Acta Physiologica最新文献

{"title":"Comparison of Phasic Store-Operated Calcium Entry in Rat Slow- and Fast-Twitch Muscle Fibers","authors":"Elena Lilliu,&nbsp;Rocky Choi,&nbsp;Karlheinz Hilber,&nbsp;Bradley Launikonis,&nbsp;Xaver Koenig","doi":"10.1111/apha.70059","DOIUrl":"https://doi.org/10.1111/apha.70059","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This study investigates the activation and regulation of phasic store-operated calcium entry (pSOCE) in fast- and slow-twitch skeletal muscle fibers. Specifically, we aimed to enhance the sensitivity of pSOCE detection in slow-twitch fibers by optimizing ionic conditions and to compare the physiological relevance of pSOCE between fiber types.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We employed mechanically skinned fast-twitch extensor digitorum longus (EDL) muscle fibers loaded with spectrally distinct Ca²⁺-sensitive dyes to simultaneously measure action potential-induced sarcoplasmic reticulum Ca²⁺ release and t-tubular system Ca²⁺ dynamics with millisecond resolution. Experimental conditions were optimized by reducing cytosolic Mg²⁺ and EGTA buffering to enhance Ca²⁺ release in slow-twitch soleus fibers. Confocal microscopy was used to track t-tubular system Ca²⁺ depletion and reuptake during electric field stimulation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Skinned soleus fibers exhibited ~8-fold lower Ca²⁺ release per action potential compared to EDL fibers, yet pSOCE amplitudes were comparable. Reducing Mg²⁺ and EGTA levels increased Ca²⁺ release and left pSOCE kinetics in EDL fibers unaltered, but enabled pSOCE measurements in soleus fibers. While pSOCE in EDL fibers followed a linear dependence on the ambient Ca²⁺ concentration in the t-tubular system, such a relationship was violated in soleus fibers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings reveal a novel, fiber-type-specific difference in pSOCE regulation. When compared to EDL fibers, soleus fibers exhibited a higher sensitivity to SOCE activation despite releasing less Ca²⁺ from the sarcoplasmic reticulum upon an action potential. These differences may allow soleus fibers to sustain Ca²⁺ homeostasis more effectively, be more resilient against disruptions in Ca²⁺ handling, and entail protection against disease states.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70059","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085502","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":"Correction to “Neuronal Activity Modulates the Expression of Secretagogin, a Ca2+ Sensor Protein, During Mammalian Forebrain Development”","authors":"","doi":"10.1111/apha.70055","DOIUrl":"https://doi.org/10.1111/apha.70055","url":null,"abstract":"<p>Hanics J, Tretiakov EO, Romanov RA, et al. Neuronal activity modulates the expression of secretagogin, a Ca²⁺ sensor protein, during mammalian forebrain development. <i>Acta Physiol</i>. 2025;241:e70031. https://doi.org/10.1111/apha.70031.</p><p>In the originally published version of record, the funding statement was missing: Open access funding provided by Medizinische Universität Wien/KEMÖ.</p><p>The online version of this article has been corrected accordingly.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70055","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944791","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":"Carbamylation versus Carboxylation—A Clash Culminating in Vascular Calcification?","authors":"Jakob Voelkl,&nbsp;Mirjam Schuchardt","doi":"10.1111/apha.70054","DOIUrl":"https://doi.org/10.1111/apha.70054","url":null,"abstract":"&lt;p&gt;In their recent work in &lt;i&gt;Acta Physiologica&lt;/i&gt;, Kaesler et al. identify a novel mechanistic link between the uremic environment in chronic kidney disease (CKD) and vascular calcification [&lt;span&gt;1&lt;/span&gt;]. Medial vascular calcification (VC) is an inappropriate deposition of calcium-phosphate, mostly as hydroxyapatite, in the medial layer of the arteries [&lt;span&gt;2&lt;/span&gt;]. This VC increases with aging and is strongly accelerated by CKD [&lt;span&gt;2&lt;/span&gt;]. The intricate and multifaceted pathogenesis of VC is tightly linked to calcium–phosphate imbalance. When calcium and phosphate concentrations exceed their solubilities in the plasma, spontaneous complexation and formation of extraosseous minerals could occur that is physiologically balanced by a mineral buffering system [&lt;span&gt;3&lt;/span&gt;]. In CKD patients, bone demineralization and hyperphosphatemia strain the physiological mineral buffering system [&lt;span&gt;2&lt;/span&gt;]. Thereby, an increased formation of calcium–phosphate particles can occur, which in turn can induce pro-inflammatory cascades. The stimulation of this pro-inflammatory effect is further exacerbated by the accumulation of uremic toxins in the plasma of CKD patients [&lt;span&gt;4&lt;/span&gt;]. Vascular smooth muscle cells (VSMC) are particularly susceptible to calcium–phosphate particle stress and respond with phenotypic changes, including activation of inflammatory pathways, release of pro-calcific transmitters and extracellular vesicles as well as remodeling of the extracellular matrix. All these changes favor a local pro-calcific microenvironment [&lt;span&gt;2&lt;/span&gt;]. From this perspective, rectifying a deranged mineral buffering system in CKD holds great potential to prevent VC and reduce cardiovascular mortality.