Mechanistic Pathways of ATP Sensitive Potassium Channels Referring to Cardio-Protective Effects and Cellular Functions

AbstractA study of potassium channels correlates the fundamentals of mechanistic pathways and various physiological functions. The knowledge of these pathways provides the background, how to determine unit cell functions and to affect cardio protection. ATP sensitive potassium channels adjust excitability of membrane and functions as per metabolic status of cell. A lot of energy consumption primarily occurred in skeletal muscles which also express high number of potassium channels. The increase in calcium release and high heat production is occurred due to loss of potassium channels. Such type of mediations determines metabolic changes and energy required in the dissipation. IPC reduces infarct size in anesthetized mice. In ischemic-reperfusion, pressure in left ventricle was watched while contractile power recovery did not happen. It was seen that elements of intact potassium channel are fundamental for Ischemic preconditioning (IPC). If more prominent is enactment of potassium channels and their cardiologic effects create high heart rate. All the more as of late, it has been suggested that mitochondrial ATP sensitive potassium channels are critical as closing stage effectors which trigger IPC as opposed to sarcolemmal potassium channels. Nevertheless, the importance of the potassium channels reconsidered in cardio-protection in present findings. These discoveries recommend that potassium channels in the adjusting ischemic-reperfusion damage in mice. The heart rate of the mouse occurred during ischemia; enhance watchful extrapolation applied to larger warm blooded animals.

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Multimode light microscopy and fluorescence-based reagents as tools for the study of chemical and molecular dynamics of living cells and tissues

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100122496 ◽

1992 ◽

Vol 50 (1) ◽

pp. 418-419

Author(s):

D. L. Taylor

Keyword(s):

Living Cells ◽

Cellular Level ◽

Molecular Techniques ◽

Cellular Functions ◽

Macromolecular Assemblies ◽

Cell Functions ◽

Molecular Events ◽

Yield Information ◽

Full Knowledge ◽

Structural Methods

Cells function through the complex temporal and spatial interplay of ions, metabolites, macromolecules and macromolecular assemblies. Biochemical approaches allow the investigator to define the components and the solution chemical reactions that might be involved in cellular functions. Static structural methods can yield information concerning the 2- and 3-D organization of known and unknown cellular constituents. Genetic and molecular techniques are powerful approaches that can alter specific functions through the manipulation of gene products and thus identify necessary components and sequences of molecular events. However, full knowledge of the mechanism of particular cell functions will require direct measurement of the interplay of cellular constituents. Therefore, there has been a need to develop methods that can yield chemical and molecular information in time and space in living cells, while allowing the integration of information from biochemical, molecular and genetic approaches at the cellular level.

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Role of Heart Rate Reduction in the Management of Myocarditis

Current Pharmaceutical Design ◽

10.2174/1381612824666180111105923 ◽

2018 ◽

Vol 24 (3) ◽

pp. 365-378 ◽

Cited By ~ 2

Author(s):

Chen Guang-Yi ◽

Ge Li-Sha ◽

Li Yue-Chun

Keyword(s):

Heart Rate ◽

Nitrosative Stress ◽

Ventricular Remodeling ◽

Animal Experiments ◽

Viral Myocarditis ◽

Protective Effects ◽

Heart Rate Reduction ◽

Rate Reduction ◽

Beneficial Effects ◽

Biological Technique

The morbidity of myocarditis demonstrates an upward tendency by years, is commonly defined as the inflammation of myocytes and is caused by multiple factors. With the development of the molecular biological technique, great breakthroughs in the diagnosis and understanding of pathophysiological mechanisms of myocarditis have recently been achieved. Several questions remain unresolved, however, including standard treatment approaches to myocarditis, which remain controversial and ambiguous. Heart rate, as an independent risk factor, has been shown to be related to cardiac disease. Recent studies also show that the autonomic nervous system is involved in immunomodulatory myocarditis processes. Heart rate reduction treatment is recommended in myocarditis based on a number of animal experiments and clinical trials. It is possible that heart rate-lowering treatments can help to attenuate the inflammatory response and myocyte injury and reverse ventricular remodeling. However, how to execute the protective effects of heart rate reduction on myocarditis is still not clear. In this review, we discuss the pathogenesis and pathophysiological process of viral myocarditis and propose heart rate lowering as a therapeutic target for myocarditis, especially in light of the third-generation β-blockade carvedilol and funny channel blocker ivabradine. We also highlight some additional beneficial effects of such heart rate reduction agents, including anti-inflammatory, antioxidation, anti-nitrosative stress, anti-fibrosis and antiapoptosis properties.

