Experimental Physiology最新文献

{"title":"Pathophysiology of the gut-eye axis in a Sjögren's disease-like dry eye mouse model: An exploratory evaluation of dietary heat-treated Enterococcus faecalis FK-23.","authors":"Kenji Goto, Shigekazu Takemura, Yukiko Minamiyama, Toshikazu Yoshikawa","doi":"10.1113/EP093816","DOIUrl":"10.1113/EP093816","url":null,"abstract":"<p><p>Sjögren's disease is an autoimmune disease characterized by severe dry eye, but its pathophysiology remains unclear. Non-obese diabetic (NOD) mice develop Sjögren's disease-like dry eye prior to the onset of diabetes. Although intestinal immune abnormalities precede diabetes in NOD mice, their relationship to dry eye remains poorly understood. This study investigated pathological changes in the lacrimal gland (LG) and small intestine of NOD mice and evaluated the potential effects of dietary heat-treated Enterococcus faecalis FK-23 (FK-23). Four-week-old male NOD mice were fed either a standard diet or a diet containing 3% FK-23 for 2 weeks. BALB/c mice served as controls. Tear secretion was measured following pilocarpine administration. LG and small intestine tissues were analysed histologically, and intestinal lymphocytes were evaluated by flow cytometry and next-generation sequencing. At 4 weeks of age, NOD mice exhibited normal tear secretion and no apparent LG inflammation but showed reduced small intestinal crypt granules and decreased proportions of ILC3 and T helper 17 cells. At 6 weeks, NOD mice demonstrated reduced tear secretion, inflammatory cell infiltration in the LG, and loss of crypt granules and goblet cells in the small intestine. Dietary FK-23 administration showed trends towards attenuating tear secretion decline, LG inflammation and intestinal pathological changes. Development of LG inflammation and dry eye in NOD mice was associated with intestinal immune and epithelial abnormalities. These findings suggest potential involvement of the gut-eye axis in Sjögren's disease-like dry eye pathogenesis and indicate that modulation of intestinal homeostasis might represent a therapeutic strategy.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"4507-4524"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13458304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiological and autonomic responses to intermittent low-lung-volume apnoea and pain sensitivity: A randomized controlled pilot trial.","authors":"Cristian Mendoza-Arranz, Francisco De Asís-Fernández, Guillermo Miravet-Mingo, José Vicente León-Hernández, José Fierro-Marrero, Álvaro Reina-Varona","doi":"10.1113/EP093960","DOIUrl":"10.1113/EP093960","url":null,"abstract":"<p><p>Intermittent apnoeas may induce hypoalgesia; however, the effects of low-lung-volume static apnoea have not been investigated. Eighty healthy participants were randomized to an apnoea group (AG) or a control group (CG). The AG performed a 6-min protocol of intermittent static apnoea at low lung volume (passive exhalation), whereas the CG breathed normally in the supine position. Pressure pain thresholds (PPTs) were assessed at the thumb, tibialis anterior and C7, together with heart rate (HR), oxygen saturation ( <math><msub><mi>S</mi> <mrow><mi>p</mi> <msub><mi>O</mi> <mn>2</mn></msub> </mrow> </msub> </math> ), and systolic and diastolic blood pressure (SBP and DBP). Open-ended questions explored sensations, emotions and adverse effects. ANCOVA (baseline pressure pain threshold) revealed no significant between-group differences in PPT at thumb (mean difference [MD] = -0.209 kg/cm²; 95% CI: -0.584, 0.158; P = 0.268), tibialis (MD = 0.014 kg/cm²; 95% CI: -0.341, 0.354; P = 0.939), or C7 (MD = -0.276 kg/cm²; 95% CI: -0.669, 0.102; P = 0.169). Intrasession analyses showed higher values in the AG for <math><msub><mi>S</mi> <mrow><mi>p</mi> <msub><mi>O</mi> <mn>2</mn></msub> </mrow> </msub> </math> (MD = 0.598%, P = 0.009), percentage maximum heart rate (MD = 4.344%, P < 0.0001), SBP (MD = 15.344 mmHg, P < 0.0001) and DBP (MD = 14.273 mmHg, P < 0.0001). The AG reported more distress-related sensations and emotions, whereas the CG described more comfort-related experiences. Adverse effects were mild. A 6-min intermittent low-lung-volume static apnoea did not induce hypoalgesia despite autonomic and cardiovascular activation and was well tolerated. These findings suggest respiratory-induced autonomic stress may be insufficient to modulate nociceptive processing, highlighting the importance of physiological conditions under which breath-hold interventions may influence pain. Trial registration: This study was prospectively registered on 27 November 2023, at ClinicalTrials.gov (Identifier: NCT06158256).