scholarly journals The natural compound TMYX reduces SAN cells rate by antagonizing the cAMP modulation of f-channels

2021 ◽  
Author(s):  
Chiara Piantoni ◽  
Manuel Paina ◽  
David Molla ◽  
Sheng Liu ◽  
Giorgia Bertoli ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Competitive Inhibition ◽  
Selective Reduction ◽  
Inhibition Mechanism ◽  
Metabolic Demand ◽  
Diastolic Phase ◽  
Pacemaker Channels ◽  
Spontaneous Action ◽  
Spontaneous Action Potentials

Tongmai Yangxin (TMYX), is a complex compound of a Traditional Chinese Medicine (TCM) used to treat several cardiac rhythm disorders; however, no information regarding its mechanism of action is available. In this study we provide a detailed characterization of the effects of TMYX on the electrical activity of pacemaker cells and unravel its mechanism of action. Single-cell electrophysiology revealed that TMYX elicits a reversible and dose-dependent (2/6 mg/ml) slowing of spontaneous action potentials rate (-20.8/-50.2%) by a selective reduction of the diastolic phase (-50.1/-76.0%). This action is mediated by a negative shift of the If activation curve (-6.7/-11.9 mV) and is caused by a reduction of the cAMP-induced stimulation of pacemaker channels. We provide evidence that TMYX acts by directly antagonizes the cAMP-induced allosteric modulation of the pacemaker channels. Noticeably, this mechanism functionally resembles the pharmacological actions of muscarinic stimulation or β-blockers, but it does not require generalized changes in cytoplasmic cAMP levels thus ensuring a selective action on rate. In agreement with a competitive inhibition mechanism, TMYX exerts its maximal antagonistic action at submaximal cAMP concentrations and then progressively becomes less effective thus ensuring a full contribution of If to pacemaker rate during high metabolic demand and sympathetic stimulation.

scholarly journals Id2 Represses Aldosterone-Stimulated Cardiac T-Type Calcium Channels Expression

2021 ◽  
Vol 22 (7) ◽  
pp. 3561
Author(s):  
Jumpei Ito ◽  
Tomomi Minemura ◽  
Sébastien Wälchli ◽  
Tomoaki Niimi ◽  
Yoshitaka Fujihara ◽  
...  
Keyword(s):  
Transcriptional Repressor ◽  
Neonatal Rat ◽  
Protective Mechanism ◽  
Pathological State ◽  
Rat Cardiomyocytes ◽  
Adult Mice ◽  
Spontaneous Action ◽  
Sirna Knockdown ◽  
Spontaneous Action Potentials ◽  
Ca2 Channels

Aldosterone excess is a cardiovascular risk factor. Aldosterone can directly stimulate an electrical remodeling of cardiomyocytes leading to cardiac arrhythmia and hypertrophy. L-type and T-type voltage-gated calcium (Ca2+) channels expression are increased by aldosterone in cardiomyocytes. To further understand the regulation of these channels expression, we studied the role of a transcriptional repressor, the inhibitor of differentiation/DNA binding protein 2 (Id2). We found that aldosterone inhibited the expression of Id2 in neonatal rat cardiomyocytes and in the heart of adult mice. When Id2 was overexpressed in cardiomyocytes, we observed a reduction in the spontaneous action potentials rate and an arrest in aldosterone-stimulated rate increase. Accordingly, Id2 siRNA knockdown increased this rate. We also observed that CaV1.2 (L-type Ca2+ channel) or CaV3.1, and CaV3.2 (T-type Ca2+ channels) mRNA expression levels and Ca2+ currents were affected by Id2 presence. These observations were further corroborated in a heart specific Id2- transgenic mice. Taken together, our results suggest that Id2 functions as a transcriptional repressor for L- and T-type Ca2+ channels, particularly CaV3.1, in cardiomyocytes and its expression is controlled by aldosterone. We propose that Id2 might contributes to a protective mechanism in cardiomyocytes preventing the presence of channels associated with a pathological state.

