Acta Physiologica最新文献

{"title":"New Editor-in-Chief for Acta Physiologica","authors":"Tobias Wang","doi":"10.1111/apha.70044","DOIUrl":"https://doi.org/10.1111/apha.70044","url":null,"abstract":"<p>I assumed the role of Editor-in-Chief of <i>Acta Physiologica</i> with equal measures of awe and pride at the very start of 2025. Awe because I must fill the shoes of my predecessor Professor Pontus Persson [<span>1</span>], who competently led the journal for more than a decade with great dedication and ability. The pride is obviously instilled from becoming part of an almost 140-year physiology legacy at the highest level possible. <i>Acta Physiologica</i> is indeed ranked amongst the world's best general physiology journals and enjoys widespread respect amongst authors and readers in all physiological disciplines.</p><p>In addition to awe and pride, I confess that the role as EiC for <i>Acta Physiologica</i> also instills a component of anxiety. Academic publishing is currently entering troubled waters where the old supertankers, that is, the society journals, are in danger of being derailed by predatory journals that weigh financial interest higher than the pursuit of knowledge and the classic academic virtues. The society journals, however, have much to offer, and <i>Acta Physiologica</i>, for example, channels revenues into academic activities with support to meetings, conferences, and travel grants. <i>Acta Physiologica</i> therefore contributes to building the physiological community at all stages in an academic career.</p><p>As an additional merit, <i>Acta Physiologica</i> has been the official <i>Journal of the Federation of European Physiological Societies</i> (FEPS) for more than three decades, and we are currently expanding our editorial board to be more international in line with the ongoing and welcome internationalization of physiological sciences.</p><p>I firmly believe that general physiology journals, such as <i>Acta Physiologica</i>, that cover many processes within all bodily organs and tissues are important because they emphasize the integration of processes that span from molecular structures to the whole organism. In addition to the “vertical” integration at various levels of biological organization, physiology also arises from the “horizontal” interplay between organ systems. Both vertical and horizontal interactions are of paramount importance for animals and humans to maintain homeostasis during normal behaviors and physiological states, including sleep [<span>2</span>], exercise [<span>3</span>], digestion [<span>4</span>], and pregancy [<span>5</span>] and to understand how we respond to environmental perturbances, such as hypoxia [<span>6</span>], hypercapnia [<span>7</span>], or extreme temperatures [<span>8</span>]. In combination with diurnal and annual cycles [<span>9, 10</span>], the homeostatic regulation by virtue of endocrine and neural mechanisms of humans and animals is therefore as exciting as ever!</p><p>In my own research, I am highly motivated to understand organismal function, and I characterize myself as an integrative physiologist that seeks to understand the unifying principles in physiology. Wit","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70044","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770035","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":"Glucose absorption by isolated, vascularly perfused rat intestine: A significant paracellular contribution augmented by SGLT1 inhibition","authors":"Cecilie Bæch-Laursen,&nbsp;Rune Kuhre Ehrenreich,&nbsp;Ida Marie Modvig,&nbsp;Simon Veedfald,&nbsp;Jens Juul Holst","doi":"10.1111/apha.70033","DOIUrl":"https://doi.org/10.1111/apha.70033","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Intestinal glucose transport involves SGLT1 in the apical membrane of enterocytes and GLUT2 in the basolateral membrane. In vivo studies have shown that absorption rates appear to exceed the theoretical capacity of these transporters, suggesting that glucose transport may occur via additional pathways, which could include passive mechanisms. The aim of the study was to investigate glucose absorption in an in vitro model, which has proven useful for endocrine studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We studied both transcellular and paracellular glucose absorption in the isolated vascularly perfused rat small intestine. Glucose absorbed from the lumen was traced with ¹⁴C-<span>d</span>-glucose, allowing sensitive and accurate quantification. SGLT1 and GLUT2 activities were blocked with phlorizin and phloretin. ¹⁴C-<span>d</span>-mannitol was used as an indicator of paracellular absorption.