&lt;/p&gt;&lt;p&gt;Several factors of the mineral buffering system, such as pyrophosphate and fetuin-A, have been linked to an anticalcific function [&lt;span&gt;2, 3&lt;/span&gt;]. Additionally, a decisive role has been attributed to vitamin-K-dependent GLA proteins [&lt;span&gt;5&lt;/span&gt;]. Contrary to osteocalcin (bone GLA protein), matrix GLA protein (MGP) is a potent extraosseous calcification inhibitor. MGP is a ~12-kDa protein that was originally identified from bone matrix but is also highly expressed in soft tissues. Its critical role was identified in MPG-deficient mice that die from rupture of their calcified arteries before they reach an age of 2 months. Interestingly, the anticalcific effects of MGP might involve several mechanisms [&lt;span&gt;5&lt;/span&gt;]. MGP directly adsorbs hydroxyapatite crystals and is associated with inhibition of crystal growth but may also inhibit bone morphogenic protein 2, an important activator of pro-calcific effects in VSMCs [&lt;span&gt;5&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;The function of MGP is regulated by posttranslational modifications, such as phosphorylation and carboxylation. Besides serine phosphorylation, the gamma-carboxylation of glutamate residues by gamma-glutamyl carboxylase (GGCX) and vitamin K as co-factor is important for the anti-calcific fun","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70054","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930322","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":"Voltage-Gated Ca2+ Channels in Prefrontal Parvalbumin Neurons Are Essential for Stress-Induced Depression","authors":"Katrina Lin,&nbsp;Laurence Coutellier","doi":"10.1111/apha.70053","DOIUrl":"https://doi.org/10.1111/apha.70053","url":null,"abstract":"&lt;p&gt;Stress is a risk factor for neuropsychiatric disorders, including depression. While acute stress responses are typically protective and adaptive, prolonged or chronic stress can lead to lasting alterations in brain function that contribute to maladaptive behaviors. Among the brain regions affected by chronic stress, the prefrontal cortex (PFC) stands out due to its critical role in regulating affect, cognition, and top-down control of limbic circuits. Studies with rodent models show that chronic stress induces dendritic retraction, synaptic loss, and disruptions in excitatory/inhibitory (E/I) balance within the PFC [&lt;span&gt;1-3&lt;/span&gt;]. These findings parallel neuroimaging studies in humans showing reduced PFC volume and hypoactivity in individuals with stress-related disorders, including major depressive disorder and post-traumatic stress disorder [&lt;span&gt;4, 5&lt;/span&gt;]. While disruption of parvalbumin-expressing (PV+) inhibitory GABAergic neurons has been found to drive some of the effects of chronic stress on anxiety- and depressive-like behaviors in rodents [&lt;span&gt;2, 6, 7&lt;/span&gt;], the molecular mechanisms linking stress-induced GABAergic dysfunction to long-term behavioral consequences have yet to be fully understood. In a recent issue of &lt;i&gt;Acta Physiologica&lt;/i&gt;, Yabuki et al. [&lt;span&gt;8&lt;/span&gt;] propose a novel understanding of the molecular mechanisms underlying chronic-stress induced depression using a rodent model.&lt;/p&gt;&lt;p&gt;The authors investigate the role of Cav3.1 T-type calcium channels, located on PV+ neurons in the medial PFC (mPFC), in stress-induced behavioral changes. Using Cav3.1 knockout mice, they demonstrate that deletion of the Cav3.1 channel prevents the development of depressive-like behaviors typically induced by acute stress paradigms such as the forced swim test (FST) and tail suspension test (TST). While these assays are conventionally used to assess acute stress responses, they are leveraged here to measure chronic stress-induced depressive-like behaviors. Stress-induced immobility was abolished in Cav3.1-deficient mice, indicating that Cav3.1 channels are necessary for inducing such depressive-like behavioral phenotypes.