Pulsed magnetic stimulation modifies amplitude of action potentials in vitro via ionic channels-dependent mechanism

2015 ◽  
Vol 36 (5) ◽  
pp. 386-397 ◽  
Author(s):  
Zaghloul Ahmed ◽  
Andrzej Wieraszko
Keyword(s):  
Action Potentials ◽  
Magnetic Stimulation ◽  
Ionic Channels ◽  
Dependent Mechanism

scholarly journals Assessing the utility of MAGNETO to control neuronal excitability in the somatosensory cortex

2019 ◽  
Author(s):  
Koen Kole ◽  
Yiping Zhang ◽  
Eric J. R. Jansen ◽  
Terence Brouns ◽  
Ate Bijlsma ◽  
...  
Keyword(s):  
Somatosensory Cortex ◽  
Action Potentials ◽  
Magnetic Stimulation ◽  
Neuronal Excitability ◽  
Neural Interfaces ◽  
Intracellular Recordings ◽  
Membrane Excitability ◽  
Freely Moving ◽  
The Brain

Magnetic neuromodulation has outstanding promise for the development of novel neural interfaces without direct physical intervention with the brain. Here we tested the utility of Magneto in the adult somatosensory cortex by performing whole-cell intracellular recordings in vitro and extracellular recordings in freely moving mice. Results show that magnetic stimulation does not alter subthreshold membrane excitability or contribute to the generation of action potentials in virally transduced neurons expressing Magneto.

Stretch of mammalian nerve in vitro: Effect on compound action potentials

2000 ◽  
Vol 5 (4) ◽  
pp. 227-235 ◽  
Author(s):  
Sidney Ochs ◽  
Rahman Pourmand ◽  
Kenan Si ◽  
Richard N. Friedman
Keyword(s):  
Action Potentials ◽  
Compound Action Potentials ◽  
Vitro Effect ◽  
Mammalian Nerve ◽  
Compound Action

scholarly journals Extracellular detection of neuronal coupling

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Elmer Guzman ◽  
Zhuowei Cheng ◽  
Paul K. Hansma ◽  
Kenneth R. Tovar ◽  
Linda R. Petzold ◽  
...  
Keyword(s):  
Action Potentials ◽  
Microelectrode Arrays ◽  
Short Latency ◽  
Spike Sorting ◽  
Neuronal Connectivity ◽  
Direct Stimulation ◽  
Multiple Electrodes

AbstractWe developed a method to non-invasively detect synaptic relationships among neurons from in vitro networks. Our method uses microelectrode arrays on which neurons are cultured and from which propagation of extracellular action potentials (eAPs) in single axons are recorded at multiple electrodes. Detecting eAP propagation bypasses ambiguity introduced by spike sorting. Our methods identify short latency spiking relationships between neurons with properties expected of synaptically coupled neurons, namely they were recapitulated by direct stimulation and were sensitive to changing the number of active synaptic sites. Our methods enabled us to assemble a functional subset of neuronal connectivity in our cultures.

scholarly journals A predictive in vitro risk assessment platform for pro-arrhythmic toxicity using human 3D cardiac microtissues

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Celinda M. Kofron ◽  
Tae Yun Kim ◽  
Fabiola Munarin ◽  
Arvin H. Soepriatna ◽  
Rajeev J. Kant ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Action Potentials ◽  
Induced Pluripotent Stem Cell ◽  
Human Action ◽  
Environmental Toxicants ◽  
Pharmaceutical Drugs ◽  
Industrial Chemicals ◽  
Endocrine Disrupting Chemical

AbstractCardiotoxicity of pharmaceutical drugs, industrial chemicals, and environmental toxicants can be severe, even life threatening, which necessitates a thorough evaluation of the human response to chemical compounds. Predicting risks for arrhythmia and sudden cardiac death accurately is critical for defining safety profiles. Currently available approaches have limitations including a focus on single select ion channels, the use of non-human species in vitro and in vivo, and limited direct physiological translation. We have advanced the robustness and reproducibility of in vitro platforms for assessing pro-arrhythmic cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes and human cardiac fibroblasts in 3-dimensional microtissues. Using automated algorithms and statistical analyses of eight comprehensive evaluation metrics of cardiac action potentials, we demonstrate that tissue-engineered human cardiac microtissues respond appropriately to physiological stimuli and effectively differentiate between high-risk and low-risk compounds exhibiting blockade of the hERG channel (E4031 and ranolazine, respectively). Further, we show that the environmental endocrine disrupting chemical bisphenol-A (BPA) causes acute and sensitive disruption of human action potentials in the nanomolar range. Thus, this novel human 3D in vitro pro-arrhythmic risk assessment platform addresses critical needs in cardiotoxicity testing for both environmental and pharmaceutical compounds and can be leveraged to establish safe human exposure levels.

