Current research in physiology最新文献

{"title":"Long-term Xenopus laevis tadpole -heart-organ-culture: Physiological changes in cholinergic and adrenergic sensitivities of tadpole heart with thyroxine-treatment","authors":"Hideki Hanada ,&nbsp;Fumihiro Morishita ,&nbsp;Seigo Sanoh ,&nbsp;Keiko Kashiwagi ,&nbsp;Akihiko Kashiwagi","doi":"10.1016/j.crphys.2023.100100","DOIUrl":"https://doi.org/10.1016/j.crphys.2023.100100","url":null,"abstract":"<div><p>The present study clarified changes in physiological sensitivities of cultured Nieuwkoop and Faber stage 57 <em>Xenopus laevis</em> tadpole-organ-heart exposed to thyroxine (T₄) using acetylcholine (ACh), norepinephrine (NE) and atropine. For preliminary life span and the chemical tests, 60% minimum essential medium (MEM), two types of modified Hank's balanced salt-solution-culture-media (MHBSS-CM) I and II containing relatively lower concentrations of amino acids and collagen were prepared. In preliminary lifespan-test of cultured tadpole hearts, the hearts maintained in 60% MEM was 50 days on average, whereas that of the tadpole-hearts in MHBSS-CMs was extended by 109 days on average, showing superior effectiveness of MHBSS-CMs. 4 min-stimulation by 5 × 10⁻⁹ M T₄ tended to increase the tadpole heartbeat. 10⁻⁹ M ACh decreased the tadpole heartbeat. Frog-heart at 2–4 weeks after metamorphosis completion and tadpole heart treated with 5 × 10⁻¹⁰ M T₄ for 45 h also responded to 10⁻⁹ M ACh, and low-resting hearts were restored to the control level with the competitive muscarinic antagonist 10⁻⁸ M atropine, whereas excessive exposure of 10⁻⁵ M atropine to T₄-treated tadpole heart did not increase heartbeat in spite of the increased frog heartbeat over the control. 10⁻¹⁴ —10⁻¹² M NE increase the tadpole heartbeat in a concentration-dependent manner, however, 10⁻¹² M NE did not act to stimulate adrenergic receptors on both T₄-treated tadpole- and the frog-hearts. These results suggest that T₄ induces the desensitization of atropine-sensitive muscarinic and adrenergic receptors in organ-cultured tadpole-heart.</p></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"6 ","pages":"Article 100100"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49775952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dopamine transporter membrane mobility is bidirectionally regulated by phosphorylation and palmitoylation","authors":"Madhur Shetty,&nbsp;Danielle E. Bolland ,&nbsp;Joshua Morrell,&nbsp;Bryon D. Grove,&nbsp;James D. Foster,&nbsp;Roxanne A. Vaughan","doi":"10.1016/j.crphys.2023.100106","DOIUrl":"https://doi.org/10.1016/j.crphys.2023.100106","url":null,"abstract":"<div><p>The primary regulator of dopamine availability in the brain is the dopamine transporter (DAT), a plasma membrane protein that drives reuptake of released dopamine from the extracellular space into the presynaptic neuron. DAT activity is regulated by post-translational modifications that establish clearance capacity through impacts on transport kinetics, and dysregulation of these events may underlie dopaminergic imbalances in mood and psychiatric disorders. Here, using fluorescence recovery after photobleaching, we show that phosphorylation and palmitoylation induce opposing effects on DAT lateral membrane mobility, which may influence functional outcomes by regulating subcellular localization and binding partner interactions. Membrane mobility was also impacted by amphetamine and in polymorphic variant A559V in directions consistent with enhanced phosphorylation. These findings grow the list of DAT properties controlled by these post-translational modifications and highlight their role in establishment of dopaminergic tone in physiological and pathophysiological states.</p></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"6 ","pages":"Article 100106"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49775955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precise CRISPR-Cas9-mediated mutation of a membrane trafficking domain in the Drosophila vesicular monoamine transporter gene","authors":"James D. Asuncion ,&nbsp;Aditya Eamani ,&nbsp;Ethan W. Rohrbach ,&nbsp;Elizabeth M. Knapp ,&nbsp;Sonali A. Deshpande ,&nbsp;Shivan L. Bonanno ,&nbsp;Jeremy E. Murphy ,&nbsp;Hakeem O. Lawal ,&nbsp;David E. Krantz","doi":"10.1016/j.crphys.2023.100101","DOIUrl":"https://doi.org/10.1016/j.crphys.2023.100101","url":null,"abstract":"<div><p>Monoamine neurotransmitters such as noradrenalin are released from both synaptic vesicles (SVs) and large dense-core vesicles (LDCVs), the latter mediating extrasynaptic signaling. The contribution of synaptic versus extrasynaptic signaling to circuit function and behavior remains poorly understood. To address this question, we have previously used transgenes encoding a mutation in the <em>Drosophila</em> Vesicular Monoamine Transporter (<em>dVMAT</em>) that shifts amine release from SVs to LDCVs. To circumvent the use of transgenes with non-endogenous patterns