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Ion channel disease

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https://www.readbyqxmd.com/read/28931832/mediating-role-of-trpv1-ion-channels-in-the-co-exposure-to-pm2-5-and-formaldehyde-of-balb-c-mice-asthma-model
#1
Jing Song, Jun Kang, Bencheng Lin, Jinquan Li, Yuqing Zhu, Junting Du, Xu Yang, Zhuge Xi, Rui Li
Asthma is a complex pulmonary inflammatory disease that can be promoted by air pollutants such as PM2.5 and formaldehyde (FA). However, existent experimental evidence principally focuses on the negative influence of a single air pollutant, neglecting the possible synergistic effect in biological responses to mixture of these pollutants, a more common situation in our daily life. In this study, allergic Balb/c mice were exposed to a mixture of PM2.5 and FA, and their toxicological effects and mechanisms were explored...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28928236/histone-deacetylase-inhibition-ameliorates-hypertension-and-hyperglycemia-in-a-model-of-cushing-s-syndrome
#2
Hae-Ahm Lee, Seol-Hee Kang, Mina Kim, Eunjo Lee, Hyun-Min Cho, Eun-Kyung Moon, Inkyeom Kim
Cushing's syndrome (CS) caused by hypercortisolism is occasionally accompanied by metabolic disorders such as hypertension, diabetes mellitus (DM), dyslipidemia and central obesity. Thus, morbidity and mortality, observed in cardiovascular disease, are elevated in patients with CS. We hypothesized that HDAC inhibition (HDACi) decreased transcriptional activity of glucocorticoid receptor (GR), which ameliorates hypertension and hyperglycemia in patients with CS. To establish an animal model of hypercortisolism, Sprague-Dawley rats were infused with adrenocorticotropic hormone (ACTH, 40 ng/day) or dexamethasone (Dex, 10 μg/day) via osmotic minipumps for 4 weeks...
September 19, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28927993/voltage-gated-sodium-channel-%C3%AE-subunits-the-power-outside-the-pore-in-brain-development-and-disease
#3
REVIEW
Jacob M Hull, Lori L Isom
Voltage gated sodium channels (VGSCs) were first identified in terms of their role in the upstroke of the action potential. The underlying proteins were later identified as saxitoxin and scorpion toxin receptors consisting of α and β subunits. We now know that VGSCs are heterotrimeric complexes consisting of a single pore forming α subunit joined by two β subunits; a noncovalently linked β1 or β3 and a covalently linked β2 or β4 subunit. VGSC α subunits contain all the machinery necessary for channel cell surface expression, ion conduction, voltage sensing, gating, and inactivation, in one central, polytopic, transmembrane protein...
September 16, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28925723/expression-patterns-of-members-of-the-isocitrate-dehydrogenase-gene-family-in-murine-inner-ear
#4
Y-R Kim, K-H Kim, S Lee, S-K Oh, J-W Park, K-Y Lee, J-I Baek, U-K Kim
Age-related hearing loss (ARHL) is characterized by an age-dependent decline of auditory function characterized by with loss of sensory hair cells, spiral ganglion neurons, and stria vascularis (SV) cells in the cochlea of the inner ear. Aging and age-related diseases result from accumulated oxidative damage caused by reactive oxygen species (ROS) generated by mitochondria. The isocitrate dehydrogenase (IDH) family includes three enzymes in human cells: IDH1, IDH2, and IDH3. Although all three enzymes catalyze the same enzymatic reaction, that is, oxidative decarboxylation of isocitrate to produce α-ketoglutarate, each IDH enzyme has unique features...
September 19, 2017: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
https://www.readbyqxmd.com/read/28925721/the-more-effective-treatment-of-atrial-fibrillation-applying-the-natural-compounds-as-nadph-oxidase-and-ion-channel-inhibitors
#5
Samira Barangi, A Wallace Hayes, Gholamreza Karimi
Atrial fibrillation (AF) is the most common cardiac arrhythmia that occurs because of several different risk factors, e.g., valvular heart disease, coronary artery disease, age ≥75 years, hypertension and diabetes mellitus. One key risk factor that results in AF, is oxidative stress. Evidence suggests that there is a correlation between oxidative processes and the genesis of AF. Oxidative stress occurs when the generation of reactive oxygen species (ROS) increase due to excessive activity of enzymes including NADPH oxidase (NOX) and xanthine oxidase; or its degradation decrease by dysfunctional antioxidant enzyme systems, such as superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx)...