Study of Low-Grade Nickel Laterite Processing Using Palm Shell Charcoal as Reductant

2020 ◽  
Vol 1000 ◽  
pp. 436-446
Author(s):  
Bambang Suharno ◽  
Nolzha Primadha Ilman ◽  
Achmad Shofi ◽  
Deni Ferdian ◽  
Fajar Nurjaman
Keyword(s):  
Sodium Sulfate ◽  
Selective Reduction ◽  
Reduction Process ◽  
Low Grade ◽  
X Ray Diffraction ◽  
X Ray ◽  
Palm Shell ◽  
Higher Temperature ◽  
Nickel Grade

This study was conducted to investigate the effect of palm shell charcoal reductant in the selective reduction of nickel ore with the addition of additive at various temperatures and times. In this present work, 10 wt. % of sodium sulfate as additive and 5, 10, 15 wt. % of palm shell charcoal as reductants were used. The reduction of nickel ore was performed at 950oC, 1050oC, and 1150oC for 60, 90, and 120 minutes. A wet magnetic separation method was then carried out to separate the concentrates and tailings. Characterization of reduced ore was performed by X-Ray Diffraction (XRD) and Scanning Electron Microscope (SEM) with Energy Dispersive X-ray Spectroscopy (EDS), while the composition of ferronickel in concentrate was identified by X-Ray Fluorescence (XRF). The result showed that the higher temperature reduction, the higher of nickel grade, and its recovery at the concentrate. Nevertheless, the longer reduction time and the more reductant in nickel ore lowering the nickel grade and its recovery in the concentrate. The optimum condition in this selective reduction process was obtained with the addition of 5 wt. % of reductant and 10 wt. % of sodium sulfate in nickel ore, which was reduced at 1150oC for 60 minutes. It resulted in 4.60% and 73.23% for nickel grade and its recovery, respectively.

STUDIES ON ACTH-BINDING ANTIBODIES: CHARACTERIZATION OF IMMUNOLOGICAL SPECIFICITIES

1969 ◽  
Vol 62 (3) ◽  
pp. 521-536 ◽  
Author(s):  
M. L. Aubert ◽  
J.-P. Felber
Keyword(s):  
Binding Sites ◽  
Competitive Inhibition ◽  
Biologically Active ◽  
Active Part ◽  
Terminal Portion ◽  
Plasma Acth ◽  
Acth Fragments ◽  
Selection Of

ABSTRACT In investigations on the production and the specificity of anti-ACTH antibodies used for radioimmunoassay, differences have been observed between the various antibodies obtained. It was shown by means of competitive inhibition with different ACTH fragments that the binding of the ACTH molecule to its antibody can occur at different sites along the ACTH peptide. By varying the concentrations of the fragments and the conditions of the assays, it was possible to study the properties of each antibody. Thus antibodies which bind the N-terminal portion, or which exclusively bind the biologically active part of the ACTH chain (1–20), are the most suitable for radioimmunoassay. It was found, however, that the production of antiserum was generally more frequent when binding occurred to the C-terminal portion of the ACTH peptide. Should the presence of such fragments in plasma be confirmed, then the use of these antisera could lead to erroneous measurement of biologically inactive ACTH fragments. Thus, this study reveals that a selection of the antibody for specificity might be necessary for its application to the radioimmunoassay of plasma ACTH, and that this selection could be performed with the use of ACTH fragments. An approach to the problem of binding sites between antigen and antibody has been described and the possibility of introducing a radioimmunoassay for plasma ACTH fragments discussed.

Preparation and characterization of VO-ZSM5 catalyst for the selective reduction of NO with ammonia

2005 ◽  
Vol 59 (24-25) ◽  
pp. 2986-2989 ◽  
Author(s):  
A. Lavat ◽  
C.E. Quincoces ◽  
M.G. González
Keyword(s):  
Selective Reduction ◽  
Reduction Of No

Suppressor cells of the human NK activity: Characterization of the cells and mechanism of action

1983 ◽  
Vol 79 (2) ◽  
pp. 265-278 ◽  
Author(s):  
Jussi Tarkkanen ◽  
Eero Saksela ◽  
Eeva Von Willebrand ◽  
Eero Lehtonen
Keyword(s):  
Mechanism Of Action ◽  
Suppressor Cells ◽  
Nk Activity
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