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Modulating Tumor Cell Functions by Tunable Nanopatterned Ligand Presentation

Nanomaterials ◽

10.3390/nano10020212 ◽

2020 ◽

Vol 10 (2) ◽

pp. 212

Author(s):

Katharina Amschler ◽

Michael P. Schön

Keyword(s):

Extracellular Matrix ◽

Tumor Cell ◽

Cell Fate ◽

Epithelial Mesenchymal Transition ◽

Model Systems ◽

Cellular Functions ◽

Biophysical Parameters ◽

Ligand Density ◽

Mesenchymal Transition ◽

Cell Functions

Cancer comprises a large group of complex diseases which arise from the misrouted interplay of mutated cells with other cells and the extracellular matrix. The extracellular matrix is a highly dynamic structure providing biochemical and biophysical cues that regulate tumor cell behavior. While the relevance of biochemical signals has been appreciated, the complex input of biophysical properties like the variation of ligand density and distribution is a relatively new field in cancer research. Nanotechnology has become a very promising tool to mimic the physiological dimension of biophysical signals and their positive (i.e., growth-promoting) and negative (i.e., anti-tumoral or cytotoxic) effects on cellular functions. Here, we review tumor-associated cellular functions such as proliferation, epithelial-mesenchymal transition (EMT), invasion, and phenotype switch that are regulated by biophysical parameters such as ligand density or substrate elasticity. We also address the question of how such factors exert inhibitory or even toxic effects upon tumor cells. We describe three principles of nanostructured model systems based on block copolymer nanolithography, electron beam lithography, and DNA origami that have contributed to our understanding of how biophysical signals direct cancer cell fate.

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Thermodynamics of ion binding and occupancy in potassium channels

Chemical Science ◽

10.1039/d1sc01887f ◽

2021 ◽

Author(s):

Zhifeng Jing ◽

Joshua A. Rackers ◽

Lawrence Pratt ◽

Chengwen Liu ◽

Susan B. Rempe ◽

...

Keyword(s):

Potassium Channels ◽

Ion Binding ◽

Cellular Functions ◽

Ion Conduction

Potassium channels modulate various cellular functions through efficient and selective conduction of K+ ions. The mechanism of ion conduction in potassium channels has recently emerged as a topic of debate....

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Effect of heart rate on left ventricular longitudinal myocardial function in type 2 diabetes mellitus

Cardiovascular Diabetology ◽

10.1186/s12933-021-01278-7 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Yuki Yamauchi ◽

Hidekazu Tanaka ◽

Shun Yokota ◽

Yasuhide Mochizuki ◽

Yuko Yoshigai ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Heart Rate ◽

Type 2 Diabetes Mellitus ◽

Myocardial Function ◽

Normal Subjects ◽

Left Ventricular ◽

High Heart Rate ◽

Lv Dysfunction

Abstract Background Left ventricular (LV) longitudinal myocardial dysfunction is considered a marker of preclinical LV dysfunction in patients with type 2 diabetes mellitus (T2DM). High heart rate (HR) is associated with cardiovascular outcomes, but the effect of HR on LV longitudinal myocardial function in T2DM patients is uncertain. Methods We studied 192 T2DM patients with preserved LV ejection fraction (LVEF), and 81 age-, sex-, and LVEF-matched healthy volunteers. HR was measured as the average HR during echocardiography, and high HR was defined as resting HR ≥ 70 beats/minute. LV longitudinal myocardial function was assessed as global longitudinal strain (GLS). The predefined cutoff for subclinical LV dysfunction was set at GLS < 18%. Results GLS in T2DM patients with high HR was significantly lower than that in T2DM patients with low HR (16.3% ± 4.2% vs. 17.8% ± 2.8%; P = 0.03), whereas GLS in normal subjects with high and low HR was similar (20.3 ± 1.7% vs. 20.3 ± 2.0%; P = 0.99). Multivariable logistic regression analysis showed that high HR (odds ratio: 1.04; 95% confidence interval: 1.01–1.07; P = 0.01) was independently associated with GLS < 18% in T2DM patients as well as HbA1c, T2DM duration, LVEF, body mass index, and mitral inflow E and mitral e’ annular velocity ratio. One sequential logistic model evaluating the associations between GLS < 18% and clinical variables in T2DM patients showed an improvement with the addition of LVEF and E/e’ (P < 0.001) and a further improvement with the addition of high HR (P < 0.001). Conclusion Compared with normal subjects, resting HR was associated with LV longitudinal myocardial function in asymptomatic T2DM patients with preserved LVEF. Our findings provide new insights on the management of T2DM patients.

