bioRxiv - Physiology最新文献

{"title":"Session duration affects the magnitude of post-exercise hypervolemia but not the erythropoietin response to acute high-intensity interval exercise","authors":"Thomas R Tripp, Allison M Caswell, Brittany A Edgett, Martin J MacInnis","doi":"10.1101/2024.09.03.611105","DOIUrl":"https://doi.org/10.1101/2024.09.03.611105","url":null,"abstract":"The increase in plasma volume ~24 hours post-exercise may act as an erythropoietic signal, but this mechanism's responsiveness to different exercise prescription variables is poorly understood. The purpose of this study was to determine the impact of high-intensity interval exercise duration on plasma volume and related responses. On separate days, 16 healthy, recreationally active participants (n=8 males; n=8 females) performed four (4x4) or eight intervals (8x4) consisting of 4 min at 105% critical power with 3 min recovery. Venous blood samples collected before, immediately after, and 24 hours after each HIIT session were used to measure hemoglobin concentration and hematocrit to calculate plasma volume changes. Erythropoietic and plasma volume regulating hormone concentrations were measured using ELISA kits. Plasma volume decreased immediately after both protocols (4x4: -4.4\t±3.5%, p<0.05; 8x4: -4.4\t±3.6%, p<0.05) but was only significantly elevated above baseline 24 hours after the 8x4 protocol (4x4: +1.0\t±7.1%, p>0.05; 8x4: +5.6\t±4.6%, p<0.05). Erythropoietin concentration ([EPO]) was higher than baseline 24 hours after the HIIT protocols (4x4: Pre vs 24 h post: 6.5\t±3.1 vs. 7.1\t±3.3 mIU/mL; 8x4: 6.9\t±3.7 vs. 7.3\t±3.7 mIU/mL; main effect of time, p<0.05) with no difference between protocols (p>0.05). [Aldosterone] was elevated immediately post-exercise after both protocols (4x4: Pre vs 0 h post: 295\t±151 vs. 544\t±259 pg/mL; 8x4: 335\t±235 vs. 821\t±553 pg/mL), but the 8x4 protocol caused a larger increase (interaction effect, p<0.05). That post-exercise hypervolemia may be exercise duration-dependent but is not required for increases in circulating EPO has important implications for endurance training aiming to increase oxygen delivery to active tissues.","PeriodicalId":501557,"journal":{"name":"bioRxiv - Physiology","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197745","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":"Humidity as a zeitgeber for circadian entrainment of insect systems","authors":"Shyh-Chi Chen, Grace Goodhart, Daniel Eaton, Nathan Catlett, Tabitha Cady, Hannah Tran, Luke E. Lutz, Lyn Wang, Ella Girard, Jaida Savino, Jodi Perry, Liddy Hall, Amena Bidiwala, Emma Tarter, Joshua Tompkin, Nina Greene, Joshua Benoit","doi":"10.1101/2024.09.04.611265","DOIUrl":"https://doi.org/10.1101/2024.09.04.611265","url":null,"abstract":"Humidity levels, like light and temperature, fluctuate daily yet are less predictable; however, whether humidity entrains circadian clocks and enables animals to synchronize behaviors to environmental variations remains unknown. Here, we investigate the circadian humidity entrainment in various insects. Multiple species robustly respond to humidity cycles, and when the humidity cue is removed, their rhythmic behaviors continue, suggesting that humidity-associated rhythmic activities are under circadian control. Moreover, the Drosophila clock and hygrosensation mutants lack rhythmic activities during and after humidity entrainment, indicating that the core clock components and hygrosensors are essential to circadian entrainment. Our findings identify that humidity serves as a novel zeitgeber for circadian entrainment for insects that could have broad applicability and importance among animal systems.","PeriodicalId":501557,"journal":{"name":"bioRxiv - Physiology","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197759","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":"Altered cellular metabolic pathway and epithelial cell maturation induced by MYO5B defects are partially reversible by LPAR5 activation","authors":"Michael Momoh, Sudiksha Rathan-Kumar, Andreanna Burman, Monica E Brown, Francisca Adeniran, Cynthia Ramos, James R Goldenring, Joseph T Roland, Izumi Kaji","doi":"10.1101/2024.09.03.610579","DOIUrl":"https://doi.org/10.1101/2024.09.03.610579","url":null,"abstract":"Functional loss of the motor protein, Myosin Vb (MYO5B), induces various defects in intestinal epithelial function and causes a