</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"4928-4941"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13544601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term endurance running training and testosterone daily variation in ageing men; a comparative cross-sectional study.","authors":"Barbora Bartko, Ľudmila Oreská, Gabriel Buzgó, Genc Berisha, Valentína Zemaníková, Monika Okuliarová, Michal Zeman, Milan Sedliak","doi":"10.1113/EP093482","DOIUrl":"10.1113/EP093482","url":null,"abstract":"<p><p>The aim of this study was to assess the relationship between long-term endurance running training and daily variation in testosterone, which is known to diminish during ageing, in a comparative, cross-sectional study. We recruited 45 male participants into four groups [young athletes (YA), young sedentary (YS), master athletes (MA) and elderly sedentary (ES)] and performed anthropometry, strength and ergometry tests. Morning (AM) and afternoon (PM) venous blood samples were collected to evaluate testosterone daily variation, sex hormone binding globulin (SHBG), cortisol and estradiol, and we calculated free testosterone, bioavailable testosterone and the free androgen index. Two-way and three-way ANOVAs followed by Bonferroni's multiple comparisons tests were performed. The free testosterone and free androgen index showed a significant PM decrease in the MA group (P = 0.0009 and 0.0021, respectively), comparable to YA and YS; however, in the ES group there was no difference between AM and PM values (both P > 0.9999). SHBG levels were significantly increased by both the age (P = 0.0001) and activity (P = 0.0016) factors, leading to a significant decrease in free testosterone, bioavailable testosterone and free androgen index. In the peak power output parameters of ergometry, expressed in both absolute and relative values, MA achieved values comparable to YS, significantly higher than ES (P = 0.0020 and P < 0.0001, respectively) and lower than YA (P < 0.0001). In conclusion, long-term endurance running training in elderly men might be associated with the presence of daily variation in free testosterone and higher performance levels in comparison to sedentary counterparts, but it might contribute to age-related changes in SHBG and related testosterone fraction levels.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"4620-4635"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13576003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148966886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Feedback from group III/IV afferents in skeletal muscle slows heart rate acceleration when transitioning from rest to low-intensity exercise in males","authors":"Shane Burgess,&nbsp;Simranjit K Sidhu,&nbsp;Samuel Chalmers,&nbsp;Markus Amann,&nbsp;Jonathan D Buckley","doi":"10.1113/EP093776","DOIUrl":"10.1113/EP093776","url":null,"abstract":"<p>Group III/IV skeletal muscle afferents respond to intramuscular mechanical and metabolic stimuli and are more active in fatigued muscle. These afferents project onto the brainstem and motor cortex and modulate cardiovascular and motor responses during exercise. The maximal rate of heart rate (HR) increase (rHRI), a marker of HR acceleration during the rest-to-exercise transition, is linearly related to exercise performance across various training and fatigue states, being faster with better exercise performance and vice versa. This study evaluated the effect of feedback from group III/IV afferents on rHRI in non-fatigued muscle. HR data were collected in eight recreationally active male participants (24 ± 1 years) during the transition from rest to 3 min of cycling at 100 W under control (CON) conditions and following lumbar intrathecal fentanyl (FENT) infusion to impair feedback from group III/IV afferents of the leg. rHRI was defined as the maximal first-derivative value of a logistic curve fitted to the HR data. Pre-exercise HR was similar in CON and FENT (CON 91.7 ± 16.7 bpm, FENT 99.8 ± 15.5 bpm, <i>P</i> = 0.250). HR increased more with exercise during CON than FENT (B = 10.01, 95% CI 5.33 to 14.70, <i>P </i>&lt; 0.001) but rHRI was faster during FENT (B = 1.52, 95% CI 0.24 to 2.80, <i>P</i> = 0.020). In non-fatigued muscle, feedback from group III/IV afferents slowed rHRI. Increased feedback when muscle is fatigued may slow rHRI further which may explain the relationship between rHRI and exercise performance seen in previous studies, but further studies on fatigued muscle are required to confirm this.