scholarly journals A Cardioplegic Solution with an Understanding of a Cardiochannelopathy

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1878
Author(s):  
Min Jeong Ji ◽  
Jeong Hee Hong
Keyword(s):  
Ion Channels ◽  
Cardiac Function ◽  
Water Channel ◽  
Electrolyte Transport ◽  
Cardioplegic Solution ◽  
Cardiac Pathology ◽  
Insight Into

Cardiac surgeries have been improved by accompanying developing cardioplegia solutions. However, the cardioplegia application presents an ongoing challenge with a view of a sufficiently restored cardiac function. In this review, we focus on the cardioplegia-induced mechanism and summarize the findings of studies undertaken to improve cardioprotective strategies. Currently, and somewhat surprisingly, relatively little is known about cardiac electrolyte regulation through channel physiology. We hope that an improved understanding of the electrolyte transport through ion channels/transporters and modulations of water channel aquaporins will provide an insight into cardiac channel physiology and a channel-based cardiac pathology of a cardiochannelopathy.

scholarly journals Systemic and heart autonomous effects of sphingosine Δ4 desaturase deficiency in lipotoxic cardiac pathophysiology

2020 ◽  
Vol 13 (8) ◽  
pp. dmm043083
Author(s):  
Stanley M. Walls ◽  
Dale A. Chatfield ◽  
Karen Ocorr ◽  
Greg L. Harris ◽  
Rolf Bodmer
Keyword(s):  
Cardiac Function ◽  
Fat Body ◽  
Model Systems ◽  
Specific Expression ◽  
Cardiac Pathology ◽  
Cardiac Chamber ◽  
Spatial Regulation ◽  
Cardiac Pathophysiology ◽  
Cardiac Steatosis ◽  
Fractional Shortening

ABSTRACTLipotoxic cardiomyopathy (LCM) is characterized by cardiac steatosis, including the accumulation of fatty acids, triglycerides and ceramides. Model systems have shown the inhibition of ceramide biosynthesis to antagonize obesity and improve insulin sensitivity. Sphingosine Δ4 desaturase (encoded by ifc in Drosophila melanogaster) enzymatically converts dihydroceramide into ceramide. Here, we examine ifc mutants to study the effects of desaturase deficiency on cardiac function in Drosophila. Interestingly, ifc mutants exhibited classic hallmarks of LCM: cardiac chamber dilation, contractile defects and loss of fractional shortening. This outcome was phenocopied in global ifc RNAi-mediated knockdown flies. Surprisingly, cardiac-specific ifc knockdown flies exhibited cardiac chamber restriction with no contractile defects, suggesting heart autonomous and systemic roles for ifc activity in cardiac function. Next, we demonstrated that ifc mutants exhibit suppressed Sphingosine kinase 1 (Sk1) expression. Ectopic overexpression of Sk1 was sufficient to prevent cardiac chamber dilation and loss of fractional shortening in ifc mutants. Partial rescue was also observed with cardiac- and fat-body-specific Sk1 overexpression. Finally, we showed that cardiac-specific expression of Drosophila inhibitor of apoptosis (dIAP) also prevented cardiac dysfunction in ifc mutants, suggesting a role for caspase activity in the observed cardiac pathology. Collectively, we show that spatial regulation of sphingosine Δ4 desaturase activity differentially affects cardiac function in heart autonomous and systemic mechanisms through tissue interplay.

Regulation of the water channel aquaporin-2 by posttranslational modification

2011 ◽  
Vol 300 (5) ◽  
pp. F1062-F1073 ◽  
Author(s):  
Hanne B. Moeller ◽  
Emma T. B. Olesen ◽  
Robert A. Fenton
Keyword(s):  
Membrane Proteins ◽  
Protein Interactions ◽  
Posttranslational Modifications ◽  
Posttranslational Modification ◽  
Water Channel ◽  
Cellular Functions ◽  
Aquaporin 2 ◽  
Eukaryotic Membrane Proteins ◽  
Insight Into

The cellular functions of many eukaryotic membrane proteins, including the vasopressin-regulated water channel aquaporin-2 (AQP2), are regulated by posttranslational modifications. In this article, we discuss the experimental discoveries that have advanced our understanding of how posttranslational modifications affect AQP2 function, especially as they relate to the role of AQP2 in the kidney. We review the most recent data demonstrating that glycosylation and, in particular, phosphorylation and ubiquitination are mechanisms that regulate AQP2 activity, subcellular sorting and distribution, degradation, and protein interactions. From a clinical perspective, posttranslational modification resulting in protein misrouting or degradation may explain certain forms of nephrogenic diabetes insipidus. In addition to providing major insight into the function and dynamics of renal AQP2 regulation, the analysis of AQP2 posttranslational modification may provide general clues as to the role of posttranslational modification for regulation of other membrane proteins.