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our results indicate that glucose absorption in this model involves two transport mechanisms: transport mediated by SGLT1/GLUT2 and a paracellular transport mechanism. Glucose absorption was reduced by 60% when SGLT1 transport was blocked and by 80% when GLUT2 was blocked. After combined luminal SGLT1 and GLUT2 blockade, ~30% of glucose absorption remained. <span>d</span>-mannitol absorption was greater in the proximal small intestine compared to the distal small intestine. Unexpectedly, mannitol absorption increased markedly when SGLT1 transport was blocked.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In this model, glucose absorption occurs via both active transcellular and passive paracellular transport, particularly in the proximal intestine, which is important for the understanding of, for example, hormone secretion related to glucose absorption. Interference with SGLT1 activity may lead to enhanced paracellular transport, pointing to a role in the regulation of the latter.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778174","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":"Deficiency of the Synaptic Adhesion Protein Leucine-Rich Repeat Transmembrane Protein 4 Like 1 Affects Anxiety and Aggression in Zebrafish","authors":"Eva Tatzl,&nbsp;Giulia Petracco,&nbsp;Isabella Faimann,&nbsp;Marco Balasso,&nbsp;Agnes Anna Mooslechner,&nbsp;Thomas Bärnthaler,&nbsp;Giovanny Rodriguez-Blanco,&nbsp;Florian Reichmann","doi":"10.1111/apha.70042","DOIUrl":"https://doi.org/10.1111/apha.70042","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Leucine-rich repeat transmembrane proteins (LRRTMs) are synaptic adhesion proteins that regulate synapse development and function. They interact transsynaptically with presynaptic binding partners to promote presynaptic differentiation. Polymorphisms of <i>LRRTM4</i>, one of the four members of this protein family, have been linked to multiple neuropsychiatric disorders and childhood aggression, but the underlying mechanisms and physiological function of LRRTM4 during behavior are currently unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To characterize the role of this gene for brain function, we combined a battery of behavioral assays with transcriptomic and metabolomic analyses, using zebrafish as a model system.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our findings revealed that <i>lrrtm4l1</i>, a brain-specific zebrafish orthologue of human <i>LRRTM4</i>, exhibits a brain region-specific expression pattern similar to humans, with strong expression in the dorsal telencephalon, a brain area critical for regulating emotional-affective and social behavior. <i>lrrtm4l1</i>^−/− zebrafish displayed heightened anxiety and reduced aggression, while locomotion and social behavior remained unaffected by the gene knockout. Transcriptomic analysis of the telencephalon identified over 100 differentially expressed genes between wild-type and mutant zebrafish and an enrichment of pathways related to synaptic plasticity and neuronal signaling. The brain metabolome of <i>lrrtm4l1</i>^−/− zebrafish showed multiple alterations, particularly in the dopaminergic and adenosinergic neurotransmitter systems.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings suggest that LRRTMs may have functions beyond their established role in excitatory synapse development, such as the regulation of neurotransmission and behavior. Targeting LRRTM4 therapeutically may thus be an interesting novel approach to alleviate excessive aggression or anxiety associated with a number of neuropsychiatric conditions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770034","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":"16/8 intermittent fasting in mice protects from diet-induced obesity by increasing leptin sensitivity and postprandial thermogenesis","authors":"Adriano Cleis Arruda,&nbsp;Raisa Brito Santos,&nbsp;Leandro Ceotto Freitas-Lima,&nbsp;Alexandre Budu,&nbsp;Mauro Sergio Perilhão,&nbsp;Frederick Wasinski,&nbsp;Gabriel Melo Arthur,&nbsp;Roger Rodrigues Guzmán,&nbsp;Guilherme Gomes,&nbsp;Joao Bosco Pesquero,&nbsp;André Souza Mecawi,&nbsp;Michael Bader,&nbsp;Alexandre Castro Keller,&nbsp;José Donato Junior,&nbsp;Willian Tadeu Festuccia,&nbsp;Marcelo A. Mori,&nbsp;Ronaldo Carvalho Araujo","doi":"10.1111/apha.70036","DOIUrl":"https://doi.org/10.1111/apha.70036","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To evaluate the molecular mechanisms involved in intermittent fasting 16/8 (16/8 IF), a widespread dietary practice adopted worldwide that consists of 16 h of fasting and 8 h of feeding.