September 19, 2017: Critical Reviews in Food Science and Nutrition
https://www.readbyqxmd.com/read/28922053/distribution-and-function-of-voltage-gated-sodium-channels-in-the-nervous-system
#6
Jun Wang, Shao-Wu Ou, Yun-Jie Wang
Voltage-gated sodium channels (VGSCs) are the basic ion channels for neuronal excitability, which are crucial for the resting potential and the generation and propagation of action potentials in neurons. To date, at least nine distinct sodium channel isoforms have been detected in the nervous system. Recent studies have identified that voltage-gated sodium channels not only play an essential role in the normal electrophysiological activities of neurons but also have a close relationship with neurological diseases...
September 18, 2017: Channels
https://www.readbyqxmd.com/read/28919940/calcitox-aging-counterbalanced-by-endogenous-farnesol-like-sesquiterpenoids-an-undervalued-evolutionarily-ancient-key-signaling-pathway
#7
Arnold De Loof
Cells are powerful miniature electrophoresis chambers, at least during part of their life cycle. They die at the moment the voltage gradient over their plasma membrane, and their ability to drive a self-generated electric current carried by inorganic ions through themselves irreversibly collapses. Senescence is likely due to the progressive, multifactorial damage to the cell's electrical system. This is the essence of the "Fading electricity theory of aging" (De Loof et al., Aging Res. Rev. 2013;12:58-66)...
2017: Communicative & Integrative Biology
https://www.readbyqxmd.com/read/28911820/regulation-of-pannexin-channels-in-the-cns-by-src-family-kinases
#8
REVIEW
Alexander W Lohman, Nicholas L Weilinger, Silva Mf Santos, Jennifer Bialecki, Allison C Werner, Connor L Anderson, Roger J Thompson
Pannexins form single membrane channels that regulate the passage of ions, small molecules and metabolites between the intra- and extracellular compartments. In the central nervous system, these channels are integrated into numerous signaling cascades that shape brain physiology and pathology. Post-translational modification of pannexins is complex, with phosphorylation emerging as a prominent form of functional regulation. While much is still not known regarding the specific kinases and modified amino acids, recent reports support a role for Src family tyrosine kinases (SFK) in regulating pannexin channel activity...
September 11, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28911739/role-of-inward-rectifier-potassium-channels-in-salivary-gland-function-and-sugar-feeding-of-the-fruit-fly-drosophila-melanogaster
#9
Daniel R Swale, Zhilin Li, Felix Guerrero, Adalberto A Pérez De León, Lane D Foil
The arthropod salivary gland is of critical importance for horizontal transmission of pathogens, yet a detailed understanding of the ion conductance pathways responsible for saliva production and excretion is lacking. A superfamily of potassium ion channels, known as inward rectifying potassium (Kir) channels, is overexpressed in the Drosophila salivary gland by 32-fold when compared to the whole body mRNA transcripts. Therefore, we aimed to test the hypothesis that pharmacological and genetic depletion of salivary gland specific Kir channels alters the efficiency of the gland and reduced feeding capabilities using the fruit fly Drosophila melanogaster as a model organism that could predict similar effects in arthropod disease vectors...
September 2017: Pesticide Biochemistry and Physiology
https://www.readbyqxmd.com/read/28906438/acetylcholinesterase-and-nicotinic-acetylcholine-receptors-in-schistosomes-and-other-parasitic-helminths
#10
REVIEW
Hong You, Chang Liu, Xiaofeng Du, Donald P McManus
Schistosomiasis, which is caused by helminth trematode blood flukes of the genus Schistosoma, is a serious health and economic problem in tropical areas, and the second most prevalent parasitic disease after malaria. Currently, there is no effective vaccine available and treatment is entirely dependent on a single drug, praziquantel (PZQ), raising a significant potential public health threat due to the emergence of PZQ drug resistance. It is thus urgent and necessary to explore novel therapeutic targets for the treatment of schistosomiasis...