scholarly journals β-Adrenergic receptor desensitization in man: insight into post-exercise attenuation of cardiac function

2006 ◽  
Vol 577 (2) ◽  
pp. 717-725 ◽  
Author(s):  
Emma Hart ◽  
Ellen Dawson ◽  
Peter Rasmussen ◽  
Keith George ◽  
Niels H. Secher ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Adrenergic Receptor ◽  
Receptor Desensitization ◽  
Post Exercise ◽  
Insight Into

Influence of Rub-Grooves on Labyrinth Seal Leakage

2003 ◽  
Vol 125 (2) ◽  
pp. 387-393 ◽  
Author(s):  
J. Denecke ◽  
V. Schramm ◽  
S. Kim ◽  
S. Wittig
Keyword(s):  
Gas Turbines ◽  
Water Channel ◽  
Large Data ◽  
Labyrinth Seal ◽  
Labyrinth Seals ◽  
Data Set ◽  
Engine Efficiency ◽  
Discharge Coefficients ◽  
Flow Mechanisms ◽  
Insight Into

An experimental investigation on the influence of stator rub-grooves on labyrinth seal leakage is presented in the present paper. In current labyrinth seal designs, abradable lands allow the rotor labyrinth teeth to rub grooves into the stator. These rub-grooves have a large influence on the seal leakage characteristic and impair the overall engine efficiency. To improve the understanding of rub-groove effects, discharge coefficients were determined using a plain nonrotating labyrinth seal model of scale 4:1 considering a wide variation of rub-groove geometries at different seal clearances. Three labyrinth seal types were covered in this investigation that are generally used in gas turbines, namely 1) straight-through labyrinth seals, 2) stepped labyrinth seals with forward facing steps, and 3) stepped labyrinth seals with backward facing steps. To attain a deeper insight into the flow mechanisms, water-channel visualizations were performed. The large data set generated in this study, provides the basis to analyze and quantify the influence of rub-grooves on the seal leakage for the three aforementioned labyrinth seal types. Current results were in agreement with previous studies on worn labyrinth seals for several seal geometries.

Tinnitus: Prospects for Pharmacological Interventions With a Seesaw Model

2017 ◽  
Vol 24 (4) ◽  
pp. 353-367 ◽  
Author(s):  
Hannah Tetteh ◽  
Minseok Lee ◽  
C. Geoffrey Lau ◽  
Sunggu Yang ◽  
Sungchil Yang
Keyword(s):  
Ion Channels ◽  
Modern Society ◽  
Anxiety And Depression ◽  
Pharmacological Interventions ◽  
Ongoing Research ◽  
Neuronal Excitation ◽  
Seesaw Model ◽  
Future Direction ◽  
Insight Into

Chronic tinnitus, the perception of lifelong constant ringing in ear, is one capital cause of disability in modern society. It is often present with various comorbid factors that severely affect quality of life, including insomnia, deficits in attention, anxiety, and depression. Currently, there are limited therapeutic treatments for alleviation of tinnitus. Tinnitus can involve a shift in neuronal excitation/inhibition (E/I) balance, which is largely modulated by ion channels and receptors. Thus, ongoing research is geared toward pharmaceutical approaches that modulate the function of ion channels and receptors. Here, we propose a seesaw model that delineates how tinnitus-related ion channels and receptors are involved in homeostatic E/I balance of neurons. This review provides a thorough account of our current mechanistic understanding of tinnitus and insight into future direction of drug development.

scholarly journals An Overview of Cardiac Management in Neuromuscular Disease

2016 ◽  
Vol 10 (1) ◽  
pp. 82-88
Author(s):  
Renee M. Hickey ◽  
John D. Cullen ◽  
George M. Sachs
Keyword(s):  
Muscular Dystrophy ◽  
Cardiac Function ◽  
Myasthenia Gravis ◽  
Neuromuscular Disease ◽  
Neuromuscular Disorders ◽  
Cardiovascular Complications ◽  
Muscular Dystrophies ◽  
Cardiac Pathology ◽  
Life Threatening

Muscular dystrophy and myasthenia gravis are two neuromuscular disorders that can involve significant cardiovascular complications. The frequency and severity of cardiac pathology varies widely among the muscular dystrophies. In some, it is nearly inevitable and requires regular evaluation. In others, assessment of cardiac function can be more symptom-driven. On-ly a minority of myasthenic patients manifest disease-related cardiovascular complications; however, their presentation can be rapidly progressive and life-threatening..

scholarly journals High-throughput characterization of 309 photocrosslinker-bearing ASIC1a variants maps residues critical for channel function and pharmacology