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Heart rate reduction with ivabradine promotes shear stress-dependent anti-inflammatory mechanisms in arteries

Thrombosis and Haemostasis ◽

10.1160/th16-03-0214 ◽

2016 ◽

Vol 116 (07) ◽

pp. 181-190 ◽

Cited By ~ 13

Author(s):

Luong Le ◽

Hayley Duckles ◽

Torsten Schenkel ◽

Marwa Mahmoud ◽

Jordi Tremoleda ◽

...

Keyword(s):

Heart Rate ◽

Shear Stress ◽

Carotid Arteries ◽

Vascular Inflammation ◽

Protective Effects ◽

En Face ◽

Inflammatory Activation ◽

Anti Inflammatory ◽

Stress Dependent

SummaryBlood flow generates wall shear stress (WSS) which alters endothelial cell (EC) function. Low WSS promotes vascular inflammation and atherosclerosis whereas high uniform WSS is protective. Ivabradine decreases heart rate leading to altered haemodynamics. Besides its cardio-protective effects, ivabradine protects arteries from inflammation and atherosclerosis via unknown mechanisms. We hypothesised that ivabradine protects arteries by increasing WSS to reduce vascular inflammation. Hypercholesterolaemic mice were treated with ivabradine for seven weeks in drinking water or remained untreated as a control. En face immunostaining demonstrated that treatment with ivabradine reduced the expression of pro-inflammatory VCAM-1 (p<0.01) and enhanced the expression of anti-inflammatory eNOS (p<0.01) at the inner curvature of the aorta. We concluded that ivabradine alters EC physiology indirectly via modulation of flow because treatment with ivabradine had no effect in ligated carotid arteries in vivo, and did not influence the basal or TNFα-induced expression of inflammatory (VCAM-1, MCP-1) or protective (eNOS, HMOX1, KLF2, KLF4) genes in cultured EC. We therefore considered whether ivabradine can alter WSS which is a regulator of EC inflammatory activation. Computational fluid dynamics demonstrated that ivabradine treatment reduced heart rate by 20 % and enhanced WSS in the aorta. In conclusion, ivabradine treatment altered haemodynamics in the murine aorta by increasing the magnitude of shear stress. This was accompanied by induction of eNOS and suppression of VCAM-1, whereas ivabradine did not alter EC that could not respond to flow. Thus ivabradine protects arteries by altering local mechanical conditions to trigger an anti-inflammatory response.

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Signaling and cytotoxic functions of 4-hydroxyalkenals

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00508.2010 ◽

2010 ◽

Vol 299 (6) ◽

pp. E879-E886 ◽

Cited By ~ 113

Author(s):

Yael Riahi ◽

Guy Cohen ◽

Ofer Shamni ◽

Shlomo Sasson

Keyword(s):

Chemical Reactivity ◽

Cellular Functions ◽

Free Oxygen Radical ◽

Lipid Molecule ◽

Cell Functions ◽

Peroxidation Product ◽

Covalent Adducts ◽

12 Lipoxygenase ◽

Hydroperoxyeicosatetraenoic Acid ◽

In Cells

The peroxidation of n-3 and n-6 polyunsaturated fatty acids (PUFAs) and of their hydroperoxy metabolites is a complex process. It is initiated by free oxygen radical-induced abstraction of a hydrogen atom from the lipid molecule followed by a series of nonenzymatic reactions that ultimately generate the reactive aldehyde species 4-hydroxyalkenals. The molecule 4-hydroxy- 2E-hexenal (4-HHE) is generated by peroxidation of n-3 PUFAs, such as linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid. The aldehyde product 4-hydroxy-2 E-nonenal (4-HNE) is the peroxidation product of n-6 PUFAs, such as arachidonic and linoleic acids and their 15-lipoxygenase metabolites, namely 15-hydroperoxyeicosatetraenoic acid (15-HpETE) and 13-hydroperoxyoctadecadienoic acid (13-HpODE). Another reactive peroxidation product is 4-hydroxy-2 E,6 Z-dodecadienal (4-HDDE), which is derived from 12-hydroperoxyeicosatetraenoic acid (12-HpETE), the 12-lipoxygenase metabolite of arachidonic acid. Hydroxyalkenals, notably 4-HNE, have been implicated in various pathophysiological interactions due to their chemical reactivity and the formation of covalent adducts with macromolecules. The progressive accumulation of these adducts alters normal cell functions that can lead to cell death. The lipophilicity of these aldehydes positively correlates to their chemical reactivity. Nonetheless, at low and noncytotoxic concentrations, these molecules may function as signaling molecules in cells. This has been shown mostly for 4-HNE and to some extent for 4-HHE. The capacity of 4-HDDE to generate such “mixed signals” in cells has received less attention. This review addresses the origin and cellular functions of 4-hydroxyalkernals.

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