Pflugers Archiv : European journal of physiology最新文献

Spatially dependent tissue distribution of thyroid hormones by plasma thyroid hormone binding proteins.

IF 2.9 4区医学

Pflugers Archiv : European journal of physiology Pub Date : 2025-01-03 DOI: 10.1007/s00424-024-03060-6

Anish D Bagga, Brian P Johnson, Qiang Zhang

{"title":"Spatially dependent tissue distribution of thyroid hormones by plasma thyroid hormone binding proteins.","authors":"Anish D Bagga, Brian P Johnson, Qiang Zhang","doi":"10.1007/s00424-024-03060-6","DOIUrl":"https://doi.org/10.1007/s00424-024-03060-6","url":null,"abstract":"Plasma thyroid hormone (TH) binding proteins (THBPs), including thyroxine-binding globulin (TBG), transthyretin (TTR), and albumin (ALB), carry THs to extrathyroidal sites, where THs are unloaded locally and then taken up via membrane transporters into the tissue proper. The respective roles of THBPs in supplying THs for tissue uptake are not completely understood. To investigate this, we developed a spatial human physiologically based kinetic (PBK) model of THs, which produces several novel findings. (1) Contrary to postulations that TTR and/or ALB are the major local T4 contributors, the three THBPs may unload comparable amounts of T4 in Liver, a rapidly perfused organ; however, their contributions in slowly perfused tissues follow the order of abundances of T4TBG, T4TTR, and T4ALB. The T3 amounts unloaded from or loaded onto THBPs in a tissue acting as a T3 sink or source respectively follow the order of abundance of T3TBG, T3ALB, and T3TTR regardless of perfusion rate. (2) Any THBP alone is sufficient to maintain spatially uniform TH tissue distributions. (3) The TH amounts unloaded by each THBP species are spatially dependent and nonlinear in a tissue, with ALB being the dominant contributor near the arterial end but conceding to TBG near the venous end. (4) Spatial gradients of TH transporters and metabolic enzymes may modulate these contributions, producing spatially invariant or heterogeneous TH tissue concentrations depending on whether the blood-tissue TH exchange operates in near-equilibrium mode. In summary, our modeling provides novel insights into the differential roles of THBPs in local TH tissue distribution.","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922508","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}

引用次数: 0

Competing effects of activation history on force and cytosolic Ca²⁺ in intact single mice myofibers.

IF 2.9 4区医学

Pflugers Archiv : European journal of physiology Pub Date : 2024-12-30 DOI: 10.1007/s00424-024-03061-5

Alexander M Zero, Charles L Rice, Leonardo Nogueira

{"title":"Competing effects of activation history on force and cytosolic Ca2+ in intact single mice myofibers.","authors":"Alexander M Zero, Charles L Rice, Leonardo Nogueira","doi":"10.1007/s00424-024-03061-5","DOIUrl":"https://doi.org/10.1007/s00424-024-03061-5","url":null,"abstract":"The purpose was to investigate the changes in cytosolic Ca2+ and force output during post-tetanic potentiation (PTP) during pre-fatigue and during prolonged low-frequency force depression (PLFFD) following fatigue. Intact single myofibers from the flexor digitorum brevis of mice were electrically stimulated to record force (n = 8) and free cytosolic Ca2+ concentration ([Ca2+]c) with FURA-2 (n = 6) at 32 °C. Initially, force and [Ca2+]c were measured during brief (350 ms) trains of stimuli at 30, 50, 70, and 200 Hz at ~ 2 s intervals (Force-frequency protocol, FFP). Then, a conditioning stimulus (CS) of six 120 Hz stimuli, separated by ~ 3 s, was used to induce PTP, immediately followed by an FFP. Myofiber fatigue was produced by 150 Hz trains every 3 s until peak force decayed 70% of the initial. Thirty minutes after the fatigue, the CS was repeated to assess the effect of PTP on force and [Ca2+]c during PLFFD. The CS in unfatigued myofibers induced PTP as the submaximal force was enhanced and accompanied by increased peak [Ca2+]c with no change in myofilament Ca2+ sensitivity. After fatigue, PLFFD was due to lowered peak [Ca2+]c. Inducing PTP during PLFFD enhanced submaximal force primarily through greater peak [Ca2+]c, mitigating the submaximal force deficits. Despite the impaired force during PLFFD, myofibers remained sensitive to PTP, and this mitigated the submaximal force deficits through increased peak [Ca2+]c without a change in myofilament Ca2+ sensitivity. Therefore, force adjustments of intact single myofibers due to activation history are principally accomplished by opposing adjustments in [Ca2+]c.","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142910059","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}