&lt;/p&gt;&lt;p&gt;To further probe the underlying neural mechanisms, the authors employed transcriptomic profiling of the mPFC, which revealed that chronic stress alters the expression of genes involved in E/I balance and synaptic signaling in wild-type mice, but not Cav3.1 knockout mice. These changes were particularly pronounced in genes associated with GABAergic transmission, implicating Cav3.1 in modulating the effects of chronic stress on inhibitory circuits in the mPFC.&lt;/p&gt;&lt;p&gt;Electrophysiological recordings demonstrated that chronic stress enhances the excitability of PV+ GABAergic neurons in the mPFC of wild-type mice, but not in Cav3.1-deficient mice, providing a mechanistic link between Cav3.1 channel activity, interneuron excitability, and behavioral output. Optogenetic activation of PV+ neurons in the mPFC wa","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70053","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926164","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":"SorCS2 Is Important for Astrocytic Function in Neurovascular Signaling","authors":"Christian Staehr,&nbsp;Hande Login,&nbsp;Elizaveta V. Melnikova,&nbsp;Magdalena Bakun,&nbsp;Ewelina Ziemlinska,&nbsp;Lilian Kisiswa,&nbsp;Simin Berenji Ardestani,&nbsp;Stella Solveig Nolte,&nbsp;Hans Christian Beck,&nbsp;Line Mathilde Brostrup Hansen,&nbsp;Dmitry Postnov,&nbsp;Alexei Verkhratsky,&nbsp;Anna R. Malik,&nbsp;Anders Nykjaer,&nbsp;Vladimir V. Matchkov","doi":"10.1111/apha.70052","DOIUrl":"https://doi.org/10.1111/apha.70052","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The receptor SorCS2 is involved in the trafficking of membrane receptors and transporters. It has been implicated in brain disorders and has previously been reported to be indispensable for ionotropic glutamatergic neurotransmission in the hippocampus.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>We aimed to study the role of SorCS2 in the control of astrocyte-neuron communication, critical for neurovascular coupling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Brain slices from P8 and 2-month-old wild-type and SorCS2 knockout (<i>Sorcs2</i>^{<i>−/−</i>}) mice were immunostained for SorCS2, GFAP, AQP4, IB4, and CD31. Neurovascular coupling was assessed in vivo using laser speckle contrast imaging and ex vivo in live brain slices loaded with calcium-sensitive dye. Bulk and cell surface fraction proteomics was analyzed on freshly isolated and cultured astrocytes, respectively, and validated with Western blot and qPCR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SorCS2 was strongly expressed in astrocytes, primarily in their endfeet, of P8 mice; however, it was sparsely represented in 2-month-old mice. <i>Sorcs2</i>^{<i>−/−</i>} mice demonstrated reduced neurovascular coupling associated with a reduced astrocytic calcium response to neuronal excitation. No differences in vascularization or endothelium-dependent relaxation ex vivo between the 2-month-old groups were observed. Proteomics suggested changes in glutamatergic signaling and suppressed calcium signaling in <i>Sorcs2</i>^{<i>−/−</i>} brains from both P8 and 2-month-old mice. The increased abundance of glutamate metabotropic receptor 3 in <i>Sorcs2</i>^{<i>−/−</i>} astrocytes was validated by PCR and Western blot. In cultured <i>Sorcs2</i>^{<i>−/−</i>} astrocytes, AQP4 abundance was increased in the bulk lysate but reduced in the cell surface fraction, suggesting impaired trafficking.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The results suggest that SorCS2 expression is important for the development of neurovascular coupling, at least in part by modulating glutamatergic and calcium signaling in astrocytes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919656","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":"Sodium-Coupled Monocarboxylate Absorption in the Airway Epithelium Is Facilitated by the SLC5A8 Co-Transporter","authors":"Anita Guequen,&nbsp;Bárbara Tapia-Balladares,&nbsp;Tábata Apablaza,&nbsp;Daniela Guidone,&nbsp;Nátali Cárcamo-Lemus,&nbsp;Sandra Villanueva,&nbsp;Pamela Y. Sandoval,&nbsp;Luis J. V. Galietta,&nbsp;Carlos A. Flores","doi":"10.1111/apha.70051","DOIUrl":"https://doi.org/10.1111/apha.70051","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Amino acids, sugars, short-chain fatty acids (SCFA), vitamins, and other small molecules compose the extracellular metabolome on the airway lumen surface, but how the airway epithelium deals with these molecules has not been deeply studied. Due to the broad spectrum of metabolites transported by SLC5A8 and SLC5A12, we aim to determine if they are functionally expressed and participate in the absorption of Na⁺, short-chain fatty acids, and monocarboxylates in mouse and human airway epithelium.