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https://www.readbyqxmd.com/read/28226463/cardiac-katp-channel-modulation-by-16hz-magnetic-fields-a-theoretical-study
#1
Yuval Aharonovich, Mickey Scheinowitz, Sharon Zlochiver, Yuval Aharonovich, Mickey Scheinowitz, Sharon Zlochiver, Yuval Aharonovich, Sharon Zlochiver, Mickey Scheinowitz
Heart exposure to 16Hz magnetic fields (MFs) was shown to be cardio-protective for diseased hearts; still, the mechanism of this effect is unknown. We hypothesize that a possible one mechanism is an increased trans-membrane KATP channel open probability due to modulation of the degree of dissociation between K(+) ions, having a resonance frequency of 16Hz, and the channel selectivity filter. The Fan-Makielski Markovian KATP channel model was adopted, and the MF bio-effect was manifested by modulating the open probability of the channel using the predictive MF bio-effect parameter based on Binhi's quantum mechanics model...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28220989/global-and-local-mechanisms-sustain-axonal-proteostasis-of-transmembrane-proteins
#2
REVIEW
Víctor Hugo Cornejo, Alejandro Luarte, Andrés Couve
The control of neuronal protein homeostasis or proteostasis is tightly regulated both spatially and temporally, assuring accurate and integrated responses to external or intrinsic stimuli. Local or autonomous responses in dendritic and axonal compartments are crucial to sustain function during development, physiology and in response to damage or disease. Axons are responsible for generating and propagating electrical impulses in neurons, and the establishment and maintenance of their molecular composition are subject to extreme constraints exerted by length and size...
February 21, 2017: Traffic
https://www.readbyqxmd.com/read/28220789/stim1-activates-crac-channels-through-rotation-of-the-pore-helix-to-open-a-hydrophobic-gate
#3
Megumi Yamashita, Priscilla S-W Yeung, Christopher E Ing, Beth A McNally, Régis Pomès, Murali Prakriya
Store-operated Ca(2+) release-activated Ca(2+) (CRAC) channels constitute a major pathway for Ca(2+) influx and mediate many essential signalling functions in animal cells, yet how they open remains elusive. Here, we investigate the gating mechanism of the human CRAC channel Orai1 by its activator, stromal interacting molecule 1 (STIM1). We find that two rings of pore-lining residues, V102 and F99, work together to form a hydrophobic gate. Mutations of these residues to polar amino acids produce channels with leaky gates that conduct ions in the resting state...
February 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28219978/a-mutation-in-the-g-protein-gene-gnb2-causes-familial-sinus-node-and-atrioventricular-conduction-dysfunction
#4
Birgit Stallmeyer, Johanna Kuß, Stefan Kotthoff, Sven Zumhagen, Kirsty S Vowinkel, Susanne Rinne, Lina A Matschke, Corinna Friedrich, Ellen Schulze-Bahr, Stephan Rust, Guiscard Seebohm, Niels Decher, Eric Schulze-Bahr
Rationale: Familial sinus node and atrioventricular (AV) conduction dysfunction is a rare disorder that leads to paroxysmal dizziness, fatigue and syncope due to a temporarily or permanent reduced heart rate. To date, only a few genes for familial sinus and/or AV conduction dysfunction are known and the majority of cases remain etiologically unresolved. Objective: We aim to identify the disease gene in a large three-generation family (n=25) with autosomal dominant sinus node dysfunction (SND) and AV block (AVB) and to characterise the mutation-related pathomechanisms in familial SND+AVB...