引用次数: 0

Hyperosmolality activates polycystin-2 and TRPM4 in renal primary cilium.

IF 2.9 4区医学

Pflugers Archiv : European journal of physiology Pub Date : 2024-12-17 DOI: 10.1007/s00424-024-03050-8

Steven J Kleene

{"title":"Hyperosmolality activates polycystin-2 and TRPM4 in renal primary cilium.","authors":"Steven J Kleene","doi":"10.1007/s00424-024-03050-8","DOIUrl":"https://doi.org/10.1007/s00424-024-03050-8","url":null,"abstract":"Autosomal dominant polycystic kidney disease (ADPKD) is a debilitating disease characterized by renal cysts. It arises from mutations in proteins expressed in part in the primary cilia of renal epithelial cells. One of these, polycystin-2 (PC2), is an ion-conducting channel. To date, ion channels in the cilium have only been characterized in standard normosmolar external solutions, but the osmolality of the renal filtrate bathing the cilia varies widely. Here I report that urine, which better represents the filtrate, activates a large cation-conducting current in the cilia. With defined external solutions, hyperosmolality through addition of urea, NaCl, or D-mannitol activates a similar current. Most but not all of this current is conducted through TRPM4 channels. It is greatly reduced by internal MgATP or 9-phenanthrol, which inhibit TRPM4, or by shRNA knockdown of TRPM4. However, part of the current activated by urea conducts Ca2+ through channels that remain to be identified. External hyperosmolality also greatly increases the activity of ciliary PC2 channels; this is the first physiological stimulus identified for these channels. Possibilities are discussed for the mechanisms of channel activation and the roles for these activities in regulatory volume increase and cystogenesis.","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142837744","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}

引用次数: 0

GQ style: a multipronged therapeutic approach to pulmonary arterial hypertension. GQ风格：多管齐下的肺动脉高压治疗方法。

IF 2.9 4区医学

Pflugers Archiv : European journal of physiology Pub Date : 2024-12-17 DOI: 10.1007/s00424-024-03056-2

Wolfgang M Kuebler

引用次数: 0

An Editor-in-Chief's farewell.

IF 2.9 4区医学

Pflugers Archiv : European journal of physiology Pub Date : 2024-12-12 DOI: 10.1007/s00424-024-03054-4

Armin Kurtz

引用次数: 0

Something old, something new, something borrowed, something blue and a silver sixpence in her shoe.

IF 2.9 4区医学

Pflugers Archiv : European journal of physiology Pub Date : 2024-12-11 DOI: 10.1007/s00424-024-03055-3

Carsten A Wagner

引用次数: 0

Correction to: Characterization of human placental fetal vessels in gestational diabetes mellitus.

IF 2.9 4区医学

Pflugers Archiv : European journal of physiology Pub Date : 2024-12-11 DOI: 10.1007/s00424-024-03052-6

Philine S Carstens, Heike Brendel, M Leyre Villar-Ballesteros, Jennifer Mittag, Clara Hengst, Coy Brunssen, Cahit Birdir, Paul D Taylor, Lucilla Poston, Henning Morawietz

引用次数: 0

Nobel Prize for physiology or medicine in 2024 for the discovery of microRNAs: small RNAs with fundamental roles in development and disease.