scholarly journals The EBV-Encoded Oncoprotein, LMP1, Recruits and Transforms Fibroblasts via an ERK-MAPK-Dependent Mechanism

Pathogens ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 982
Author(s):  
Alexandra M Davis ◽  
Abigail Rapley ◽  
Christopher W Dawson ◽  
Lawrence S Young ◽  
Mhairi A Morris
Keyword(s):  
Tumour Microenvironment ◽  
Barr Virus ◽  
Erk Mapk ◽  
Lmp1 Expression ◽  
Epstein Barr ◽  
Similar Vein ◽  
Oncogenic Protein ◽  
Intense Debate ◽  
Dependent Mechanism

Latent membrane protein 1 (LMP1), the major oncoprotein encoded by Epstein–Barr virus (EBV), is expressed at widely variable levels in undifferentiated nasopharyngeal carcinoma (NPC) biopsies, fueling intense debate in the field as to the importance of this oncogenic protein in disease pathogenesis. LMP1-positive NPCs are reportedly more aggressive, and in a similar vein, the presence of cancer-associated fibroblasts (CAFs) surrounding “nests” of tumour cells in NPC serve as indicators of poor prognosis. However, there is currently no evidence linking LMP1 expression and the presence of CAFs in NPC. In this study, we demonstrate the ability of LMP1 to recruit fibroblasts in vitro in an ERK-MAPK-dependent mechanism, along with enhanced viability, invasiveness and transformation to a myofibroblast-like phenotype. Taken together, these findings support a putative role for LMP1 in recruiting CAFs to the tumour microenvironment in NPC, ultimately contributing to metastatic disease.

scholarly journals PAR-4/Ca2+-calpain pathway activation stimulates platelet-derived microparticles in hyperglycemic type 2 diabetes

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Alessandra Giannella ◽  
Giulio Ceolotto ◽  
Claudia Maria Radu ◽  
Arianna Cattelan ◽  
Elisabetta Iori ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Normal Glucose Tolerance ◽  
Calpain Inhibitor ◽  
Pathway Activation ◽  
Normal Glucose ◽  
Circulating Levels ◽  
Dependent Mechanism

Abstract Background Patients with type 2 diabetes (T2DM) have a prothrombotic state that needs to be fully clarified; microparticles (MPs) have emerged as mediators and markers of this condition. Thus, we investigate, in vivo, in T2DM either with good (HbA1c ≤ 7.0%; GGC) or poor (HbA1c > 7.0%; PGC) glycemic control, the circulating levels of MPs, and in vitro, the molecular pathways involved in the release of MPs from platelets (PMP) and tested their pro-inflammatory effects on THP-1 transformed macrophages. Methods In 59 T2DM, and 23 control subjects with normal glucose tolerance (NGT), circulating levels of CD62E+, CD62P+, CD142+, CD45+ MPs were determined by flow cytometry, while plasma levels of ICAM-1, VCAM-1, IL-6 by ELISA. In vitro, PMP release and activation of isolated platelets from GGC and PGC were investigated, along with their effect on IL-6 secretion in THP-1 transformed macrophages. Results We found that MPs CD62P+ (PMP) and CD142+ (tissue factor-bearing MP) were significantly higher in PGC T2DM than GGC T2DM and NGT. Among MPs, PMP were also correlated with HbA1c and IL-6. In vitro, we showed that acute thrombin exposure stimulated a significantly higher PMP release in PGC T2DM than GGC T2DM through a more robust activation of PAR-4 receptor than PAR-1 receptor. Treatment with PAR-4 agonist induced an increased release of PMP in PGC with a Ca2+-calpain dependent mechanism since this effect was blunted by calpain inhibitor. Finally, the uptake of PMP derived from PAR-4 treated PGC platelets into THP-1 transformed macrophages promoted a marked increase of IL-6 release compared to PMP derived from GGC through the activation of the NF-kB pathway. Conclusions These results identify PAR-4 as a mediator of platelet activation, microparticle release, and inflammation, in poorly controlled T2DM.