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":"111 10","pages":"4344-4350"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The importance of cross-talk in research and the body: An early career researcher perspective","authors":"Lucy J. Ryan,&nbsp;Jamie A. Elliott,&nbsp;Robert Little,&nbsp;Mhairi A. Paul","doi":"10.1113/EP093955","DOIUrl":"10.1113/EP093955","url":null,"abstract":"&lt;p&gt;Interdisciplinary research is increasingly important for advancing science. Early-career researchers (ECRs) play a central role in driving this progress and bridging gaps between fields. Inspired by a recent ECR-focused multidisciplinary symposium, this editorial reflects on the importance of ECR engagement across disciplines and highlights examples of current interdisciplinary research.&lt;/p&gt;&lt;p&gt;Recent technological advancements have accelerated biological discovery and yielded unprecedented amounts of data (D'Argenio, &lt;span&gt;2018&lt;/span&gt;; Vitorino, &lt;span&gt;2024&lt;/span&gt;). However, this scientific progress has revealed ever-growing complexity and elicited endless new questions. In recent decades, there has been an exponential growth in scientific publication (Bornmann et al., &lt;span&gt;2021&lt;/span&gt;; Pautasso, &lt;span&gt;2012&lt;/span&gt;) with modern scientific reports containing increasingly large datasets, diverse methodologies and requiring longer times to publish (Vale, &lt;span&gt;2015&lt;/span&gt;). While scientific discovery historically centred on the esteem of individual genius, the value of teamwork is undeniable in modern science. Evidence of the shift towards collaborative science is reflected in the increase in co-authorship on publications (Vale, &lt;span&gt;2015&lt;/span&gt;; Zhou and Nunes Amaral, &lt;span&gt;2025&lt;/span&gt;). Indeed, there has been a sharp rise in the number of publications with 10 or more authors from the 1960s onwards (Zhou and Nunes Amaral, &lt;span&gt;2025&lt;/span&gt;), and leading journals such as &lt;i&gt;Cell&lt;/i&gt; and &lt;i&gt;Nature&lt;/i&gt; show a two- to four-fold increase in authors per paper since the 1980s (Vale, &lt;span&gt;2015&lt;/span&gt;). Furthermore, publications authored by a team of researchers tend to be more highly cited than publications by solo authors, suggesting a higher scientific impact of collaborative studies (Wuchty et al., &lt;span&gt;2007&lt;/span&gt;).&lt;/p&gt;&lt;p&gt;Alongside the rise of collaborative science, interdisciplinary research has gained prominence. This is evidenced by research publications increasingly citing studies outside of their own discipline (Van Noorden, &lt;span&gt;2015&lt;/span&gt;) and high-impact journals increasingly publishing interdisciplinary articles (Zhou and Nunes Amaral, &lt;span&gt;2025&lt;/span&gt;). Indeed, team diversity is associated with creativity and the emergence of new knowledge (Berliant and Fujita, &lt;span&gt;2008&lt;/span&gt;; Guimera et al., &lt;span&gt;2005&lt;/span&gt;; Pennington, &lt;span&gt;2016&lt;/span&gt;). Beyond improving the quality of science, interdisciplinary research advances professional development by challenging researchers to refine their ability to communicate concepts, become aware of the boundaries of their own discipline, stimulates learning, broadens perspectives and promotes innovative thinking (Mahringer et al., &lt;span&gt;2023&lt;/span&gt;). Moreover, interdisciplinary biomedical studies are more likely to be cited by patents, suggesting higher translational potential (Ke, &lt;span&gt;2023&lt;/span&gt;).