September 14, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28904867/the-asparagine-533-residue-in-the-outer-pore-loop-region-of-the-mouse-pkd2l1-channel-is-essential-for-its-voltage-dependent-inactivation
#11
Takahiro Shimizu, Taiga Higuchi, Toshihiro Toba, Chie Ohno, Takuto Fujii, Bernd Nilius, Hideki Sakai
Voltage-dependent inactivation of ion channels contributes to the regulation of the membrane potential of excitable cells. Mouse polycystic kidney disease 2-like 1 (PKD2L1) forms voltage-dependent nonselective cation channels, which are activated but subsequently inactivated in response to membrane depolarization. Here, we found that the mutation of an asparagine 533 residue (N533Q) in the outer pore loop region of PKD2L1 caused a marked increase in outward currents induced by depolarization. In addition, the tail current analysis demonstrated that the N533Q mutants are activated during depolarization but the subsequent inactivation does not occur...
September 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28903775/nonclinical-and-clinical-pharmacology-evidence-for-cardiovascular-safety-of-saxagliptin
#12
REVIEW
Pia S Pollack, Kristina D Chadwick, David M Smith, Martin Billger, Boaz Hirshberg, Nayyar Iqbal, David W Boulton
BACKGROUND: In the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR) trial in patients with type 2 diabetes mellitus (T2D) at high risk of cardiovascular (CV) disease, saxagliptin did not increase the risk for major CV adverse events. However, there was an unexpected imbalance in events of hospitalization for heart failure (hHF), one of six components of the secondary CV composite endpoint, with a greater number of events observed with saxagliptin...
September 13, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28901280/neuronal-and-extraneuronal-nicotinic-acetylcholine-receptors
#13
Michele Zoli, Susanna Pucci, Antonietta Vilella, Cecilia Gotti
Neuronal nicotinic acetylcholine receptors (nAChRs) belong to a super-family of Cys-loop ligand-gated ion channels that respond to endogenous acetylcholine (ACh) or other cholinergic ligands. These receptors are also the targets of drugs such as nicotine (the main addictive agent delivered by cigarette smoke) and are involved in a variety of physiological and pathophysiological processes. Numerous studies have shown that the expression and/or function of nAChRs is compromised in many neurological and psychiatric diseases...
September 11, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28900930/cardiac-remodeling-and-disease-soce-and-trpc-signaling-in-cardiac-pathology
#14
Petra Eder
TRPC channels have been suggested as potential candidates mediating store-operated Ca(2+) entry (SOCE) in cardiomyocytes. There is increasing evidence that the TRPC isoforms TRPC1 and TRPC4 might fulfill the function as SOCs, in concert with or in parallel to the key players of SOCE, Orai1, and STIM1. Several other isoforms, e.g., TRPC3, TRPC6, and TRPC7, might rather associate to receptor-activated diacylglycerol (DAG)-sensitive ion channels. However, the exact activation mode has not been elucidated yet, given the characteristic of TRPC channels to heteromerize to unpredictable ion channel assemblies...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28898996/the-expression-of-the-rare-caveolin-3-variant-t78m-alters-cardiac-ion-channels-function-and-membrane-excitability
#15
Giulia Campostrini, Mattia Bonzanni, Alessio Lissoni, Claudia Bazzini, Raffaella Milanesi, Elena Vezzoli, Maura Francolini, Mirko Baruscotti, Annalisa Bucchi, Ilaria Rivolta, Matteo Fantini, Stefano Severi, Riccardo Cappato, Lia Crotti, Peter J Schwartz, Dario DiFrancesco, Andrea Barbuti
Aims: Caveolinopathies are a family of genetic disorders arising from alterations of the caveolin-3 (cav-3) gene. The T78M cav-3 variant has been associated with both skeletal and cardiac muscle pathologies but its functional contribution, especially to cardiac diseases, is still controversial. Here, we evaluated the effect of the T78M cav-3 variant on cardiac ion channel function and membrane excitability. Methods and results: We transfected either the wild type (WT) or T78M cav-3 in caveolin-1 knock-out mouse embryonic fibroblasts and found by immunofluorescence and electron microscopy that both are expressed at the plasma membrane and form caveolae...
