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":"Hypoxia and ischemic stroke modify cerebrovascular tone by upregulating endothelial BK(Ca) channels—Lessons from rat, pig, mouse, and human","authors":"Christian Staehr,&nbsp;Victoria Hinkley,&nbsp;Vladimir V. Matchkov,&nbsp;Rajkumar Rajanathan,&nbsp;Line Mathilde B. Hansen,&nbsp;Yvonne Eiby,&nbsp;Nathan Luque,&nbsp;Ian Wright,&nbsp;Stella T. Bjorkman,&nbsp;Stephanie M. Miller,&nbsp;Rohan S. Grimley,&nbsp;Andrew Dettrick,&nbsp;Kirat Chand,&nbsp;Hong L. Nguyen,&nbsp;Nicole M. Jones,&nbsp;Tim V. Murphy,&nbsp;Shaun L. Sandow","doi":"10.1111/apha.70030","DOIUrl":"10.1111/apha.70030","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>In animal models and human cerebral arteries, the changes in endothelial cell (EC)-large conductance calcium-activated potassium channel (BK_Ca) distribution, expression, and function were determined in hypoxia and ischemic stroke. The hypothesis that hypoxia and ischemic stroke induce EC-BK_Ca in cerebral arteries was examined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Immunohistochemistry analyzed BK_Ca expression in EC and smooth muscle (SM) of the middle-cerebral artery (MCA) from rat, piglet, and mouse, and pial arteriole of human. Pressure myography with pharmacological intervention characterized EC-BK_Ca and TRPV4 function in rat MCA. Electron microscopy determined caveolae density and vessel properties in rat and mouse MCA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In rat, pig, and human cerebral vessels, EC-BK_Ca was absent in normoxia; present after <i>chronic</i> (rat) and <i>acute</i> hypoxia (pig), post-ischemic stroke in human vessels, and after endothelin-1-induced stroke in rats. Mouse MCA EC-BK_Ca expression increased after <i>acute</i> hypoxia. In rat MCA post-hypoxia and stroke, EC and SMC caveolae density increased, with reduced medial thickness, and unchanged diameter. Caveolae and BK_Ca did not colocalize. In rat MCA, iberiotoxin (IbTx) potentiated pressure-induced tone in hypoxia/stroke, but not in normoxia. In normoxia, overall MCA tone was unaffected by endothelial removal, but was increased in hypoxia/stroke, where there was no additive effect of endothelial removal and IbTx on tone. Functional TRPV4 was expressed in EC of rat MCA post-stroke.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In post-hypoxia/stroke, but not in normoxia, EC-BK_Ca contribute to the regulation of MCA tone. Identifying unique up- and downstream signaling mechanisms associated with EC-BK_Ca is a potential therapeutic target to control blood flow post-hypoxia/stroke.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 4","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672973","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":"Les lésions anciennes: Evolution conserves noradrenergic regulation of astroglial homeostatic support","authors":"Alexei Verkhratsky","doi":"10.1111/apha.70032","DOIUrl":"https://doi.org/10.1111/apha.70032","url":null,"abstract":"&lt;p&gt;It is a truth universally acknowledged that every neurone needs an astrocyte to survive and operate. Supportive, homeostatic, and protective neuroglial cells emerged early in evolution together with the centralised nervous system (although some collateral cells of non-neural origin aiding neurones and axons probably existed in even earlier diffuse nervous system of Cnidarians and Ctenophoa). In the February issue of&lt;i&gt;Acta Physiologica&lt;/i&gt;, a team of researchers led by Nina Vardjan and Robert Zorec&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; reveals ancient evolutionary roots of noradrenergic signalling and describes the association with astrocytes, astrocytic Ca&lt;sup&gt;2+&lt;/sup&gt; signalling, and astrocyte physiology.&lt;/p&gt;&lt;p&gt;The very first glial cells were parts of sensory organs, known as sensillas, in invertebrates; incidentally, glial-neuronal sensory organs are common in all species (for example, the organ of Corti, taste buds and olfactory epithelium have ~50% of sustenacular glial cells, which are indispensable for proper sensory function&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt;). The rise of neuroglia reflects the main evolutionary principle of division of functions: neurones are so specialised for the generation of action potentials and synaptic transmission that they cannot sustain the major homeostatic and defensive tasks that define the optimal performance and survival of the nervous tissue. These tasks are fulfilled by neuroglia.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Astroglial cells, which include many types of parenchymal and radial astrocytes, ependymoglia, and astrocyte-like stem cells, are major homeostatic cells in the central nervous system (CNS) that control and execute various functions at all levels of biological organisation, ranging from molecules to organs. In particular, astrocytes control ion homeostasis of the interstitium (also known as ionostasis) and are the main elements of production, clearance, and catabolism of major neurotransmitters and neuromodulators including L-glutamate, GABA, adenosine, catecholamines, and D-serine.