congenital diarrheal disorder, microvillus inclusion disease (MVID). Utilizing the MVID model mice, Vil1-CreERT2;Myo5bflox/flox (MYO5B∆IEC) and Vil1-CreERT2;Myo5bflox/G519R (MYO5B(G519R)), we previously reported that functional MYO5B loss disrupts progenitor cell differentiation and enterocyte maturation that result in villus blunting and deadly malabsorption symptoms. In this study, we determined that both absence and a point mutation of MYO5B impair lipid metabolism and alter mitochondrial structure, which may underlie the progenitor cell malfunction observed in MVID intestine. Along with a decrease in fatty acid oxidation, the lipogenesis pathway was enhanced in the MYO5B∆IEC small intestine. Consistent with these observations in vivo, RNA-sequencing of enteroids generated from two MVID mouse strains showed similar downregulation of energy metabolic enzymes, including mitochondrial oxidative phosphorylation genes. In our previous studies, lysophosphatidic acid (LPA) signaling ameliorates epithelial cell defects in MYO5B∆IEC tissues and enteroids. The present study demonstrates that the highly soluble LPAR5-preferred agonist, Compound-1, improved sodium transporter localization and absorptive function, and tuft cell differentiation in patient-modeled MVID animals that carry independent mutations in MYO5B. Body weight loss in male MYO5B(G519R) mice was ameliorated by Compound-1. These observations suggest that Compound-1 treatment has a trophic effect on intestine with MYO5B functional loss through epithelial cell-autonomous pathways that may improve the differentiation of progenitor cells and the maturation of enterocytes. Targeting LPAR5 may represent an effective therapeutic approach for treatment of MVID symptoms induced by different point mutations in MYO5B.","PeriodicalId":501557,"journal":{"name":"bioRxiv - Physiology","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197746","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":"Genome composition predicts physiological response to environmental change in polyploid salamanders","authors":"Isabella Burger, Michael Itgen, Lynn Tan, Parker Woodward, Linet Rivas, Tamyra Hunt, Hailey Ready, Xochitl Martin Geronimo, Robert Denton, Eric Riddell","doi":"10.1101/2024.09.06.611688","DOIUrl":"https://doi.org/10.1101/2024.09.06.611688","url":null,"abstract":"Multi-trait analyses can be used to measure the differential performance of phenotypic traits in species complexes. Hybridization within these complexes can result in a mismatch between mitochondrial and nuclear DNA that may lead to reduced performance and acclimation capacity in hybrids. To test the effect of this mismatch on physiology, we compared physiological performance and acclimation capacity of metabolic rate (VCO2) and total resistance to water loss (rT) between two sexual Ambystoma species and a closely related unisexual lineage. We also separated unisexuals by their unique biotypes to determine how physiology varies with subgenomic composition. We found that unisexual biotypes exhibited phenotypes more like their related sexual species than to other unisexuals. We also found a trade-off between rT and VCO2, with increasing rT resulting in a decrease in VCO2. This trade-off was stronger in unisexuals than either sexual species, indicating that unisexuals may be more sensitive to environmental change. While we did not find evidence for mitonuclear mismatch, our results show that genomic composition of hybrids is more indicative of trait performance than other metrics (e.g., ploidy). Multi-trait analyses are imperative for understanding variation in phenotypic diversity, providing insight into how this diversity affects species responses to environmental change.","PeriodicalId":501557,"journal":{"name":"bioRxiv - Physiology","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197747","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":"Computational Study of the Excitation of Human Induced Pluripotent Stem-Cell Derived Cardiomyocytes","authors":"Roshni Shetty, Raffi Samurkashian, Leslie Tung","doi":"10.1101/2024.09.03.611054","DOIUrl":"https://doi.org/10.1101/2024.09.03.611054","url":null,"abstract":"Human induced pluripotent stem-cell derived cardiomyocytes (hiPSC-CMs) have proven to be a revolutionary advance for tissue engineering, disease modeling, and drug testing and discovery. Computational modeling enables a detailed