August 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28892643/comparison-of-the-effects-of-i-sub-k-ach-sub-i-sub-kr-sub-and-i-sub-na-sub-block-in-conscious-dogs-with-atrial-fibrillation-and-on-action-potentials-in-remodeled-atrial-trabeculae
#16
Viktor Juhász, Tibor Hornyik, Attila Benák, Norbert Nagy, Zoltan Husti, Robert Pap, László Sághy, László Virág, András Varró, István Baczkó
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and a major cause of morbidity and mortality. Traditional antiarrhythmic agents used for restoration of sinus rhythm have limited efficacy in long-term AF and they may possess ventricular proarrhythmic adverse effects, especially in patients with structural heart disease. The acetylcholin receptor-activated potassium channel (I<sub>K,ACh</sub>) represents an atrial-selective target for future AF management. We investigated the effects of the I<sub>K,ACh</sub> blocker tertiapin-Q (TQ), a derivative of the honeybee toxin tertiapin, on chronic atrial tachypacing induced AF in conscious dogs, without the influence of anesthetics that modulate a number of cardiac ion channels...
September 11, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28884460/potassium-channels-a-potential-therapeutic-target-for-parkinson-s-disease
#17
REVIEW
Xiaoyan Chen, Bao Xue, Jun Wang, Haixia Liu, Limin Shi, Junxia Xie
The pathogenesis of the second major neurodegenerative disorder, Parkinson's disease (PD), is closely associated with the dysfunction of potassium (K(+)) channels. Therefore, PD is also considered to be an ion channel disease or neuronal channelopathy. Mounting evidence has shown that K(+) channels play crucial roles in the regulations of neurotransmitter release, neuronal excitability, and cell volume. Inhibition of K(+) channels enhances the spontaneous firing frequency of nigral dopamine (DA) neurons, induces a transition from tonic firing to burst discharge, and promotes the release of DA in the striatum...
September 7, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28883612/human-electronegative-low-density-lipoprotein-modulates-cardiac-repolarization-via-lox-1-mediated-alteration-of-sarcolemmal-ion-channels
#18
An-Sheng Lee, Yutao Xi, Chin-Hu Lai, Wei-Yu Chen, Hsien-Yu Peng, Hua-Chen Chan, Chu-Huang Chen, Kuan-Cheng Chang
Dyslipidemia is associated with greater risk of ventricular tachyarrhythmias in patients with cardiovascular diseases. We aimed to examine whether the most electronegative subfraction of low-density lipoprotein (LDL), L5, is correlated with QTc prolongation in patients with coronary artery disease (CAD) and investigate the effects of human L5 on the electrophysiological properties of cardiomyocytes in relation to the lectin-like oxidized LDL receptor (LOX-1). L5 was isolated from the plasma of 40 patients with angiography documented CAD and 13 patients with no CAD to correlate the QTc interval respectively...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28878326/swapping-of-transmembrane-domains-in-the-epithelial-calcium-channel-trpv6
#19
Appu K Singh, Kei Saotome, Alexander I Sobolevsky
Tetrameric ion channels have either swapped or non-swapped arrangements of the S1-S4 and pore domains. Here we show that mutations in the transmembrane domain of TRPV6 can result in conversion from a domain-swapped to non-swapped fold. These results reveal structural determinants of domain swapping and raise the possibility that a single ion channel subtype can fold into either arrangement in vivo, affecting its function in normal or disease states.
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28877958/proline-dependent-and-basophilic-kinases-phosphorylate-human-trpc6-at-serine-14-to-control-channel-activity-through-increased-membrane-expression
#20
Henning Hagmann, Nicole Mangold, Markus M Rinschen, Tim Koenig, Karl Kunzelmann, Bernhard Schermer, Thomas Benzing, Paul T Brinkkoetter
Signaling via the transient receptor potential (TRP) ion channel C6 plays a pivotal role in hereditary and sporadic glomerular kidney disease. Several studies have identified gain-of-function mutations of TRPC6 and report induced expression and enhanced channel activity of TRPC6 in association with glomerular diseases. Interfering with TRPC6 activity may open novel therapeutic pathways. TRPC6 channel activity is controlled by protein expression and stability as well as intracellular trafficking. Identification of regulatory phosphorylation sites in TRPC6 and corresponding protein kinases is essential to understand the regulation of TRPC6 activity and may result in future therapeutic strategies...
September 6, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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