of expression, we have now used CRISPR-Cas9 to generate a trafficking mutant in the endogenous <em>dVMAT</em> gene. To minimize disruption of the <em>dVMAT</em> coding sequence and a nearby RNA splice site, we precisely introduced a point mutation using single-stranded oligonucleotide repair. A predicted decrease in fertility was used as a phenotypic screen to identify founders in lieu of a visible marker. Phenotypic analysis revealed a defect in the ovulation of mature follicles and egg retention in the ovaries. We did not detect defects in the contraction of lateral oviducts following optogenetic stimulation of octopaminergic neurons. Our findings suggest that release of mature eggs from the ovary is disrupted by changing the balance of VMAT trafficking between SVs and LDCVs. Further experiments using this model will help determine the mechanisms that sensitize specific circuits to changes in synaptic versus extrasynaptic signaling.</p></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"6 ","pages":"Article 100101"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49775956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioengineering and the cervix: The past, current, and future for addressing preterm birth","authors":"Kyoko Yoshida","doi":"10.1016/j.crphys.2023.100107","DOIUrl":"https://doi.org/10.1016/j.crphys.2023.100107","url":null,"abstract":"<div><p>The uterine cervix plays two important but opposing roles during pregnancy – as a mechanical barrier that maintains the fetus for nine months and as a compliant structure that dilates to allow for the delivery of a baby. In some pregnancies, however, the cervix softens and dilates prematurely, leading to preterm birth. Bioengineers have addressed and continue to address the lack of reduction in preterm birth rates by developing novel technologies to diagnose, prevent, and understand premature cervical remodeling. This article highlights these existing and emerging technologies and concludes with open areas of research related to the cervix and preterm birth that bioengineers are currently well-positioned to address.</p></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"6 ","pages":"Article 100107"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49775957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomechanical remodeling of the murine descending thoracic aorta during late-gestation pregnancy","authors":"Ana I. Vargas ,&nbsp;Samar A. Tarraf ,&nbsp;Timothy P. Fitzgibbons ,&nbsp;Chiara Bellini ,&nbsp;Rouzbeh Amini","doi":"10.1016/j.crphys.2023.100102","DOIUrl":"10.1016/j.crphys.2023.100102","url":null,"abstract":"<div><p>With the rise in maternal mortality rates and the growing body of epidemiological evidence linking pregnancy history to maternal cardiovascular health, it is essential to comprehend the vascular remodeling that occurs during gestation. The maternal body undergoes significant hemodynamic alterations which are believed to induce structural remodeling of the cardiovascular system. Yet, the effects of pregnancy on vascular structure and function have not been fully elucidated. Such a knowledge gap has limited our understanding of the etiology of pregnancy-induced cardiovascular disease. Towards bridging this gap, we measured the biaxial mechanical response of the murine descending thoracic aorta during a normotensive late-gestation pregnancy. Non-invasive hemodynamic measurements confirmed a 50% increase in cardiac output in the pregnant group, with no changes in peripheral blood pressure. Pregnancy was associated with significant wall thickening ( ∼14%), an increase in luminal diameter ( ∼6%), and material softening in both circumferential and axial directions. This expansive remodeling of the tissue resulted in a reduction in tensile wall stress and intrinsic tissue stiffness. Collectively, our data indicate that an increase in the geometry of the vessel may occur to accommodate for the increase in cardiac output and blood flow that occurs in pregnancy. Similarly, wall thickening accompanied by increased luminal diameter, without a change in blood pressure may be a necessary mechanism to decrease the tensile wall stress, and avoid pathophysiological events following late gestation.</p></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"6 ","pages":"Article 100102"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ad/d5/main.PMC10415834.