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; Astrocytes are electrically non-excitable cells, which employ intercellular ion and second messenger signalling as the substrate of excitability.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; Astrocytic ionic signalling is mediated by Ca&lt;sup&gt;2+&lt;/sup&gt;, Na&lt;sup&gt;+&lt;/sup&gt;, and Cl&lt;sup&gt;−&lt;/sup&gt; &lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt;; the main second messengers are inositol-1,4,5-trisphosphate (InsP&lt;sub&gt;3&lt;/sub&gt;, linked to Ca&lt;sup&gt;2+&lt;/sup&gt; signalling) and cyclic AMP (cAMP) regulating multiple intracellular enzymatic cascades.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; Coordination of ionic and second messenger excitability is critical for astrocytic function in many physiological and pathophysiological contexts.&lt;/p&gt;&lt;p&gt;Noradrenergic innervation of the CNS is mainly associated with the locus coeruleus, the brain stem nucleus containing (in humans) ~20 000–50 000 noradrenergic neurones full of neuromelanin that gives them a dark blue appearance. The locus coeruleus was discovere","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 4","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633032","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":"Cold-induced fibrosis and metabolic remodeling in the turtle (Trachemys scripta) ventricle","authors":"Adam N. Keen,&nbsp;James C. McConnell,&nbsp;John J. Mackrill,&nbsp;John Marrin,&nbsp;Alex J. Holsgrove,&nbsp;Janna Crossley,&nbsp;Alex Henderson,&nbsp;Gina L. J. Galli,&nbsp;Dane A. Crossley II,&nbsp;Michael J. Sherratt,&nbsp;Peter Gardner,&nbsp;Holly A. Shiels","doi":"10.1111/apha.70026","DOIUrl":"https://doi.org/10.1111/apha.70026","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Cardiac fibrosis contributes to systolic and diastolic dysfunction and can disrupt electrical pathways in the heart. There are currently no therapies that prevent or reverse fibrosis in human cardiac disease. However, animals like freshwater turtles undergo seasonal remodeling of their hearts, demonstrating the plasticity of fibrotic remodeling. In <i>Trachemys scripta</i>, cold temperature affects cardiac load, suppresses metabolism, and triggers a cardiac remodeling response that includes fibrosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We investigated this remodeling using Fourier transform infrared (FTIR) imaging spectroscopy, together with functional assessment of muscle stiffness, and molecular, histological, and enzymatic analyses in control (25°C) <i>T. scripta</i> and after 8 weeks of cold (5°C) acclimation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>FTIR revealed an increase in absorption bands characteristic of protein, glycogen, and collagen following cold acclimation, with a corresponding decrease in bands characteristic of lipids and phosphates. Histology confirmed these responses. Functionally, micromechanical stiffness of the ventricle increased following cold exposure assessed via atomic force microscopy (AFM) and was associated with decreased activity of regulatory matrix metalloproteinases (MMPs) and increased expression of MMP inhibitors (TMPs) which regulate collagen deposition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>By defining the structural and metabolic underpinnings of the cold-induced remodeling response in the turtle heart, we show commonalities between metabolic and fibrotic triggers of pathological remodeling in human cardiac disease. We propose the turtle ventricle as a novel model for studying the mechanisms underlying fibrotic and metabolic cardiac remodeling.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 4","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143622666","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":"Editorial related to the special issue: “Extrarenal functions of the renin-angiotensin-system”","authors":"Rhian M. Touyz,&nbsp;U. Muscha Steckelings","doi":"10.1111/apha.70027","DOIUrl":"https://doi.org/10.1111/apha.70027","url":null,"abstract":"&lt;p&gt;A recent collection of five review articles published in this journal highlights some state-of-the-art research that has been presented at the Gordon Research Conference on Angiotensin in February 2024. These articles feature a broad spectrum of research areas related to the renin-angiotensin-aldosterone system (RAAS), authored by experts in the field.&lt;/p&gt;&lt;p&gt;Two articles of this collection focus on novel approaches for the understanding of angiotensin receptor signaling.&lt;span&gt;&lt;sup&gt;1, 2&lt;/sup&gt;&lt;/span&gt; Gironacci and Bruna-Haupt elucidate how RAAS receptor dimerization with other RAAS- or non-RAAS receptors alters receptor affinity, trafficking, signaling, and biological function.