scholarly journals Spleen Tyrosine Kinase Inhibition Modulates p53 Activity

2017 ◽  
Vol 10 ◽  
pp. 117906601773156 ◽  
Author(s):  
Mohammad Althubiti
Keyword(s):  
Tyrosine Kinase ◽  
Survival Rates ◽  
Lymphocytic Leukemia ◽  
Spleen Tyrosine Kinase ◽  
Ht1080 Cell ◽  
P53 Expression ◽  
Chemical Inhibitors ◽  
Dependent Mechanism

Spleen tyrosine kinase (SYK) is a cytoplasmic enzyme that promotes survival and proliferation of B cells. SYK inhibition has shown promising results in the treatment of arthritis and chronic lymphocytic leukemia (CLL). However, in other context, it has been shown that SYK overexpression in epithelial cancer cells induced senescence in p53-dependent mechanism, which underscored its antineoplastic activity in vitro. Here, we show that SYK was induced in response of DNA damage in parallel with p53 levels. In addition, using chemical inhibitors of SYK reduced p53 levels in HCT116 and HT1080 cell lines, which underlines the role of SYK inhibition on p53 activity. Furthermore, SYK inhibition modulated the cell growth, which resulted in a decreasing in cell death. Interestingly, SYK expression showed a positive prognosis in patients with solid tumors in correlations with their survival rates, as expected negative correlation was seen between SYK expression and survival rate of patients with CLL. In conclusion, these findings demonstrate that SYK inhibition modulates p53 expression and activity in HCT116 and HT1080 cells. Reconsidering using of SYK inhibitors in clinical setting in the future should be evaluated carefully in accordance with these findings to prevent the formation of secondary malignancies.

scholarly journals Synaptically triggered action potentials begin as a depolarizing ramp in rat hippocampal neurones in vitro.

1992 ◽  
Vol 453 (1) ◽  
pp. 663-687 ◽  
Author(s):  
G Y Hu ◽  
O Hvalby ◽  
J C Lacaille ◽  
B Piercey ◽  
T Ostberg ◽  
...  
Keyword(s):  
Action Potentials

Effect of Heparin on TAFI-Dependent Inhibition of Fibrinolysis: Relative Importance of TAFIa Generated by Clot-Bound and Fluid Phase Thrombin

2002 ◽  
Vol 88 (08) ◽  
pp. 282-287 ◽  
Author(s):  
Anna Pentimone ◽  
Bianca Binetti ◽  
Marialisa Cramarossa ◽  
Donatella Piro ◽  
Nicola Semeraro ◽  
...  
Keyword(s):  
Thrombin Generation ◽  
Blood Clot ◽  
Fluid Phase ◽  
Clot Lysis ◽  
Relative Importance ◽  
Thrombin Activatable Fibrinolysis Inhibitor ◽  
Dependent Inhibition ◽  
Fibrinolysis Inhibitor ◽  
Dependent Mechanism

SummaryHeparin has been proposed to enhance thrombolysis by inhibiting thrombin-dependent generation of activated TAFI (thrombin activatable fibrinolysis inhibitor), a carboxypeptidase that inhibits fibrinolysis. We evaluated the effect of heparin in an in vitro thrombolysis model consisting of a radiolabelled blood clot submerged in defibrinated plasma. Fibrinolysis was induced by adding t-PA (250 ng/ml) and calcium to the plasma bath. Control experiments indicated that thrombin generation induced by recalcification caused significant TAFI activation and inhibited clot lysis. Heparin (up to 1 U/ml), added to the plasma bath, failed to enhance clot lysis. Thrombin generation in the fluid phase was totally inhibited by heparin at concentrations > 0.5 U/ml. In contrast, thrombin generation on the clot surface was not inhibited by heparin (1 U/ml). TAFIa generation did occur in heparin-containing samples (1 U/ml) and amounted to about 10% of TAFIa formed in control samples. This low amount of TAFIa did exert antifibrinolytic activity as indicated by the observation that the addition of a specific TAFIa inhibitor (PTI) along with heparin enhanced clot lysis. Hirudin (10 µg/ml), at variance with heparin, inhibited clot-bound thrombin and enhanced clot lysis. These data show that heparin is unable to stimulate fibrinolysis through a TAFI-dependent mechanism, most likely because of its inefficiency in inhibiting thrombin generation on the clot surface. Moreover, they suggest that clot-bound thrombin plays a major role in TAFI-mediated inhibition of fibrinolysis through “localized” TAFIa generation.

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