IF 2.9 4区医学

Pflugers Archiv : European journal of physiology Pub Date : 2024-12-11 DOI: 10.1007/s00424-024-03053-5

Miguel Quévillon Huberdeau, Gunter Meister

引用次数: 0

Effects of tDCS on glutamatergic pathways in epilepsy: neuroprotective and therapeutic potential.

IF 2.9 4区医学

Pflugers Archiv : European journal of physiology Pub Date : 2024-12-07 DOI: 10.1007/s00424-024-03049-1

Filiz Demirdogen, Guven Akcay

{"title":"Effects of tDCS on glutamatergic pathways in epilepsy: neuroprotective and therapeutic potential.","authors":"Filiz Demirdogen, Guven Akcay","doi":"10.1007/s00424-024-03049-1","DOIUrl":"https://doi.org/10.1007/s00424-024-03049-1","url":null,"abstract":"Epilepsy is a chronic neurological disease characterized by recurrent seizures caused by abnormal electrical activity in the brain. The aim of our study was to investigate the effect of tDCS on oxidative stress, Ca2+, glutamate, GABA, AMPAR1, and NMDAR1 levels in kindling-induced epilepsy model. Behavioral tests evaluated motor and cognitive functions, while assessing oxidative stress, Ca2+, glutamate, GABA, AMPAR1, and NMDAR1 levels in hippocampal tissue. tDCS stimulation therapy demonstrates a neuroprotective effect on motor and cognitive function postepilepsy. Our study reveals an increase in TOC, Ca2+, glutamate, GABA, AMPAR1, and NMDAR1 levels and a decline in total antioxidant capacity (TAC) following PTZ-induced seizures. However, tDCS treatment led to a significant decrease of Ca2+, total oxidant capacity (TOC), glutamate, GABA, AMPAR1, and NMDAR1 levels in the epilepsy cohorts, while simultaneously causing a spike in TAC levels. The study's results showed that tDCS treatment could have a therapeutic effect on oxidative stress, Ca2+, TOC, glutamate, GABA, AMPAR1, NMDAR1, and TAC in both acute and chronic kindling epilepsy models.","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791706","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}

引用次数: 0

Novel neural pathways targeted by GLP-1R agonists and bariatric surgery.

IF 2.9 4区医学

Pflugers Archiv : European journal of physiology Pub Date : 2024-12-07 DOI: 10.1007/s00424-024-03047-3

Mohammed K Hankir, Thomas A Lutz

{"title":"Novel neural pathways targeted by GLP-1R agonists and bariatric surgery.","authors":"Mohammed K Hankir, Thomas A Lutz","doi":"10.1007/s00424-024-03047-3","DOIUrl":"https://doi.org/10.1007/s00424-024-03047-3","url":null,"abstract":"The glucagon-like peptide 1 receptor (GLP-1R) agonist semaglutide has revolutionized the treatment of obesity, with other gut hormone-based drugs lined up that show even greater weight-lowering ability in obese patients. Nevertheless, bariatric surgery remains the mainstay treatment for severe obesity and achieves unparalleled weight loss that generally stands the test of time. While their underlying mechanisms of action remain incompletely understood, it is clear that the common denominator between GLP-1R agonists and bariatric surgery is that they suppress food intake by targeting the brain. In this Review, we highlight recent preclinical studies using contemporary neuroscientific techniques that provide novel concepts in the neural control of food intake and body weight with reference to endogenous GLP-1, GLP-1R agonists, and bariatric surgery. We start in the periphery with vagal, intestinofugal, and spinal sensory nerves and then progress through the brainstem up to the hypothalamus and finish at non-canonical brain feeding centers such as the zona incerta and lateral septum. Further defining the commonalities and differences between GLP-1R agonists and bariatric surgery in terms of how they target the brain may not only help bridge the gap between pharmacological and surgical interventions for weight loss but also provide a neural basis for their combined use when each individually fails.","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791771","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}

引用次数: 0