&lt;span&gt;&lt;sup&gt;1, 3&lt;/sup&gt;&lt;/span&gt; For example, cross-inhibition is a dimer-specific phenomenon leading to antagonism of one receptor in a dimer by an antagonist specific for the other receptor in the dimer. New drug candidates are in development that target receptor dimers instead of single receptors, making use of dimer-specific crosstalk between receptors. However, the authors also point out that receptor dimerization and its functional consequences are understudied, which means that many drug actions caused by receptor dimerization (e.g. AT&lt;sub&gt;1&lt;/sub&gt;-receptor antagonism by beta&lt;sub&gt;2&lt;/sub&gt;-adrenergic receptor antagonists&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt;) are underestimated and their potential clinical consequences unknown and not taken into therapeutic consideration.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Verano-Braga, Steckelings, and co-authors highlight new approaches to study angiotensin receptor signaling through quantitative phosphoproteomics, i.e. the monitoring of all protein phospho- and dephosphorylation events in a cell, as a hypothesis-generating method for identifying so-far unknown angiotensin receptor signaling mechanisms.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; The article reviews the literature on phosphoproteomics addressing biased signaling, beta-arrestin-dependent AT&lt;sub&gt;1&lt;/sub&gt;-receptor (AT&lt;sub&gt;1&lt;/sub&gt;R) signaling, or signaling of receptors of the protective arm of the RAAS, namely AT&lt;sub&gt;2&lt;/sub&gt;-receptor (AT&lt;sub&gt;2&lt;/sub&gt;R), receptor Mas, and Mas-related G-protein coupled receptor D (MrGD). While all angiotensin receptors are categorized as being G-protein coupled receptors (GPCRs), receptors of the protective arm of the RAAS usually do not induce “classical” GPCR-mediated signaling cascades but rather unconventional, and in large part unknown, pathways, which makes a non-targeted methodology for their identification a useful approach. Extrarenal effects of the protective arm of the RAAS identified by phosphoproteomics include anti-senescence effects (e.g. inhibition of mTOR signaling), effects on histone acetylation with impact on cell cycle control and tumor-suppressor (p53) actions, or effects on glucose homeostasis.&lt;span&gt;&lt;sup&gt;5-8&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;The article highlights future applications of this technology, such as the exploration of cell-specific angiotensin receptor signalin","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 4","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143622529","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":"Introducing a special issue: Acid–base regulation and sensing in health and disease","authors":"Stine Falsig Pedersen,&nbsp;Ebbe Boedtkjer","doi":"10.1111/apha.70021","DOIUrl":"https://doi.org/10.1111/apha.70021","url":null,"abstract":"&lt;p&gt;Cell metabolism continuously generates acid, primarily in the form of H&lt;sup&gt;+&lt;/sup&gt; from fermentation and CO&lt;sub&gt;2&lt;/sub&gt; from oxidative phosphorylation. However, the normal physiological functions at all levels of biological organization depend on pH being regulated within narrow ranges. The homeostatic regulation of acid–base status is therefore fundamentally important in virtually all aspects of physiology. At the cellular and organellar level, ion transport proteins import and export acids and bases across membranes, and passive H&lt;sup&gt;+&lt;/sup&gt;-buffering systems limit changes in pH upon acid–base challenges and facilitate H&lt;sup&gt;+&lt;/sup&gt; movement to and from sites of production and transport. Signaling events—initiated, for example, by H&lt;sup&gt;+&lt;/sup&gt;-sensing G-protein coupled receptors, ion channels, and transmembrane or soluble HCO&lt;sub&gt;3&lt;/sub&gt;&lt;sup&gt;−&lt;/sup&gt;-sensing proteins&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;—control the expression and activity of the pH regulatory systems and produce functional adaptations in response to acid–base disturbances. In vertebrates, acid extruded from cells enters the vasculature and moves via the blood to the lungs and kidneys where it is finally eliminated.&lt;/p&gt;&lt;p&gt;Given the pivotal physiological importance of acid–base regulation and its disturbances, it is not surprising that key studies on this topic have been published in &lt;i&gt;Acta Physiologica&lt;/i&gt;. Over 120 years ago in 1904, when &lt;i&gt;Acta Physiologica&lt;/i&gt; was the Skandinavisches Archiv Für Physiologie, August Krogh published pioneering organism-level experiments on cutaneous respiration, that is, the elimination of CO&lt;sub&gt;2&lt;/sub&gt; across the frog skin.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Already then, studies of the physiological relevance of pH spanned from organism to molecule, as the same year, Christian Bohr, with Hasselbalch and Krogh, revealed how variation in CO&lt;sub&gt;2&lt;/sub&gt; levels (with associated changes in pH) alter O&lt;sub&gt;2&lt;/sub&gt; binding to hemoglobin.