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Tracheas isolated from male or female mice and human bronchial epithelial cells (HBECs) were used for electrophysiological studies in the Ussing chamber and to detect members of the SLC16 family by RT-PCR and bulk RNAseq. Additionally, cell lines expressing the human and murine SLC5A8 transporter were employed for uptake studies using a fluorescent lactate probe.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We showed for the first time that human and murine airway epithelium express a functional SLC5A8 transporter, facilitating the absorption of glucose metabolites and SCFAs. The Na⁺-coupled monocarboxylate transport was not additive with ENaC-mediated Na⁺ absorption in mouse trachea. We observed that valproate acts as an inhibitor of the murine but not of the human SLC5A8 transporter.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results demonstrate that several metabolites derived from bacterial and cellular metabolism can be transported from the airway lumen into the epithelial cells, participating in a homeostatic relation of the tissue with its environment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143908914","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":"Cerebrospinal Fluid Enters Peripheral Organs by Spinal Nerves Supporting Brain–Body Volume Transmission","authors":"Baoman Li,&nbsp;Maosheng Xia,&nbsp;Tibor Harkany,&nbsp;Alexei Verkhratsky","doi":"10.1111/apha.70048","DOIUrl":"https://doi.org/10.1111/apha.70048","url":null,"abstract":"&lt;p&gt;The cerebrospinal fluid (CSF) provides many vital functions to the central nervous system (CNS). The CSF irrigates the CNS from within (through the ventricular system and the central canal of the spinal cord) and from without (through the sub-arachnoid space of the cranium and spine). As the brain and spinal cord therefore float within the CSF, the CNS is hydromechanically protected by the CSF, and the Archimedean principle of buoyancy means that the mass of the suspended brain is reduced from ~1.5 kg to mere 50 g. The CSF also acts as a hydraulic shock absorber that prevents the brain from hitting the skull and thus provides us the freedom of movement and acceleration. Simply put, the hydraulic shock absorption is the reason none of us incur debilitating concussions each time we take a step! Moreover, the CSF nourishes the CNS by providing a highway for nutrients and signaling molecules that are transported from the blood in the cerebral circulation to the CSF, and then to the interstitial fluid within the extracellular space of the nervous tissue. The CSF also provides haulage to a variety of waste products. In addition to these housekeeping functions, the CSF is a medium for long-range signaling within the CNS and between the CNS and the body, by carrying hormones, neurotransmitters, neuromodulators, signal-competent molecules, or extracellular vesicles over long distances.&lt;/p&gt;&lt;p&gt;The CSF production and flow are intimately associated with the ventricular system of the brain, the central canal of the spinal cord, and the sub-arachnoid space. The mammalian brain contains four ventricles: two lateral, localized quasi-symmetrically in each of the hemispheres, the third ventricle at the midline of the diencephalon, as well as the fourth ventricle of the hindbrain. The lateral ventricles are connected to the third ventricle through the foramen of Monro, while the third and fourth ventricles are linked with the cerebral aqueduct of Sylvius. The fourth ventricle is continuous with the central canal of the spinal cord and connected to the subarachnoid space through exits at the foraminae Magendie and Luschka [&lt;span&gt;1&lt;/span&gt;]. The CSF is produced mainly by four choroid plexi (one per ventricle) although extrachoroid sites may also contribute [&lt;span&gt;2&lt;/span&gt;]. Choroid plexi are lined with a monolayer of specialized “choroid” epithelium. This name is, however, incorrect: cells building the choroid plexi are &lt;i&gt;bona fide&lt;/i&gt; ependymoglia: committed precursors of choroid cells are scions of a subpopulation of neuroepithelial precursors that emerge around embryonic Day 11 in mice, prior to the start of neurogenesis [&lt;span&gt;3&lt;/span&gt;]. The cuboid choroid ependymocytes have several cilia and form a CSF-blood barrier reinforced by intercellular junctional complexes made of tight junctions, adherens junctions, and desmosomes [&lt;span&gt;4&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;The production of the CSF is supported by multiple plasmalemmal transporters that are selectively recruited at