Acta Physiologica最新文献

{"title":"Adhesion GPCRs as Hot Targets for Obesity.","authors":"Martin Jastroch, Michaela Keuper","doi":"10.1111/apha.70225","DOIUrl":"https://doi.org/10.1111/apha.70225","url":null,"abstract":"","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 5","pages":"e70225"},"PeriodicalIF":5.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147757863","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":"When Citrate Accumulates: A New Metabolic Driver of Renal Lipotoxicity in Chronic Kidney Disease.","authors":"Nils J Færgeman","doi":"10.1111/apha.70222","DOIUrl":"10.1111/apha.70222","url":null,"abstract":"","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 5","pages":"e70222"},"PeriodicalIF":5.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147669423","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":"Lack of Kir4.1 in the Distal Convoluted Tubule Causes ENaC Hyperactivity During K⁺ Restriction Leading to Hypokalemia.","authors":"Zhong-Xiuzi Gao, Yuan-Yuan Yang, Rui-Juan Zhang, Fei-Hong Li, Ya-Fan Mu, Ting-Ting Shu, Zi-Hui Mao, Qing Zhang, Shao-Kang Pan, Dong-Wei Liu, Zhang-Suo Liu, Peng Wu","doi":"10.1111/apha.70221","DOIUrl":"10.1111/apha.70221","url":null,"abstract":"<p><strong>Aim: </strong>Loss-of-function mutations in KCNJ10, encoding Kir4.1, cause EAST/SeSAME syndrome, with renal salt-wasting tubulopathy and hypokalemia. We hypothesized that Kir4.1 deletion specifically in the distal convoluted tubule (DCT) stimulates ENaC activity via the mammalian target of rapamycin (mTOR)-dependent mechanisms, contributing to hypokalemia.</p><p><strong>Methods: </strong>Metabolic cages, electrophysiology, immunoblotting, immunostaining, and in vivo diuretic response experiments were used to examine biochemical parameters, Kir4.1/Kir5.1 activity, NCC and ENaC function in the DCT-specific Kir4.1 knockout (DCT-Kir4.1 KO) mice under normal or K⁺ restriction conditions.</p><p><strong>Results: </strong>DCT-Kir4.1 KO mice exhibited impaired basolateral K⁺ channel and NCC activity, enhanced ENaC activity, and mild hypokalemia. Amiloride treatment induced similar natriuresis and kaliuresis in DCT-Kir4.1 KO and kidney-specific Kir4.1 KO mice, but had minimal effects in collecting system Kir4.1 KO mice, suggesting high ENaC activity following Kir4.1 deletion in the DCT. Notably, severe hypokalemia, along with upregulated ENaC expression and activity, was observed in DCT-Kir4.1 KO mice under dietary K⁺ restriction. Patch-clamp experiments further revealed elevated ENaC currents in the DCT2 of KO mice on a low-K⁺ diet, independent of aldosterone levels. Inhibition of mTOR with AZD8055 reduced SGK1/Nedd4-2 phosphorylation, cleaved α-ENaC expression, and DCT2 ENaC currents, suggesting a role for mTOR in ENaC hyperactivity in K⁺-restricted DCT-Kir4.1 KO mice. This notion was also supported by the upregulated Rictor expression observed in the isolated DCT of these KO mice.</p><p><strong>Conclusion: </strong>We conclude that Kir4.1 deletion drives ENaC hyperactivity in the DCT via the mTORC2-dependent SGK1/Nedd4-2 signaling pathway, promoting low potassium diet-induced hypokalemia.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 5","pages":"e70221"},"PeriodicalIF":5.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147669403","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":"Microglia-Specific K2P Channel THIK-1: Structure, Function, and Therapeutic Potential","authors":"Yoonsub Kim,&nbsp;Bo Hyun Lee,&nbsp;Byeonggyu Ahn,&nbsp;Eun-A Ko,&nbsp;Dawon Kang","doi":"10.1111/apha.70224","DOIUrl":"10.1111/apha.70224","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The tandem pore domain halothane-inhibited potassium (THIK-1) channel is a member of the two-pore domain potassium (K2P) channel family and plays a critical role in maintaining the resting membrane potential. THIK-1 has emerged as a key regulator of microglial physiology and neuroimmune signaling. With the rapid accumulation of structural, electrophysiological, and functional evidence, there is an increasing need for an integrated understanding of THIK-1 in the context of microglial biology and disease.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Aims&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This review provides a comprehensive synthesis of the structural, regulatory, and functional properties of THIK-1, with a particular focus on its roles in microglial physiology, neuroimmune signaling, and central nervous system (CNS) pathologies.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Materials and Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We conducted a comprehensive review of recent literature, including electrophysiological, molecular, and structural studies, with particular emphasis on cryo-electron microscopy findings, pharmacological modulation, and disease-associated functional analyses.