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; This essential observation, widely known as the Bohr effect, was the first demonstration that CO&lt;sub&gt;2&lt;/sub&gt;/H&lt;sup&gt;+&lt;/sup&gt; binding can alter protein function in a physiologically relevant manner. Since then, the concept of protonation as a posttranslational modification has been studied in great molecular detail. Important examples&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; now illustrate how pH regulates the function of proteins with protonatable amino acid residues, from enzymes to ion channels to cell adhesion proteins. Thus, we now appreciate a complex landscape of pH sensitivity that extends far beyond the &lt;i&gt;bona fide&lt;/i&gt; H&lt;sup&gt;+&lt;/sup&gt; sensing receptors.&lt;/p&gt;&lt;p&gt;More recent work highlights the essential roles that disturbances in acid–base regulation and sensing play in several pathophysiological conditions. This includes solid tumors characterized by extracellular accumulation of acidic metabolic waste products that have been shown to favor cancer progression and limit anti-cancer immunity.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; The","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 4","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143622526","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":"Slow rather than fast calcium events encode physiological inputs and propagate within islets: Lessons from ultrafast imaging on acute pancreatic tissue slices","authors":"Matthieu Raoux,&nbsp;Dorian Chapeau,&nbsp;Jochen Lang","doi":"10.1111/apha.70028","DOIUrl":"https://doi.org/10.1111/apha.70028","url":null,"abstract":"&lt;p&gt;Pancreatic islets are micro-organs, mainly composed of insulin-secreting β cells, which play a central role in nutrient homeostasis and diabetes. They can be viewed as “mini-brains” of glucose homeostasis, as they present networks of excitable cells that express numerous neural proteins&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; and integrate nutritional, hormonal, and neuronal inputs in real time to continuously provide the amount of insulin required to cover physiological needs. In type 2 diabetes, which accounts for 90% of diabetes cases, both individual and collective β cell activities are impaired. Consequently, many groups have attempted to explore the single-cell and multicellular behavior of β cells for years using either intracellular electrophysiology, which offers high-temporal resolution but is invasive and limited to one cell, or optical methods, mainly Ca&lt;sup&gt;2+&lt;/sup&gt; imaging, which provides excellent spatial resolution but very limited temporal resolution, with a typical sampling rate of 0.5–2 Hz. This temporal resolution allows the detection of only slow Ca&lt;sup&gt;2+&lt;/sup&gt; events, namely Ca&lt;sup&gt;2+&lt;/sup&gt; bursts, and prevents the detection of fast Ca&lt;sup&gt;2+&lt;/sup&gt; events, namely Ca&lt;sup&gt;2+&lt;/sup&gt; spikes, although Ca&lt;sup&gt;2+&lt;/sup&gt; spikes represent the trigger for insulin granule exocytosis. In this issue of &lt;i&gt;Acta Physiologica&lt;/i&gt;, Dolenšek et al. present high-temporal-resolution optical measurements (40–178 Hz) of selected islet areas using line scan confocal imaging on acute pancreas slices (i.e. in their native environment) in response to physiological levels of glucose and acetylcholine (Figure 1).&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Their detailed characterization of both Ca&lt;sup&gt;2+&lt;/sup&gt; bursts and spikes at individual and collective levels offers new insights into the respective roles of these signals in islets, their encoding of glucose levels and cholinergic inputs, and their propagation within the micro-organ, and finally opens new perspectives for understanding islet “mini-brain” networks deregulation in diabetes.&lt;/p&gt;&lt;p&gt;The classical approach to measure spikes with sufficient temporal resolution in islets has so far been the perforated patch-clamp.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; However, this complex and invasive technique allows measurements at the single-cell level rather than the multicellular level and only for a few minutes, whereas islets are stimulated for 2–3h during digestion. Very few ultrafast Ca&lt;sup&gt;2+&lt;/sup&gt; measurements on isolated β cells&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; or whole islets&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; had been performed prior to this study, but they were limited in time and did not include spike analysis. Dolenšek et al. show now the correspondence between electrical and Ca&lt;sup&gt;2+&lt;/sup&gt; events,&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; consequently, their work paves the way for multicellular optical approaches as an alternative to patch-clamp for laboratories lacking the necessary equipment or expertise.&lt;/p&gt;&lt;p&gt;Their work provides new insights into islet biology ","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 4","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143622295","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}