Pflugers Archiv : European journal of physiology最新文献

{"title":"Characterization of human placental fetal vessels in gestational diabetes mellitus.","authors":"Philine S Carstens, Heike Brendel, M Leyre Villar-Ballesteros, Jennifer Mittag, Clara Hengst, Coy Brunssen, Cahit Birdir, Paul D Taylor, Lucilla Poston, Henning Morawietz","doi":"10.1007/s00424-024-03028-6","DOIUrl":"10.1007/s00424-024-03028-6","url":null,"abstract":"<p><p>Gestational diabetes mellitus is one of the most common complications during pregnancy. Its prevalence is rapidly increasing worldwide. Gestational diabetes mellitus is leading to an elevated risk for the development of endothelial dysfunction and cardiovascular diseases both in the mother and the child in later life. The underlying pathophysiological mechanisms are not well-understood. Therefore, we aimed to characterize the endothelial function in fetal placental vessels from mothers with gestational diabetes mellitus. In this study, we distinguished between insulin-treated and diet-controlled gestational diabetes mothers and compared them to a normoglycemic control group. The clinical data confirmed pre-conceptional overweight as a risk factor in women with insulin-treated gestational diabetes mellitus. The insulin-treated gestational diabetes group was also characterized by a recent family history of diabetes compared to mothers of the control or diet-controlled gestational diabetes group. Analyses of blood serum from umbilical cords suggested a reduced fetal insulin metabolism in the insulin-treated gestational diabetes group. Vascular function analysis in fetal placental vessels revealed an altered substance P-induced vasorelaxation in vessels from patients with insulin-dependent gestational diabetes. Inhibition of nitric oxide synthase affected only fetal vessel segments from the control group or diet-controlled gestational diabetes group, but not from insulin-dependent gestational diabetes. Finally, we found a significantly decreased substance P receptor (TACR1) mRNA expression in fetal vessel segments from patients with insulin-treated gestational diabetes. In conclusion, we provide evidence that different pathophysiological mechanisms might be responsible for the development of insulin-treated versus diet-controlled gestational diabetes. Only in fetal vessels from patients with insulin-treated gestational diabetes were we able to detect an endothelial dysfunction and a reduced fetal insulin conversion. This provides novel insights into the pathophysiology of the subtypes of gestational diabetes.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"67-79"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11711144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392406","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":"A dendrite is a dendrite is a dendrite? Dendritic signal integration beyond the \"antenna\" model.","authors":"Moritz Stingl, Andreas Draguhn, Martin Both","doi":"10.1007/s00424-024-03004-0","DOIUrl":"10.1007/s00424-024-03004-0","url":null,"abstract":"<p><p>Neurons in central nervous systems receive multiple synaptic inputs and transform them into a largely standardized output to their target cells-the action potential. A simplified model posits that synaptic signals are integrated by linear summation and passive propagation towards the axon initial segment, where the threshold for spike generation is either crossed or not. However, multiple lines of research during past decades have shown that signal integration in individual neurons is much more complex, with important functional consequences at the cellular, network, and behavioral-cognitive level. The interplay between concomitant excitatory and inhibitory postsynaptic potentials depends strongly on the relative timing and localization of the respective synapses. In addition, dendrites contain multiple voltage-dependent conductances, which allow scaling of postsynaptic potentials, non-linear input processing, and compartmentalization of signals. Together, these features enable a rich variety of single-neuron computations, including non-linear operations and synaptic plasticity. Hence, we have to revise over-simplified messages from textbooks and use simplified computational models like integrate-and-fire neurons with some caution. This concept article summarizes the most important mechanisms of dendritic integration and highlights some recent developments in the field.