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;THIK-1 is selectively enriched in microglia and contributes to essential cellular processes, including surveillance motility, synaptic pruning, and inflammasome activation. Its high constitutive activity makes it a dominant determinant of the microglial membrane potential. Structural studies have identified key features, including a lipid-interacting pocket and a cytoplasmic gate, which underlie lipid- and anesthetic-mediated regulation. Functionally, THIK-1-mediated K⁺ efflux is required for NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome activation and pyroptosis. Accumulating evidence links THIK-1 to major CNS disorders, including neuroinflammation, neurodegeneration (e.g., Alzheimer's and Parkinson's diseases), and psychiatric disorders.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Discussion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The convergence of structural, electrophysiological, and immunological findings positions THIK-1 as a central regulator of neuroimmune signaling. Integration of these findings provides new insights into how ion channel activity shapes microglial function and disease processes.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;THIK-1 represents a critical nexus between ion channel biophysics and neuroimmune dysfunction. A comprehensive understanding of its regulation and function su","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147669390","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":"Adipose-Specific Overexpression of ADGRA3 Induces UCP1-Dependent Thermogenesis to Ameliorate Obesity and Improve Glucose Homeostasis","authors":"Ze-Wei Zhao,&nbsp;Jin Li,&nbsp;Zhonghan Yang","doi":"10.1111/apha.70223","DOIUrl":"10.1111/apha.70223","url":null,"abstract":"","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147669281","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":"miR-221 Mediates the Regulation of Phospholamban Expression and Cardiac Contractility by ZBTB20","authors":"Qiu-Xiao Ren,&nbsp;Ya-Jin Liu,&nbsp;Ping Wang,&nbsp;Xiaowei Song,&nbsp;Qian Zhao,&nbsp;Ya-Nan Cao,&nbsp;Ru-Tai Hui,&nbsp;Huang-Tian Yang,&nbsp;Yi Zhu,&nbsp;Chun-Chun Wei,&nbsp;An-Jing Ren,&nbsp;Weiping J. Zhang","doi":"10.1111/apha.70217","DOIUrl":"10.1111/apha.70217","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Phospholamban (PLN) is a key regulator of sarco-endoplasmic reticulum calcium ATPase (SERCA) activity and myocardial contractility, but its expression control remains incompletely understood. This study seeks to clarify the molecular mechanism of PLN regulation and its functional relevance in cardiac physiology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>Using cardiomyocyte-specific ZBTB20 knockout (CZB20KO) mice and primary cardiomyocytes, we demonstrated that ZBTB20 deficiency significantly reduced PLN protein at a higher magnitude than its mRNA levels, accompanied by a marked increase in the expression levels of miR-221 and miR-222 derived from the same gene cluster. Cardiomyocyte-specific deletion of miR-221/222 alone did not affect cardiac PLN expression in the mice, but fully restored the expression of PLN protein and the basal cardiac contractility in the context of ZBTB20 deficiency, as evidenced by normal left ventricular ejection fraction and fractional shortening compared to control mice. Through luciferase reporter assays with 3′UTR binding site mutagenesis and gain/loss-of-function experiments, we identified miR-221 but not its paralog miR-222 as a direct regulator of PLN by targeting its 3′UTR of mRNA. Moreover, cardiomyocyte-specific overexpression of miR-221 in mice led to a reduction in cardiac PLN protein levels. ChIP assay did not reveal significant binding of ZBTB20 to the miR-221/222 gene cluster.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study identifies miR-221 as a novel regulator of cardiac PLN expression and a mediator of the regulation of PLN by ZBTB20. Thus this work provides insights into the regulation of basal contractility and functional reserve of the heart.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147637407","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":"Low-Salt Diet Induces Claudin-3 Expression and Drives Adaptive Changes in Collecting Duct of Claudin-3-Deficient Mice","authors":"Ali Sassi,&nbsp;Alexandra Chassot,&nbsp;Sara Jellali,&nbsp;Nicolas Liaudet,&nbsp;Ana Polat,&nbsp;Felix Baier,&nbsp;Deborah Stroka,&nbsp;Mikio Furuse,&nbsp;Eric Feraille","doi":"10.1111/apha.70216","DOIUrl":"10.1111/apha.70216","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Renal sodium reabsorption occurs through both transcellular and paracellular pathways. Tight junction proteins play a key role in mediating paracellular transport. The collecting duct is critical for the fine tuning of sodium balance and is highly responsive to changes in dietary salt intake. This study aimed to determine whether a low-sodium diet modulates paracellular sodium permeability by regulating the expression or localization of claudin-3, a major tight junction protein in the collecting duct.