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10351519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple pregnancies, the myometrium and the role of mechanical factors in the timing of labour","authors":"Sarah Arrowsmith","doi":"10.1016/j.crphys.2023.100105","DOIUrl":"10.1016/j.crphys.2023.100105","url":null,"abstract":"<div><p>Multiple pregnancy remains a relatively common occurrence, but it is associated with increased risks of adverse outcomes for the mother and her babies and presents unique challenges to healthcare providers. This review will briefly discuss multiple pregnancies, their aetiology and their problems, including preterm birth, before reviewing the processes leading to normal labour onset and how they may be different in a multiple pregnancy. The mechanisms by which mechanical factors i.e., uterine distension or ‘stretch’ contribute to uterine excitability and the timing of labour onset will be the major focus, and how over distention may pre-dispose multiple pregnancies to preterm birth. This includes current thinking around the role of mechano (stretch) sensitive ion channels in the myometrium and changes to other important regulators of excitability and contraction which have been identified from studies using <em>in vitro</em> and <em>in vivo</em> models of uterine stretch. Physiological stimuli arising from the fetus(es) and placenta(s) will also be discussed. In reviewing what we know about the myometrium in multiple pregnancy in humans, the focus will be on twin pregnancy as it is the most common type of multiple pregnancy and has been the most studied.</p></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"6 ","pages":"Article 100105"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48807415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pulmonary functions and anthropometric parameters of young male and female adults participating in moderate aerobic exercise","authors":"Idara A. Okon ,&nbsp;Albert E. Okorocha ,&nbsp;Justin A. Beshel ,&nbsp;Happiness C. Abali ,&nbsp;Daniel U. Owu","doi":"10.1016/j.crphys.2023.100112","DOIUrl":"https://doi.org/10.1016/j.crphys.2023.100112","url":null,"abstract":"<div><p>Respiratory disorders may be one of the adverse effects of sedentary lifestyle. This study investigated respiratory functions (FEV₁, FVC and PEFR) and anthropometric parameters (body weight and body mass index) of healthy young males and females participating in moderate aerobic exercise<strong>.</strong> Forty young healthy untrained non-athletes, twenty males and twenty females (age, 25 ± 5.6 years; body weight, 65 ± 4.0 kg; body height, 176.9 ± 2.5 cm) volunteered to participate in this study. The exercise regimen was of moderate intensity lasting for 20 min daily on a treadmill consistently at the speed of 13 km/h for 14 days. The weight and height of participants were measured using medical scale and wall-mounted stadiometer respectively. The forced expiratory volume in 1 s (FEV₁), forced vital capacity (FVC) and peak expiratory flow rate (PEFR) were assessed using digital spirometer. The results showed a significant (p &lt; 0.05) decrease in body weight and body mass index of female participants after 14 days of exercise regimen. The FEV₁, FVC and PEFR were significantly increased (p &lt; 0.05) in both male and female subjects after exercise. The Pearson correlation showed a significant (p &lt; 0.05) positive correlation between BMI with FEV_I/FVC% in female participants. There was an increase in calories burnt from day 4 of the study in both male and female participants. It is concluded that moderate aerobic exercise improved respiratory functions (FEV₁, FVC and PEFR) in both male and female subjects with greater improvement in females while reducing body weight and body mass index in females.</p></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"6 ","pages":"Article 100112"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49817356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of oxytocin-induced calcium transients and gene expression in engineered myometrial tissues by tissue architecture and matrix rigidity","authors":"Antonina P. Maxey ,&nbsp;Jaya M. Travis ,&nbsp;Megan L. McCain","doi":"10.1016/j.crphys.2023.100108","DOIUrl":"https://doi.org/10.1016/j.crphys.2023.100108","url":null,"abstract":"<div><p>The uterus is susceptible to benign tumors known as fibroids, which have been associated with many pregnancy complications, including preterm labor. However, the impact of fibrotic tissue remodeling on the physiology of the myometrium, the smooth muscle layer of the uterus, is poorly understood, in large part due to a lack of model systems. In this study, we engineered healthy-like and fibrotic-like myometrium by culturing human myometrial smooth muscle cells on polyacrylamide hydrogels micropatterned with fibronectin to independently tune matrix rigidity and tissue alignment, respectively. We then evaluated calcium transients in response to oxytocin stimulation. Isotropic myometrial tissues on stiff substrates (representing fibrotic myometrium) had shorter calcium transients due to shorter decay time compared to aligned myometrial tissues on soft substrates (representing healthy myometrium). Calcium transients in aligned tissues had longer response times and longer decay times than isotropic tissues, irrespective of substrate stiffness. The amplitude of calcium transients was also higher on soft substrates compared to stiff substrates, irrespective of tissue alignment. We also performed