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Obese mice were fasted daily from 6 am to 10 pm. Food intake, body weight, and energy expenditure were measured. Molecular mechanisms were investigated using ELISA, western blot, and qPCR of white and brown adipose tissues. Glucose homeostasis was also evaluated. Ucp1 knockout and ob/ob mice were utilized.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The 16/8 IF regimen improved glucose homeostasis and reduced body weight, food intake, and overall adiposity. Postprandial VO₂, heat production, brown adipose tissue (BAT) temperature, and ketone bodies increased with 16/8 IF. Postprandial thermogenesis induced by 16/8 IF was abolished in mice after BAT denervation or Ucp1 deletion. Serum leptin levels were elevated, and most metabolic effects of 16/8 IF were absent in leptin-deficient ob/ob mice. Additionally, leptin sensitivity increased in mice exposed to 16/8 IF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The 16/8 IF regimen can improve metabolism, with findings underscoring the role of enhanced leptin action in inhibiting food intake and promoting postprandial thermogenesis during 16/8 IF.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778170","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":"Exercise training restores longevity-associated tryptophan metabolite 3-hydroxyanthranilic acid levels in middle-aged adults","authors":"Niklas Joisten,&nbsp;Marcel Reuter,&nbsp;Friederike Rosenberger,&nbsp;Andreas Venhorst,&nbsp;Marie Kupjetz,&nbsp;David Walzik,&nbsp;Alexander Schenk,&nbsp;Adrian McCann,&nbsp;Per Magne Ueland,&nbsp;Tim Meyer,&nbsp;Philipp Zimmer","doi":"10.1111/apha.70041","DOIUrl":"https://doi.org/10.1111/apha.70041","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Recent pre-clinical evidence suggests that the tryptophan metabolite 3-hydroxyanthranilic acid (3-HAA) and the related enzyme activity along the kynurenine metabolic pathway (KP) are associated with lifespan extension. We aimed to translate these findings into humans and expose exercise training as a potential non-pharmacological intervention to modulate this metabolic hub.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To explore whether recent pre-clinical findings might also be of relevance for humans, we analyzed the evolutionary conservation of KYNU and HAAO, the two core KP enzymes associated with 3-HAA. In a cross-sectional analysis of young-to-middle-aged adults (<i>N</i> = 84), we examined potential associations of serum 3-HAA and its precursor anthranilic acid with age. We then investigated whether 26 weeks of endurance exercise (increasing intensity (INC) during the intervention period (<i>n</i> = 17) vs. conventional moderate continuous training (CON) matched for energy expenditure (<i>n</i> = 17)) impacted 3-HAA levels, related metabolic ratios, and other KP metabolites.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We demonstrate that the core KP enzymes associated with 3-HAA are evolutionarily conserved in humans. Serum 3-HAA and its precursor anthranilic acid were consistently associated with age in young-to-middle-aged adults. Both exercise modes tested induced an increase in 3-HAA levels of 134% (<i>p</i> &lt; 0.001) and 85% (<i>p</i> &lt; 0.001) compared with baseline, respectively, without a significant time*group interaction effect.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We translate the association between systemic 3-HAA levels and age from animal models into humans and highlight longer-term exercise training as an efficient strategy to boost systemic 3-HAA levels in middle-aged adults. Our findings open promising research avenues concerning the mediating role of 3-HAA in training adaptations, health, and longevity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143761841","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":"Identification of a new gain-of-function variant p.N536Y of KCNMA1 associated with PNKD3 in the Chinese population","authors":"Yufeng Huang,&nbsp;Lina Liang,&nbsp;Xuebin Xu,&nbsp;Yin Liu,&nbsp;Feng Gao,&nbsp;Xuelian He,&nbsp;Qing K. Wang","doi":"10.1111/apha.70039","DOIUrl":"https://doi.org/10.1111/apha.70039","url":null,"abstract":"&lt;p&gt;The high-conductance calcium- and voltage-dependent K&lt;sup&gt;+&lt;/sup&gt; potassium channels (BK channel) are important for the electrical excitation of nervous and muscular tissues.