apic","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70048","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905116","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":"A Physiological Model of Cardiac Fibrosis: Changes to Maintain Function in the Cold","authors":"Todd E. Gillis","doi":"10.1111/apha.70050","DOIUrl":"https://doi.org/10.1111/apha.70050","url":null,"abstract":"&lt;p&gt;Cardiac fibrosis occurs in response to several pathologies including myocardial infarction (MI) and hypertension. The increased deposition of connective tissue translates into an increase in passive stiffness, as well as impairment of electrical activation of the tissue. The result is a loss of systolic and diastolic function. Subsequent compensatory responses can lead to greater loss of function, including the development of dilated cardiomyopathy and eventual heart failure. In these disease models, fibrosis is irreversible and there is a dire lack of interventions to restore function. However, in the recent &lt;i&gt;Acta Physiologica&lt;/i&gt; publication, Keen et al. [&lt;span&gt;1&lt;/span&gt;] characterize a fibrotic response in freshwater turtles that occurs under physiological conditions that help maintain cardiac function at low temperatures. In fact, cardiac fibrosis can be induced in several ectothermic (cold-blooded) animals, including rainbow trout and freshwater turtles, in response to a decrease in physiological temperature [&lt;span&gt;2, 3&lt;/span&gt;]. In addition, warm acclimation causes a decrease in the collagen content of the trout heart [&lt;span&gt;2&lt;/span&gt;]. These changes are due, at least in part, to altered expression of gene transcripts for collagen monomers as well as proteins involved in regulating collagen turnover [&lt;span&gt;4&lt;/span&gt;]. This includes matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs) (Figure 1) [&lt;span&gt;4&lt;/span&gt;]. Together, these studies suggest that the collagen content in a vertebrate heart is plastic, and that fibrosis can be reversible.&lt;/p&gt;&lt;p&gt;Freshwater turtles overwinter in ponds where temperatures are at least 10°C–15°C colder than in summer and there is limited oxygen [&lt;span&gt;5&lt;/span&gt;]. With a 15°C cold acclimation, the heart rate of red-eared slider turtles has been found to decrease from ~30 bpm to ~2 bpm [&lt;span&gt;5&lt;/span&gt;]. This bradycardia results in an increase in stroke volume and greater diastolic pressures [&lt;span&gt;3&lt;/span&gt;]. To reduce the stress of an increase in cardiac preload, turtles have been demonstrated to decrease systemic resistance while decreasing the compliance of the ventricle [&lt;span&gt;3&lt;/span&gt;]. The increase in cardiac collagen with cold acclimation is thought to be responsible for this increase in passive stiffness [&lt;span&gt;3&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Keen et al. [&lt;span&gt;1&lt;/span&gt;] characterize the remodeling of the turtle heart with cold acclimation as well as the associated modifications to metabolic function. In this study, an increase in tissue stiffness was measured after 8 weeks of cold acclimation using atomic force microscopy, and it is suggested that this was due to an increase in the density of stiff collagen fibers throughout the myocardium. Histological methods confirmed the increase in collagen and demonstrated an increase in fiber alignment with cold acclimation. To identify the mechanisms responsible for the increase in collagen, the authors examined changes in the exp","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143879711","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":"Targeting Inflammation in Type 2 Diabetes: The Emerging Role of Decorin","authors":"Shayla Sharmine,&nbsp;Luiza Ghila","doi":"10.1111/apha.70049","DOIUrl":"https://doi.org/10.1111/apha.70049","url":null,"abstract":"&lt;p&gt;Type 2 diabetes (T2D) is a metabolic disease characterized by insulin resistance and progressive deterioration of pancreatic insulin-producing β-cell function, leading to chronic hyperglycemia. Although initially considered a “disease of the pancreas,” latest views acknowledge that optimal glycemic regulation involves complex and mutual communication between different organs and tissues including the pancreas, liver, intestine, brain, muscle and adipose tissue. Skeletal muscle has long been recognized as a metabolic organ [&lt;span&gt;1&lt;/span&gt;], producing myokines such as irisin and interleukin-6 (IL6) with key role in modulating insulin sensitivity and metabolic health [&lt;span&gt;2&lt;/span&gt;]. In a recent issue of Acta Physiologica, Langlois et al. [&lt;span&gt;3&lt;/span&gt;] provides novel insight to the role of another myokine, decorin, a promising protective factor involved in preserving the pancreatic β-cell function and insulin secretion under inflammatory conditions.