2020 ◽  
Author(s):  
Nina Braun ◽  
Søren Friis ◽  
Christian Ihling ◽  
Andrea Sinz ◽  
Jacob Andersen ◽  
...  
Keyword(s):  
Ion Channels ◽  
High Throughput ◽  
Mammalian Cells ◽  
Great Precision ◽  
Pharmacological Modulation ◽  
Current Decay ◽  
Human Acid ◽  
Automated Patch Clamp ◽  
Insight Into

AbstractIncorporation of non-canonical amino acids (ncAAs) can endow proteins with novel functionalities, such as crosslinking or fluorescence. In ion channels, the function of these variants can be studied with great precision using standard electrophysiology, but this approach is typically labor intensive and low throughput. Here, we establish a high-throughput protocol to conduct functional and pharmacological investigations of ncAA-containing hASIC1a (human acid-sensing ion channel 1a) variants in transiently transfected mammalian cells. We introduce three different photocrosslinking ncAAs into 103 positions and assess the function of the resulting 309 variants with automated patch-clamp (APC). We demonstrate that the approach is efficient and versatile, as it is amenable to assessing even complex pharmacological modulation by peptides. The data show that the acidic pocket is a major determinant for current decay and live-cell crosslinking provides insight into the hASIC1a-psalmotoxin-1 interaction. Overall, this protocol will enable future APC-based studies of ncAA-containing ion channels in mammalian cells.

scholarly journals OSCA/TMEM63 are an evolutionarily conserved family of mechanically activated ion channels

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Swetha E Murthy ◽  
Adrienne E Dubin ◽  
Tess Whitwam ◽  
Sebastian Jojoa-Cruz ◽  
Stuart M Cahalan ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Ion Channels ◽  
Ion Channel ◽  
Molecular Mechanisms ◽  
Deep Insight ◽  
Evolutionarily Conserved ◽  
Bona Fide ◽  
Physical Forces ◽  
Insight Into

Mechanically activated (MA) ion channels convert physical forces into electrical signals, and are essential for eukaryotic physiology. Despite their importance, few bona-fide MA channels have been described in plants and animals. Here, we show that various members of the OSCA and TMEM63 family of proteins from plants, flies, and mammals confer mechanosensitivity to naïve cells. We conclusively demonstrate that OSCA1.2, one of the Arabidopsis thaliana OSCA proteins, is an inherently mechanosensitive, pore-forming ion channel. Our results suggest that OSCA/TMEM63 proteins are the largest family of MA ion channels identified, and are conserved across eukaryotes. Our findings will enable studies to gain deep insight into molecular mechanisms of MA channel gating, and will facilitate a better understanding of mechanosensory processes in vivo across plants and animals.

Neuropeptide Y and its receptors in ventricular endocardial endothelial cells

2017 ◽  
Vol 95 (10) ◽  
pp. 1224-1229 ◽  
Author(s):  
Danielle Jacques ◽  
Pedro D’Orléans-Juste ◽  
Sheldon Magder ◽  
Ghassan Bkaily
Keyword(s):  
Heart Failure ◽  
Endothelial Cells ◽  
Cardiac Function ◽  
Neuropeptide Y ◽  
Entry And Exit ◽  
Cardiac Pathology ◽  
Contraction Coupling ◽  
Endocardial Endothelial Cells ◽  
The Right ◽  
Cardiac Excitation

Endocardial endothelial cells (EECs) constitute an important component of the heart. These cells form a monolayer that covers the cavities of the right (EECRs) and left (EECLs) ventricles. They play an important role in cardiac excitation–contraction coupling via their secretion of cardioactive factors such as neuropeptide Y (NPY). They also contribute to cardiac pathology such as arrhythmia, hypertrophy, and heart failure. Differences between EECRs and EECLs contribute to tuning of circulating factors at the entry and exit of the ventricles. NPY, via activation of its receptors, modulates the excitation–secretion coupling of EECs, thus, indirectly modulating cardiac function and remodeling.

scholarly journals Quantifying the cooperative subunit action in a multimeric membrane receptor

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Nisa Wongsamitkul ◽  
Vasilica Nache ◽  
Thomas Eick ◽  
Sabine Hummert ◽  
Eckhard Schulz ◽  
...  
Keyword(s):  
Ion Channels ◽  
Ligand Binding ◽  
Cyclic Nucleotide ◽  
Binding Sites ◽  
Membrane Receptor ◽  
Membrane Receptors ◽  
Cooperative Action ◽  
The Individual ◽  
Insight Into

Abstract In multimeric membrane receptors the cooperative action of the subunits prevents exact knowledge about the operation and the interaction of the individual subunits. We propose a method that permits quantification of ligand binding to and activation effects of the individual binding sites in a multimeric membrane receptor. The power of this method is demonstrated by gaining detailed insight into the subunit action in olfactory cyclic nucleotide-gated CNGA2 ion channels.

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