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; In 2005, we identified the first disease-causing variant in the gene encoding the α-subunit &lt;i&gt;KCNMA1&lt;/i&gt; (p.D434G) in this channel and showed that the gain-of-function (GOF) variant of &lt;i&gt;KCNMA1&lt;/i&gt; causes paroxysmal nonkinesigenic dyskinesia with or without generalized epilepsy (PNKD3, MIM #609446).&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; In 2019, we showed that loss of function variants cause Liang-Wang syndrome (MIM #618729) with neurodevelopmental dysfunction of developmental delay, impaired intellectual development, poor or absent language ability, epilepsy, ataxia, and other multi-organ defects.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; Both PNKD3 and Liang-Wang syndrome are phenotypically heterogeneous, and detailed genotype–phenotype correlation is critical to genetic testing and counseling.&lt;/p&gt;&lt;p&gt;To date, only three &lt;i&gt;KCNMA1&lt;/i&gt; variants were shown to cause PNKD3, including p.D434G, p.N995S, and p.N536H.&lt;span&gt;&lt;sup&gt;2-10&lt;/sup&gt;&lt;/span&gt; Here, we report &lt;i&gt;KCNMA1&lt;/i&gt; variants in two new Chinese patients, including a novel variant p.N536Y in the same amino acid as p.N536H and the previously reported variant N995S. In the first patient, PNKD was diagnosed at an age of 2 years and 10 months (Figure 1A), but bilateral hydronephrosis was found at birth. Her developmental milestones were normal during the first 6 months, but then began to slow, and were manifested as low alertness, delayed language acquisition, and poor ability to communicate. When 6 months old, she was admitted to an intensive care unit (ICU) due to high potassium and low sodium, and she developed paroxysmal dyskinesia at the age of one that was successfully treated with carbamazepine, topiramate, and nitrazepam that reduced the frequency and severity of attacks. Whole exome sequencing, also of her parents, identified the de novo &lt;i&gt;KCNMA1&lt;/i&gt; variant c.1606A&gt;T, p.N536Y (NM_002247) (Figure 1A,B). The N536 amino acid is highly conserved among different species through evolution (Figure 1C) and located in the Ca&lt;sup&gt;2+&lt;/sup&gt;-sensing RCK1 domain (Figure 1D).&lt;/p&gt;&lt;p&gt;Patch-clamping revealed that variant p.N536Y significantly increases the mean amplitude of &lt;i&gt;I&lt;/i&gt;&lt;sub&gt;&lt;i&gt;BK&lt;/i&gt;&lt;/sub&gt; (Figure 1E) and shifts the G-V curves to more negative potentials by −67 mV at 10 μM [Ca&lt;sup&gt;2+&lt;/sup&gt;] (Figure 1E,F), demonstrating that &lt;i&gt;KCNMA1&lt;/i&gt; variant p.N536Y is a functional gain-of-function variant. Compared with BK-WT channels, the G-V curves of mutant channels shifted to more negative potentials at all Ca&lt;sup&gt;2+&lt;/sup&gt; concentrations. The shift was approximately −105 mV in the presence of 0 μM intracellular [Ca&lt;sup&gt;2+&lt;/sup&gt;], −78 mV in the presence of 1 μM intracellular [Ca&lt;sup&gt;2+&lt;/sup&gt;], and approximately −67 mV in the presence of 10 μM intracellular [Ca&lt;sup&gt;2+&lt;/sup&gt;] (Figure 1G). The data suggest that variant p.N536Y caus","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741041","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":"Lactate orchestrates metabolic hemodynamic adaptations through a unique combination of venocontraction, artery relaxation, and positive inotropy","authors":"Casper Homilius,&nbsp;Jacob M. Seefeldt,&nbsp;Jakob Hansen,&nbsp;Roni Nielsen,&nbsp;Frank V. de Paoli,&nbsp;Ebbe Boedtkjer","doi":"10.1111/apha.70037","DOIUrl":"https://doi.org/10.1111/apha.70037","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>H⁺ facilitates metabolic blood flow regulation while negatively impacting cardiac contractility. Cardiovascular consequences of conjugate bases accumulating alongside H⁺ remain unclear. Here, we evaluate the cardiovascular effects of nine prominent carboxylates—particularly lactate, 