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"9-16"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11711151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142004926","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":"Optimization of an autaptic culture system for studying cholinergic synapses in sympathetic ganglia.","authors":"Seong Jun Kang, Huu Son Nguyen, Choong-Ku Lee, Sohyun Kim, Jeong Seop Rhee, Seong-Woo Jeong","doi":"10.1007/s00424-024-03023-x","DOIUrl":"10.1007/s00424-024-03023-x","url":null,"abstract":"<p><p>An autaptic synapse (or 'autapse') is a functional connection between a neuron and itself, commonly used in studying the molecular mechanisms underlying synaptic transmission and plasticity in central neurons. Most previous studies on autonomic synaptic functions have relied on spontaneous connections among neurons in mass cultures. However, growing evidence supports the utility of microcultures cultivating autaptic neurons for examining cholinergic transmission within sympathetic ganglia. Despite these advancements, standardized protocols for culturing autaptic sympathetic neurons have yet to be established. Drawing on historical literature, this study delineates optimal experimental conditions to efficiently and reliably produce cholinergic synapses in sympathetic neurons within a short time frame. Our research emphasizes five key factors: (i) the generation of uniformly sized microislands of growth permissive substrates; (ii) the addition of nerve growth factor, ciliary neurotrophic factor (CNTF), and serum to the culture medium; (iii) independence from specific serum and neuronal medium types; (iv) the reciprocal roles of CNTF and glial cells; and (v) the promotion of cholinergic synaptogenesis in SCG neurons through indirect glia co-cultures, rather than direct glial feeder layer cultures. In conclusion, glia-free monocultures of SCG neurons are relatively simple to prepare and yield robust and reliable synaptic currents. This makes them an effective model system for straightforwardly addressing fundamental questions about neurogenic mechanisms involved in cholinergic synaptic transmission in autonomic ganglia. Furthermore, autaptic culture experiments could eventually be implemented to investigate the roles of functional neuron-satellite glia units in regulating cholinergic functions under physiological and pathological conditions.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"111-129"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiological regulation of oral saliva ion composition and flow rate are not coupled in healthy humans-Partial revision of our current knowledge required.","authors":"Gerald Schwerdt, Marie-Christin Schulz, Michael Kopf, Sigrid Mildenberger, Sarah Reime, Michael Gekle","doi":"10.1007/s00424-024-03025-9","DOIUrl":"10.1007/s00424-024-03025-9","url":null,"abstract":"<p><p>Appropriate composition of oral saliva is essential for a healthy milieu that protects mucosa and teeth. Only few studies, with small sample numbers, investigated physiological saliva ion composition in humans. We determined saliva ion composition in a sufficiently large cohort of healthy adults and analyzed the effect of physiological stimulation. We collected saliva from 102 adults under non-stimulated and physiologically stimulated conditions (chewing). Individual flow rates, pH, osmolality, Na⁺, K⁺, Cl^-, and HCO₃^- concentrations under both conditions as well as the individual changes due to stimulation (Δvalues) were determined. Non-stimulated saliva was hypoosmolal and acidic. Na⁺, Cl^-, and HCO₃^- concentrations remained well below physiological plasma values, whereas K⁺ concentrations exceeded plasma values more than twofold. Stimulation resulted in a doubling of flow rates and substantial increases in pH, HCO₃^-, and Na⁺ concentrations. Overall, stimulation did not considerably affect osmolality nor K⁺ or Cl^- concentrations of saliva. An in-depth analysis of stimulation effects, using individual Δvalues, showed no correlation of Δflow rate with Δion concentrations, indicating independent regulation of acinar volume and ductal ion transport. Stimulation-induced Δ[Na⁺] correlated with Δ[HCO₃^-] and Δ[Cl^-] but not with Δ[K⁺], indicating common regulation of ductal Na⁺, Cl^-, and HCO₃^- transport. We present a robust data set of human oral saliva ion composition in healthy adults and functional insights into physiological stimulation. Our data show (i) that flow-dependence exists for Na⁺ and HCO₃^- but not for K⁺ and Cl^- concentrations, (ii) osmolality is flow-independent, (iii) regulation of Na⁺, Cl^-, and HCO₃^- transport is coupled, (iv) regulation of flow rate and ion concentrations are independent and (v) spatially separated between acini and ducts, respectively.