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Wild-type and claudin-3 knockout male mice were fed low (0.01%) or normal (0.18%) sodium diets for 7 days, with or without treatment with spironolactone, a mineralocorticoid receptor antagonist. The expression of tight junction proteins was analyzed by immunoblotting and immunofluorescence. Functional effects of claudin-3 on ion permeability were evaluated in cultured mouse collecting duct principal cells using chamber recordings after claudin-3 overexpression or gene silencing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Low-sodium diet increases claudin-3 expression in mouse kidneys. In cultured cells, aldosterone enhanced claudin-3 abundance and its plasma membrane localization. Claudin-3 overexpression reduced, while its silencing increased paracellular permeability to sodium and chloride. Claudin-3 knockout mice on a low-sodium diet compensated by upregulating epithelial sodium channel subunits, claudin-4, claudin-8, and claudin-10. This adaptive response persisted under mineralocorticoid receptor blockade.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings demonstrate that aldosterone strengthens the paracellular sodium barrier in the collecting duct by inducing claudin-3. In the absence of claudin-3, compensatory regulation of other claudins and sodium transporters preserves sodium homeostasis under low-salt conditions, thus revealing adaptive mechanisms in renal sodium handling.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13047526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147607640","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":"Activity-Dependent Dilation of Mice Brain Capillaries Requires Pericyte Pannexin1 and A1 Adenosine Receptors","authors":"Juan P. Irigoyen,&nbsp;Sandra Mai-Morente,&nbsp;Verónica Abudara","doi":"10.1111/apha.70181","DOIUrl":"10.1111/apha.70181","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Neuronal activity drives increases in cerebral blood flow to match metabolic demands, with capillary dilation critical for blood–brain exchange. However, the molecular mechanisms coupling neuronal activity to capillary diameter adjustments remain unclear. We examined the contribution of pericyte pannexin1 channels to capillary responses during increased neuronal excitability and investigated the underlying signaling pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To induce neuronal excitability, we administered picrotoxin, a GABAA receptor antagonist, to acute hippocampal slices and in vivo, which induces epileptiform activity. Pericyte pannexin1 activity and capillary responses were monitored via dye uptake and capillary diameter measurements in slices from wild-type and pannexin1-deficient mice. Pharmacological blockade of adenosine A1 receptors and exogenous adenosine application were used to identify the signaling pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In vivo picrotoxin administration inhibited pericyte pannexin1 channel activity in the hippocampus. Equivalent suppression was observed in picrotoxin-treated acute hippocampal slices, where neuronal excitability led to pericyte pannexin1 inhibition and capillary dilation. Both responses were abolished by tetrodotoxin and absent in pannexin1-deficient mice, confirming dependence on neuronal activity and pannexin1 expression. Pharmacological blockade of adenosine A1 receptors prevented pannexin1 inhibition and the associated vasodilatory response, whereas exogenous adenosine recapitulated these effects, demonstrating that adenosine signaling is required for neuronal activity–dependent modulation of pericyte pannexin1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We identify a previously uncharacterized adenosine–pannexin1 signaling axis in pericytes linking neuronal excitability to capillary relaxation. This mechanism provides a molecular substrate for activity-dependent capillary regulation and supports a role for pericyte pannexin1 in adenosine-mediated neurovascular responses during states of elevated metabolic demand.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147607657","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":"Supplement: Turkish Society of Physiological Sciences, 50th Turkish Physiology Congress, 12-16 November 2025, Antalya, Türkiye.","authors":"","doi":"10.1111/apha.70209","DOIUrl":"https://doi.org/10.1111/apha.70209","url":null,"abstract":"","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 Suppl 736 ","pages":"e70209"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687109","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":"Supplement: Turkish Society of Physiological Sciences, 50th Turkish Physiology Congress, 12-16 November 2025, Antalya, Türkiye.","authors":"","doi":"10.1111/apha.70210","DOIUrl":"https://doi.org/10.1111/apha.70210","url":null,"abstract":"","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 Suppl 736 ","pages":"e70210"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687077","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}