&lt;/p&gt;&lt;p&gt;ECRs – comprising PhD students, post-doctoral researchers and emerging principal investigat","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":"111 10","pages":"4255-4261"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13456519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RETRACTED: Surgery in space: The ultimate frontier.","authors":"Mohamad Bashir, Ali Murtada, Matti Jubouri, Adam Bashir, Ian Williams, Damian Bailey","doi":"10.1113/EP092765","DOIUrl":"10.1113/EP092765","url":null,"abstract":"","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"4943-4948"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Haemodynamic effects of selective venoconstriction with centhaquine in spontaneously breathing patients with mixed hypovolaemic-vasodilatory shock","authors":"Athanasios Chalkias,&nbsp;Aman Khanna,&nbsp;Krish Vaidya,&nbsp;Dharmesh Shah,&nbsp;Anil Gulati","doi":"10.1113/EP093743","DOIUrl":"10.1113/EP093743","url":null,"abstract":"<p>Circulatory shock remains difficult to manage because fluid resuscitation and catecholamines may exacerbate vascular dysfunction and tissue hypoperfusion. This prospective physiological analysis, embedded within a multicentre phase IV study, examined whether selectively targeting the venous circulation with centhaquine improves circulatory dynamics in spontaneously breathing patients with mixed hypovolaemic–vasodilatory shock (MHVS). Fifteen spontaneously breathing adults with MHVS received centhaquine (0.01 mg kg⁻¹) in addition to standard care. Over 300 min, mean circulatory filling pressure analogue increased from 6.03 ± 0.22 to 7.28 ± 0.21 mmHg and driving pressure for venous return from 5.88 ± 0.22 to 7.16 ± 0.21 mmHg (adjusted <i>P </i>&lt; 0.001 for both), while estimated central venous pressure remained near atmospheric pressure and resistance to venous return remained unchanged. Cardiac output increased from 5.62 ± 0.22 to 6.80 ± 0.24 L min⁻¹ and mean arterial pressure from 56.8 ± 1.5 to 69.8 ± 2.0 mmHg (adjusted <i>P </i>&lt; 0.001 for both). Effective arterial elastance and systemic vascular resistance did not significantly change over time. Patients received 677 ± 79 mL of crystalloids during the study period, and no drug-related adverse events were observed. The findings of this preliminary physiological study suggest that selective venoconstriction may augment venous return and systemic haemodynamics in spontaneously breathing patients with MHVS without evidence of major adverse haemodynamic effects.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":"111 10","pages":"4421-4434"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma β-hydroxybutyrate concentrations in young adult females after a high-fat meal under normoxaemia, intermittent hypoxaemia and continuous hypoxaemia: An exploratory analysis","authors":"Nicholas Goulet,&nbsp;Alexanne Larocque,&nbsp;Caroline Marcoux,&nbsp;Vincent Bourgon,&nbsp;Jean-François Mauger,&nbsp;Ruwan Amaratunga,&nbsp;Pascal Imbeault","doi":"10.1113/EP093829","DOIUrl":"10.1113/EP093829","url":null,"abstract":"<p>Hypoxaemia occurs in intermittent forms, such as obstructive sleep apnoea, and in continuous forms, such as at high altitude, and is increasingly recognized as a modulator of cardiometabolic risk. Although hypoxaemia alters postprandial glucose and lipid metabolism, its effects on ketone bodies remain unclear. Using a randomized crossover design, we examined whether 6 h of normoxaemia or intermittent hypoxaemia (15 hypoxaemic cycles/h targeting ∼85% peripheral oxyhaemoglobin saturation with 100% medical-grade nitrogen) alters plasma β-hydroxybutyrate (BHB) concentrations in 12 young adult females (mean [SD]: 21 [3] years) following a high-fat meal (33% of estimated daily energy requirements; 59% of energy from fat). In a follow-up session, a subset (<i>n</i> = 8) completed 6 h of continuous hypoxaemia (fraction of inspired oxygen ∼12.0% in a normobaric chamber). Postprandial data were analysed using baseline-adjusted linear mixed-effects models, with Bonferroni post hoc tests. A time × condition interaction (<i>P</i> = 0.010) indicated that BHB concentrations at 360 min were higher during continuous hypoxaemia (0.247 mmol/L; 95% CI: 0.218–0.275) than normoxaemia (0.176 mmol/L; 95% CI: 0.153–0.200; <i>P</i>_Bonferroni = 0.029) and intermittent hypoxaemia (0.163 mmol/L; 95% CI: 0.139–0.186; <i>P</i>_Bonferroni = 0.002), representing increases of 13.0% and 14.2% in estimated marginal means, respectively. This response was accompanied by higher postprandial plasma glucose and triglyceride concentrations during continuous hypoxaemia than during normoxaemia and intermittent hypoxaemia (<i>P</i>_Bonferroni ≤ 0.002), despite similar plasma insulin and non-esterified fatty acid responses across conditions (<i>P</i> ≥ 0.081). These findings indicate that continuous hypoxaemia increases late postprandial plasma BHB concentrations in young adult females.