electrophysiological analysis that is otherwise difficult or impossible to achieve under strictly experimental settings. Action potential characteristics of hiPSC-CMs measured in our lab at four different pacing rates were used it to modify the computational Kernik-Clancy hiPSC-CM model. The modified model was used to compare the excitation of single hiPSC-CMs with that of single human ventricular cardiomyocytes (hV-CMs) under varying conditions, including at stimulation at different strengths, rates and pulse durations. The physiological stimulation of both hiPSC-CMs and hV-CMs embedded within a tissue strand involves a biphasic waveform during which time excitatory currents (particularly INa, but also ICaT and ICaL for hiPSC-CMs and INaL and ICaL for hV-CMs) are activated during both phases of the waveform. INa in particular activated more slowly and with diminished amplitude under conditions of increasing pacing rate or increasing intracellular resistance. Lastly, histograms characterizing the relative amounts of excitatory currents in a population of hiPSC-CMs become broader with increasing levels of INa block, with ICaT and ICaL working in tandem to excite cells where INa has failed to activate. In general, hiPSC-CMs were found to be more excitable from rest compared with hV-CMs owing to their more depolarized resting potential and intrinsic automaticity despite a lower sodium channel density. Such a mismatch should be taken into consideration for applications using these cells, particularly for cardiac repair.","PeriodicalId":501557,"journal":{"name":"bioRxiv - Physiology","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197753","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":"Estimating soil mineral nitrogen from data-sparse field experiments using crop model-guided machine learning approach","authors":"Rishabh Gupta, Satya Krishna Pothapragada, Weihuang Xu, Prateek Kumar Goel, Miguel Barrera, Mira Saldanha, Joel Harley, Kelly T. Morgan, Alina Zare, Lincoln Zotarelli","doi":"10.1101/2024.09.03.610387","DOIUrl":"https://doi.org/10.1101/2024.09.03.610387","url":null,"abstract":"Sandy soils are susceptible to excessive nitrogen (N) leaching under intensive crop production which is linked with the soil's low nutrient holding capacity and high-water infiltration rate. Estimating soil mineral nitrogen (SMN) at the daily time-step is crucial in providing fertilizer recommendations balancing plant nitrogen use efficiency (NUE) and N losses to the environment. Crop models [e.g., Decision Support System for Agrotechnology Transfer (DSSAT)] can simulate the trend of SMN in varied fertilizer rates and timing of application but are unable to replicate its magnitude due to the inability to capture high-water table conditions in a sub-irrigated soil. As an alternative to such physics-based model, time-series deep learning (DL) models based on a long short-term memory (LSTM) are promising in understanding nonlinearity among complex variables. Yet, purely data-driven DL models for crops are difficult to obtain due to the insufficient amount of data available and the excessive costs with producing more data. To address this challenge, a hybrid model (hybrid-LSTM) was developed by leveraging both the DSSAT andLSTM models to estimate daily SMN primarily using daily weather, applied fertilizer rates- timings, and the SMN sparse observations. This study used the observations from field trials conducted between 2010-2014 in Hastings, FL. The first step was to calibrate the DSSAT-SUBSTOR-Potato model to produce reliable SMN of the topsoil for treatments with varied N applied fertilizer rates split among the pre-planting, emergence, and tuber-initiation stages of the potato crop. Thereafter, the hybrid-LSTM model was trained on the calibrated DSSAT simulated SMN time-series and fine-tuned its predictions using the observed SMN to improve DSSAT simulated SMN. The hybrid-LSTM model was then tested on both calibrated and uncalibrated DSSAT SMN simulations where it outperformed the DSSAT model (range of improvement ranged ~18-30% on comparing the normalized root mean squared error) in providing reliable estimates of SMN across most of the farms and years. This novel hybrid modeling approach could guide stakeholders and farmers to build sustainable N management with improved crop NUE and yield and help in minimizing environmental losses.","PeriodicalId":501557,"journal":{"name":"bioRxiv - Physiology","volume":"99 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197754","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":"Selective Agonism of Liver and Gut FXR Prevents Cholestasis and Intestinal Atrophy in Parenterally Fed Neonatal Pigs","authors":"Yanjun Jiang, Zhengfeng Fang, Gregory Guthrie, Barbara Stoll, Shaji Chacko, Sen Lin, Bolette Hartmann, Jens J Holst, Harry Dawson, Jose J Pastor, Ignacio R Ipharraguerre, Douglas G Burrin","doi":"10.1101/2024.09.03.611073","DOIUrl":"https://doi.org/10.1101/2024.09.03.611073","url":null,"abstract":"BACKGROUND & AIMS: We aimed to investigate the relative efficacy of feeding different bile acids in preventing PNALD in neonatal pigs. METHODS: Newborn pigs given total parenteral nutrition (TPN) combined with minimal enteral feeding of chenodeoxycholic acid (CDCA), or increasing doses of obeticholic acid (OCA) for 19 days. RESULTS: Enteral OCA (5 and 15 mg/kg), but not CDCA (30 mg/kg) reduced blood cholestasis markers compared to TPN controls and increased bile acids in the gallbladder and intestine. Major bile acids in the liver and distal intestine were CDCA, HCA, HDCA and OCA, and their relative proportions were increased by the type of bile acid (CDCA or OCA) given enterally. High doses of OCA increased the total NR1H4-agonistic bile acid profile in the liver and intestine above 50% total bile acids. Both CDCA and OCA treatments suppressed hepatic cyp7a1 expression, but only OCA increased hepatobiliary transporters, ABCB11, ABCC$ and ABCB1. Plasma phytosterol levels were reduced and biliary levels were increased by CDCA and OCA and hepatic sterol transporters, abcg5/8, expression were increased by OCA. Both CDCA and OCA increased plasma FGF19 and OCA increased intestinal FGF19, FABP6, and SLC51A. Both CDCA and OCA increased intestinal mucosal growth, whereas CDCA increased the plasma GLP-2, GLP-1 and GIP. CONCLUSIONS: Enteral OCA prevented cholestasis and phytosterolemia by increased hepatic bile acid and sterol transport via induction of hepatobiliary transporter FXR target genes and not by suppression of bile acid synthesis genes. We also showed an intestinal trophic action of OCA that demonstrates a dual clinical benefit of FXR agonism in the prevention of PNALD in piglets.","PeriodicalId":501557,"journal":{"name":"bioRxiv - Physiology","volume":"262 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197752","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":"Diet-induced hyperplastic expansion in subcutaneous adipose tissue and protection against adipose progenitor exhaustion in female mice are lost with ovariectomy.","authors":"Taylor B Scheidl, Jessica L Wager, Jennifer Thompson","doi":"10.1101/2024.09.05.611480","DOIUrl":"https://doi.org/10.1101/2024.09.05.611480","url":null,"abstract":"Background: The protection of females against cardiometabolic disease is in part attributable to a tendency for fat accumulation in subcutaneous depots, which promote lipid homeostasis by serving as a metabolic sink. At menopause this protection is lost, and body fat distribution resembles the male-like pattern of visceral adiposity. Adipose progenitor cells (APCs) can be recruited to support adipose expansion in the setting of obesity. Sex differences in diet-induced APC responses may in part explain sexual dimorphism in risk for obesity-associated insulin resistance; however, the role of sex and estrogen in governing APC function remains unclear. Methods: Four groups of C57BL/6 mice were assessed: intact males vs. females, and sham vs. ovariectomized (ovx) with or without estradiol (E2). Adipogenesis was stimulated by rosiglitazone (rosi), while obesity was induced by high fat/fructose diet (HHFD). Flow cytometry quantified the total number of APCs and identify committed preadipocytes by the loss of CD24 expression. Body composition was measured by NMR, while adipose function assessed by measuring circulating adipokines and free fatty acids and lipolysis in adipose explants. Results: Despite greater accumulation of fat mass in response to rosi, females were protected against the depletion in subcutaneous APCs and preadipocytes that was observed in rosi-treated males. Similar to intact males, APC and preadipocytes in subcutaneous depots of ovx females were reduced after rosi treatment. The protection of obese females against the development of insulin