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"55-65"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11711875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361899","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":"Correction to: Intertwined regulators: hypoxia pathway proteins, microRNAs, and phosphodiesterases in the control of steroidogenesis.","authors":"Stephen Ariyeloye, Susanne Kämmerer, Erik Klapproth, Ben Wielockx, Ali El-Armouche","doi":"10.1007/s00424-024-03044-6","DOIUrl":"10.1007/s00424-024-03044-6","url":null,"abstract":"","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"169"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11711148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731755","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":"Correction to: Characterization of human placental fetal vessels in gestational diabetes mellitus.","authors":"Philine S Carstens, Heike Brendel, M Leyre Villar-Ballesteros, Jennifer Mittag, Clara Hengst, Coy Brunssen, Cahit Birdir, Paul D Taylor, Lucilla Poston, Henning Morawietz","doi":"10.1007/s00424-024-03052-6","DOIUrl":"10.1007/s00424-024-03052-6","url":null,"abstract":"","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"81"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11711861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807586","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":"Nobel Prize for physiology or medicine in 2024 for the discovery of microRNAs: small RNAs with fundamental roles in development and disease.","authors":"Miguel Quévillon Huberdeau, Gunter Meister","doi":"10.1007/s00424-024-03053-5","DOIUrl":"10.1007/s00424-024-03053-5","url":null,"abstract":"","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"35-36"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11711248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807600","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":"GQ style: a multipronged therapeutic approach to pulmonary arterial hypertension.","authors":"Wolfgang M Kuebler","doi":"10.1007/s00424-024-03056-2","DOIUrl":"10.1007/s00424-024-03056-2","url":null,"abstract":"","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"31-33"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11711705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142837058","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":"Something old, something new, something borrowed, something blue and a silver sixpence in her shoe.","authors":"Carsten A Wagner","doi":"10.1007/s00424-024-03055-3","DOIUrl":"https://doi.org/10.1007/s00424-024-03055-3","url":null,"abstract":"","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A role for plasma membrane Ca²⁺ ATPases in regulation of cellular Ca²⁺ homeostasis by sphingosine kinase-1.","authors":"Luisa Michelle Volk, Jan-Erik Bruun, Sandra Trautmann, Dominique Thomas, Stephanie Schwalm, Josef Pfeilschifter, Dagmar Meyer Zu Heringdorf","doi":"10.1007/s00424-024-03027-7","DOIUrl":"10.1007/s00424-024-03027-7","url":null,"abstract":"<p><p>Sphingosine-1-phosphate (S1P) is a ubiquitous lipid mediator, acting via specific G-protein-coupled receptors (GPCR) and intracellularly. Previous work has shown that deletion of S1P lyase caused a chronic elevation of cytosolic [Ca²⁺]_i and enhanced Ca²⁺ storage in mouse embryonic fibroblasts. Here, we studied the role of sphingosine kinase (SphK)-1 in Ca²⁺ signaling, using two independently generated EA.hy926 cell lines with stable knockdown of SphK1 (SphK1-KD1/2). Resting [Ca²⁺]_i and thapsigargin-induced [Ca²⁺]_i increases were reduced in both SphK1-KD1 and -KD2 cells. Agonist-induced [Ca²⁺]_i increases, measured in SphK1-KD1, were blunted. In the absence of extracellular Ca²⁺, thapsigargin-induced [Ca²⁺]_i increases declined rapidly, indicating enhanced removal of Ca²⁺ from the cytosol. In agreement, plasma membrane Ca²⁺ ATPase (PMCA)-1 and -4 and their auxiliary subunit, basigin, were strongly upregulated. Activation of S1P-GPCR by specific agonists or extracellular S1P did not rescue the effects of SphK1 knockdown, indicating that S1P-GPCR were not involved. Lipid measurements indicated that not only S1P but also dihydro-sphingosine, ceramides, and lactosylceramides were markedly depleted in SphK1-KD2 cells. SphK2 and S1P lyase were upregulated, suggesting enhanced flux via the sphingolipid degradation pathway. Finally, histone acetylation was enhanced in SphK1-KD2 cells, and the histone deacetylase inhibitor, vorinostat, induced upregulation of PMCA1 and basigin on mRNA and protein levels in EA.hy926 cells. These data show for the first time a transcriptional regulation of PMCA1 and basigin by S1P metabolism. It is concluded that SphK1 knockdown in EA.hy926 cells caused long-term alterations in cellular Ca²⁺ homeostasis by upregulating PMCA via increased histone acetylation.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"1895-1911"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11582158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400969","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}