&lt;/p&gt;&lt;p&gt;Myokines are proteins that are produced and released from skeletal muscle cells and act as hormones on other organs, including the pancreas, liver, brain, and adipose tissue [&lt;span&gt;1&lt;/span&gt;]. Decorin, a small leucine-rich proteoglycan [&lt;span&gt;4&lt;/span&gt;], has been established as a myokine [&lt;span&gt;5&lt;/span&gt;] (Figure 1), promoting muscle hypertrophy through inhibition of myostatin (MSTN, or growth and differentiation factor 8). MSTN is a member of the transforming growth factor-β (TGF-β) superfamily, having a crucial role in the negative regulation of muscle growth by suppressing both myoblast proliferation and myofibre hypertrophy. Higher levels of MSTN were detected in T2D but also in non-obese insulin-resistant patients. Also, MSTN was shown to inhibit glucose transporter 4 (GLUT4) and thus decrease muscle glucose uptake. Decorin, which binds and contributes to the stabilization of collagen fibers in the extracellular matrix (ECM) was shown to be produced by muscle activity and to sequester MSTN in the ECM, thus blocking its inhibitory effect on myoblast proliferation [&lt;span&gt;6&lt;/span&gt;] and potentially having also an indirect role in glucose regulation. But, can decorin act long-range as well?&lt;/p&gt;&lt;p&gt;Langlois et al. provided significant experimental insights into this muscle-pancreatic islet crosstalk by showing that decorin could also have a direct role on pancreatic islet cells. Applied in vitro, decorin protected the isolated β-cells and pancreatic islets from inflammatory stress. Recent studies showed that chronic low-grade inflammation leads to insulin signaling disruption, thus exacerbating β-cell stress leading to functional dysfunction and eventual cell loss [&lt;span&gt;7, 8&lt;/span&gt;]. Moreover, elevated levels of pro-inflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and interferon γ (IFN-γ) were previously shown to hinder glucose homeostasis and increase metabolic stress. Exposure to TNF-α typically impairs glucose-stimulated insulin secretion (GSIS), disrupt","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143875513","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":"Hemodynamics and Drinking in the Giraffe","authors":"Christian Aalkjær,&nbsp;Mads Damkjær,&nbsp;Ulrik T. Baandrup,&nbsp;Mads F. Bertelsen,&nbsp;Torbjørn Brøgger,&nbsp;Emil Brøndum,&nbsp;Carl C. Danielsen,&nbsp;Jonas A. Funder,&nbsp;Carsten Grøndahl,&nbsp;J. Michael Hasenkam,&nbsp;Per G. Henriksen,&nbsp;Niels H. Secher,&nbsp;Nini Skovgaard,&nbsp;Morten H. Smerup,&nbsp;Niklas Telinius,&nbsp;Kristine H. Østergaard,&nbsp;Peter Bie,&nbsp;Tobias Wang","doi":"10.1111/apha.70046","DOIUrl":"https://doi.org/10.1111/apha.70046","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The circulation of 4–6 m tall giraffes is markedly affected by gravity. To ensure cerebral perfusion, upright giraffes generate a blood pressure in excess of 200 mmHg. Before drinking, the head is lowered by 3–5 m, providing exceptional hemodynamic challenges. Here, we provide quantitative hemodynamic measures during head movement and drinking.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We measured carotid pressure, jugular pressure, heart rate, and blood flow in awake giraffes, along with circulating blood volume and cerebrospinal fluid pressure in anesthetized giraffes. We also analyzed the contractility and innervation of isolated cerebral and extracranial arteries, and the mechanical properties of jugular veins.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>When heads were lowered for drinking (i) blood pressure at heart level decreased but increased again during drinking, (ii) jugular pressure increased and oscillated during drinking, (iii) heart rate fell, (iv) carotid blood flow was unchanged, while cephalic hemodynamic resistance increased, and (vi) cranial cerebrospinal fluid pressure increased. Small cerebral arteries exhibited strong myogenic responses, particularly at around 100 mmHg, while extracranial arteries responded at higher pressures (200–250 mmHg). The giraffe's blood volume was small and blood pressure sensitive to minor reductions in blood volume.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Central blood pressure decreased when the head was lowered, but drinking per se caused a surprising rise in blood pressure to pre-drinking levels. This rise in blood pressure is likely due to the transfer of esophageal water boli acting on the jugular veins. The cephalic capillaries are protected by a strong myogenic response and sympathetic innervation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143856894","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}