resistance and adipose dysfunction was lost with ovx, and E2 re-supplementation rescued HFFD-induced APC exhaustion. Exposure to HFFD after discontinuation of rosi exacerbated glucose intolerance in males only. Conclusions: Estrogen-mediated hyperplastic expansion in subcutaneous depots permits renewal of the APC pool and preservation of adipose function.","PeriodicalId":501557,"journal":{"name":"bioRxiv - Physiology","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197756","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":"Identification of leptolin as a novel anti-obesity adipokine","authors":"Jiarui Liu, Bingwei Wang, Zhijie Su, Xiaoxu Han, Miao He, Yun Zhao, Yujia Hou, Daotong Li, Weiguang Zhang, Lihua Qin, Ke Wang, Yanchun Li, Yi Yan, Siwang Yu, Xiaoshuai Huang, Tairan Yuwen, Ruimao Zheng","doi":"10.1101/2024.09.03.610963","DOIUrl":"https://doi.org/10.1101/2024.09.03.610963","url":null,"abstract":"Adipokines are key factors in regulating energy homeostasis. We identified a novel adipokine; we named it Leptolin. In humans, leptolin levels in white adipose tissue were positively corrected with exercise, and negatively associated with body mass index. Leptolin levels were positively correlated with lipolysis-promoting gene expression. Elevated leptolin in plasma of athletes, whereas lowered leptolin in plasma of obese individuals were observed. Leptolin gene-knockout mice exhibited increased adiposity and body weight, and decreased energy expenditure. Leptolin gene-overexpression mice showed obesity-resistant phenotypes.Treatment with leptolin promoted fat mobilization and energy expenditure, and reduced body weight, without affecting food-intake and motor activity. Together, leptolin, a novel adipokine with a capacity to improve metabolic status, may serve as a new therapeutic agent for obesity and metabolic disorders.","PeriodicalId":501557,"journal":{"name":"bioRxiv - Physiology","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197758","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":"Differential effects of obesity and diabetes on the action potential waveform and inward currents in rat ventricular myocytes.","authors":"Anatoliy Shmygol, Gilles Bru Mercier, Ahmed Sultan, Frank Christopher Howarth","doi":"10.1101/2024.09.03.610949","DOIUrl":"https://doi.org/10.1101/2024.09.03.610949","url":null,"abstract":"Obesity is a significant health concern worldwide, increasing the risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease. Studies have found various vascular anomalies, abnormal heart rhythm, and impaired electro-mechanical coupling in patients with diabetes. Research on non-diabetic obese individuals has shown that besides diabetes-related complications, obesity itself raises the risk of developing cardiovascular disease. Recent studies have revealed a decrease in the speed of electrical signal conduction in the heart, along with slight gap junction dysfunction, which is insufficient to explain the observed impediment of impulse conduction. It's still unclear whether this impairment is due to obesity-related fat toxicity or diabetes-related factors. Our study aimed to investigate the ventricular action potential parameters and voltage-gated Na+ (INa) and Ca2+ (I(Ca, L)) currents in Zucker fatty (ZF) rats in comparison to Zucker diabetic fatty (ZDF) rats, a well-established model of obesity and T2DM. Ventricular myocytes were enzymatically isolated from 25-30-week-old Zucker rats. Resting and action potentials were recorded from isolated left ventricular myocytes using a beta-escin perforated patch clamp in current-clamp mode; INa and I(Ca, L) were recorded using whole-cell patch clamp techniques. Ventricular myocytes from ZF rats showed higher excitability and faster upstroke velocity. ZF rats also had a larger density of INa. Conversely, ZDF rats had decreased INa which correlated with a reduced velocity of the action potential upstroke. There were no changes in the density or voltage sensitivity of I(Ca, L) among the three groups of animals.\u0000In conclusion, obesity alone and obesity accompanied by DM have distinct effects on the action potential waveform, INa density and excitability of ventricular myocytes in a rat model of T2DM.","PeriodicalId":501557,"journal":{"name":"bioRxiv - Physiology","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197760","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}