3-hydroxybutyrate, and butyrate—linked to metabolic and microbial activity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Comparing the actions of pH-adjusted Na-carboxylates to equiosmolar NaCl, we study arteries and veins isolated from healthy rats and humans with ischaemic heart disease, isolated perfused rat hearts, and rat cardiovascular function in vivo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The tested carboxylates generally relax arteries and veins. L-lactate relaxes human and rat arteries up to 70% (EC₅₀ = 10.1 mM) and rat brachial and mesenteric veins up to 30% of pre-contractions, yet stands out by augmenting contractions of rat femoral, saphenous, and lateral marginal veins and human internal thoracic and great saphenous veins up to 50%. D-lactate shows only minor actions. In isolated perfused hearts, 10 mM L-lactate increases coronary flow (17.1 ± 7.7%) and left ventricular developed pressure (10.1 ± 3.0%) without affecting heart rate. L-lactate infusion in rats—reaching 3.7 ± 0.3 mM in the circulation—increases left ventricular end-diastolic volume (11.3 ± 2.8%), stroke volume (22.6 ± 3.0%), cardiac output (23.4 ± 3.5%), and ejection fraction (10.6 ± 2.0%), and lowers systemic vascular resistance (34.1 ± 3.7%) without influencing blood pressure or heart rate. The ketone body 3-hydroxybutyrate causes lactate accumulation and elevates left ventricular end-diastolic volume in vivo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Carboxylate metabolites generally relax arteries and veins. L-lactate relaxes arteries, lowering systemic vascular resistance, causes preferential venocontraction with increased ventricular diastolic filling, and elevates cardiac contractility and cardiac output. We propose that L-lactate optimizes cardiovascular function during metabolic disturbances.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741103","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":"Neuronal activity modulates the expression of secretagogin, a Ca2+ sensor protein, during mammalian forebrain development","authors":"János Hanics,&nbsp;Evgenii O. Tretiakov,&nbsp;Roman A. Romanov,&nbsp;Anna Gáspárdy,&nbsp;Zsófia Hevesi,&nbsp;Robert Schnell,&nbsp;Tibor Harkany,&nbsp;Alán Alpár","doi":"10.1111/apha.70031","DOIUrl":"https://doi.org/10.1111/apha.70031","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Because of their stable expression, some EF-hand Ca²⁺-binding proteins are broadly used as histochemical markers of neurons in the nervous system. Secretagogin is a member of “neuron-specific” Ca²⁺-sensor proteins, yet variations in its expression due, chiefly, to neuronal activity remain ambiguous. We aimed to fill this gap of knowledge both in its use as a cell identity marker and for mechanistic analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We mapped secretagogin distribution in human foetal forebrains. Then, <i>Scgn</i>-iCre::Ai9 mice in conjunction with single-cell RNA-seq were used to molecularly characterize cortical secretagogin-expressing neurons. Besides the in vitro manipulation of both SH-SY5Y neuroblastoma cells and primary cortical cultures from foetal mice, the activity dependence of secretagogin expression was also studied upon systemic kainate administration and dark rearing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the mammalian brain, including humans, both transient and stable secretagogin expression sites exist. In the cerebral cortex, we identified deep-layer pyramidal neurons with lifelong expression of secretagogin. Secretagogin expression was affected by neuronal activity: it was delayed in a cohort of human foetuses with Down's syndrome relative to age-matched controls. In mice, dark rearing reduced secretagogin expression in the superior colliculus, a midbrain structure whose development is dependent on topographic visual inputs. In contrast, excitation by both KCl exposure of SH-SY5Y cells and primary cortical neurons in vitro and through systemic kainate administration in mice increased secretagogin expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We suggest that secretagogin expression in neurons is developmentally regulated and activity dependent.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70031","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741479","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":"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}