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":"111 10","pages":"4303-4314"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13400008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148583758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute lower leg transcutaneous electrical nerve stimulation increases leg blood flow and exercise capacity in patients with peripheral arterial disease","authors":"Thomas K. Pellinger,&nbsp;Catherine B. Neighbors,&nbsp;Joshua C. Hefta,&nbsp;Patrick H. Luo,&nbsp;Carl B. Suarez,&nbsp;Erotokritos T. Varlas,&nbsp;Grant H. Simmons,&nbsp;Brett J. Wong","doi":"10.1113/EP093618","DOIUrl":"10.1113/EP093618","url":null,"abstract":"<p>We tested the hypothesis that two different durations of lower leg transcutaneous electrical nerve stimulation (TENS) increase post-TENS popliteal artery blood flow (PABF), popliteal vascular conductance (PVC), and 6-min walk distance (6MWD) in patients with peripheral artery disease (PAD). Seven subjects (5 male, 2 female) with PAD (67.9 ± 7.4 years; claudication: ankle-brachial index (ABI) &lt;0.90) participated in three randomized treatment sessions: control or bilateral TENS (3.0 Hz burst mode, 250 µs) for either 15 or 45 min. PABF (Doppler ultrasound) was measured before and after treatment. 6MWD and time/distance to claudication onset were measured 25 min post-treatment during each session. PABF, PVC and 6MWD increased after both 15 and 45 min of TENS (<i>P</i> &lt; 0.05, post-TENS vs. pre-TENS baseline/control). Our preliminary results suggest that as little as 15 min of lower leg TENS increases leg blood flow and exercise capacity in individuals with PAD.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":"111 10","pages":"4296-4302"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148548347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FGF23 promotes atrial fibrillation susceptibility through ETV1-dependent sodium channel regulation and calcium handling abnormalities","authors":"Qiaoting Yu,&nbsp;Linwen Zeng,&nbsp;Zhijie Chen,&nbsp;Zhuhui Lin,&nbsp;Congying Wang,&nbsp;Lan Wang,&nbsp;Huixian Fu,&nbsp;Jiancheng Zhang","doi":"10.1113/EP093891","DOIUrl":"10.1113/EP093891","url":null,"abstract":"<p>Fibroblast growth factor 23 (FGF23) is closely associated with atrial fibrillation (AF), yet whether it modulates sodium and calcium currents in atrial myocytes remains unclear. ETV1, a key transcription factor regulating atrial electrical conduction, might also be involved in FGF23-mediated AF. In this study, FGF23 intervention models were established via tail vein injection in mice and direct administration in vitro. ETV1 knockdown and overexpression were achieved in vitro using lentiviral vectors, and ETV1 knockout mice were generated. Patch-clamp electrophysiology, calcium imaging and western blotting were performed to assess electrophysiological properties and AF susceptibility. Functionally, FGF23 increased both peak and residual sodium current measured 3 ms after peak activation, while also enhancing L-type calcium current, prolonging action potential duration and promoting early and delayed after-depolarizations. Consistent with these electrophysiological changes, Nav1.5 and RyR2 expression levels were upregulated, accompanied by increased intracellular calcium transients, thereby leading to increased AF susceptibility. In mechanistic analyses, ETV1 knockdown attenuated FGF23-induced increases in sodium current and action potential parameters but did not reduce AF susceptibility, whereas ETV1 knockout increased AF inducibility. These findings suggest that FGF23 promotes AF by inducing coordinated electrical and calcium handling abnormalities that facilitate triggered activity, while ETV1 contributes to FGF23-induced sodium channel regulation.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":"111 10","pages":"4435-4456"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13502996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}