RNA sequencing to detect differentially expressed genes between healthy- and fibrotic-like tissues, which revealed that a bitter taste receptor shown to induce smooth muscle relaxation, <em>TAS2R31,</em> was down-regulated in fibrotic-like tissues. Finally, we measured oxytocin-induced calcium transients in response to pre-treatment with progesterone, caffeine, thrombin, and nifedipine to demonstrate applications for our model system in drug screening. Both progesterone and caffeine caused a decrease in calcium transient duration, as expected, while thrombin and nifedipine had less impact. Collectively, our engineered model of the myometrium enables new insights into myometrial mechanobiology and can be extended to identify or screen novel drug targets.</p></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"6 ","pages":"Article 100108"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49775933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"L-Arginine supplementation enhanced expression of glucose transporter (GLUT 1) in sickle cell anaemia subjects in the steady state","authors":"W.A. Saka ,&nbsp;C.N. Anigbogu ,&nbsp;M.O. Kehinde ,&nbsp;S.I. Jaja","doi":"10.1016/j.crphys.2022.11.003","DOIUrl":"10.1016/j.crphys.2022.11.003","url":null,"abstract":"<div><p>L-Arginine may have therapeutic value in the management of sickle cell disease and diabetes mellitus. There is very little information on the interaction of GLUT 1 and L-Arginine in sickle cell disease subjects. This study compared the blood levels of Glut 1, fasting blood glucose (FBG) and fasting insulin (FIns) in non-sickle cell anaemia (HbAA) and sickle cell anaemia (HbSS) subjects in the steady state before and following L-Arginine supplementation (1 g/day for 6 weeks). Nitric oxide metabolites, (NO_X), catalase, superoxide dismutase and glutathione peroxidase were also measured in each group of subjects. Correlation coefficients between change (Δ) in Glut 1 and change (Δ) in FBG, Fins, NO_X and antioxidant enzymes respectively were calculated. Before supplementation, Glut 1, NO_X, GP_X and CAT were significantly higher in HbAA subjects while FIns, FBG and MDA were higher in HbSS subjects. In both groups, supplementation significantly increased NO_X, Glut 1 and antioxidant enzymes but decreased MDA. Supplementation increased FIns in HbAA but decreased FBG and FIns in HbSS subjects. In both groups of subjects, ΔGLUT 1 correlated positively with ΔNOX, antioxidant enzymes and Δ[R] but negatively with ΔMDA. ΔGLUT 1 correlated negatively with ΔFBG and ΔFins in HbSS but positively in HbAA. Study thus showed that in the steady state HbSS subjects had lower GLUT 1 but elevated FBG and Fins levels than HbAA subjects. Additionally, L-Arginine increased GLUT I and antioxidant enzymes but decreased Fins, FBG and MDA in HbSS subjects.</p></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"6 ","pages":"Article 100096"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/38/4a/main.PMC9747353.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10424714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiological levels of cardiolipin acutely affect mitochondrial respiration in vascular smooth muscle cells","authors":"Deema Galambo ,&nbsp;Andreas Bergdahl","doi":"10.1016/j.crphys.2022.100097","DOIUrl":"10.1016/j.crphys.2022.100097","url":null,"abstract":"<div><p>Cardiolipin (CL) is a phospholipid molecule found in the inner mitochondrial membrane, where it normally associates with and activates the respiratory complexes. Following myocardial infarction, CL gets released from necrotic cells, consequently affecting neighboring tissues. We have previously demonstrated that physiological concentrations of up to 100 μM CL diminish endothelial cell migration and angiogenic sprouting. Since CL is vital to cellular life, we hypothesized that this molecule may have considerable implications on vascular smooth muscle cells bioenergetics, a key phase in atherogenesis. We examined the acute effects of physiological concentrations of CL on oxidative phosphorylation in permeabilized mice aorta using high-resolution respirometry and a substrate-inhibitor titration protocol. We found that CL significantly lowers LEAK and maximal State 3 respiration. In addition, we found that the acceptor control ratio, representing the coupling between oxidation and phosphorylation, was significantly upregulated by CL. Our findings demonstrate that <em>in situ</em> mitochondrial respiration in permeabilized smooth muscle cells is attenuated when physiological concentrations of CL are applied acutely. This could provide a novel therapy to reduce their dedifferentiation and consequently atherogenesis.</p></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"6 ","pages":"Article 100097"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b1/07/main.PMC9803913.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10474616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}