February 20, 2017: Circulation Research
https://www.readbyqxmd.com/read/28218274/trapping-of-ivermectin-by-a-pentameric-ligand-gated-ion-channel-upon-open-to-closed-isomerization
#5
Nurit Degani-Katzav, Moshe Klein, Moran Har-Even, Revital Gortler, Ruthi Tobi, Yoav Paas
Ivermectin (IVM) is a broad-spectrum anthelmintic drug used to treat human parasitic diseases like river blindness and lymphatic filariasis. By activating invertebrate pentameric glutamate-gated chloride channels (GluCl receptors; GluClRs), IVM induces sustained chloride influx and long-lasting membrane hyperpolarization that inhibit neural excitation in nematodes. Although IVM activates the C. elegans heteromeric GluClα/β receptor, it cannot activate a homomeric receptor composed of the C. elegans GluClβ subunits...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28217814/-effects-of-growth-differentiation-factor-15-gdf-15-on-neurological-systems-cardiovascular-diseases-and-cancer-progression
#6
Dong-Dong Liu, Yan-Ai Mei
Growth differentiation factor-15 (GDF-15) is a member of the transforming growth factor beta superfamily. GDF-15 expression is dramatically upregulated during acute brain injury, cancer, cardiovascular disease, and inflammation, suggesting its potential value as a disease biomarker. It has been suggested that GDF-15 has neurotropic effects in the nervous system. Our studies showed that GDF-15 modulated the expression of neuronal K(+) and Ca(2+) ion channels and increased the release of excitatory transmitter in the medial prefrontal cortex of mice...
February 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/28217615/type-1-brugada-pattern-electrocardiogram-induced-by-hypokalemia
#7
Thein Swe, Muhammad Hassan Dogar
Coved-type ST-segment elevation in the right precordial leads are the characteristics of Brugada syndrome, an inherited arrhythmogenic ion channel disease, which could lead to ventricular arrhythmia and sudden death. Hypokalemia alone may induce Type 1 Brugada pattern electrocardiogram (EKG), and the association has rarely been reported. We describe a patient with hypokalemia 2.9 mmol/L and the appearance of new right bundle branch block pattern with coved ST-segment elevations with inverted T wave in leads V1-V2...
July 2016: Journal of Family Medicine and Primary Care
https://www.readbyqxmd.com/read/28215304/neurotrophins-and-migraine
#8
L B Martins, A L Teixeira, R B Domingues
Neurotrophins (NTs) have been implicated in generation and modulation of nociceptive pathways. Change in NTs levels is associated with painful conditions and neurological diseases such as migraine. Currently, it is generally recognized that migraine headaches result from the activation and sensitization of trigeminal sensory afferent fibers leading to neuropeptides release such as calcitonin gene-related peptide (CGRP) and substance P (SP). This triggers an inflammatory cascade causing a neurogenic inflammation...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28213520/cholesterol-up-regulates-neuronal-g-protein-gated-inwardly-rectifying-potassium-girk-channel-activity-in-the-hippocampus
#9
Anna N Bukiya, Serdar Durdagi, Sergei Noskov, Avia Rosenhouse-Dantsker
Hypercholesterolemia is a well-known risk factor for the development of neurodegenerative disease. However, the underlying mechanisms are mostly unknown. In recent years, it has become increasingly evident that cholesterol-driven effects on physiology and pathophysiology derive from its ability to alter the function of a variety of membrane proteins including ion channels. Yet, the effect of cholesterol on G protein-gated inwardly rectifying potassium (GIRK) channels expressed in the brain is unknown. GIRK channels mediate the actions of inhibitory brain neurotransmitters...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28212798/protein-kinase-c-as-regulator-of-vascular-smooth-muscle-function-and-potential-target-in-vascular-disorders
#10
H C Ringvold, R A Khalil
Vascular smooth muscle (VSM) plays an important role in maintaining vascular tone. In addition to Ca(2+)-dependent myosin light chain (MLC) phosphorylation, protein kinase C (PKC) is a major regulator of VSM function. PKC is a family of conventional Ca(2+)-dependent α, β, and γ, novel Ca(2+)-independent δ, ɛ, θ, and η, and atypical ξ, and ι/λ isoforms. Inactive PKC is mainly cytosolic, and upon activation it undergoes phosphorylation, maturation, and translocation to the surface membrane, the nucleus, endoplasmic reticulum, and other cell organelles; a process facilitated by scaffold proteins such as RACKs...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28212021/discovery-and-development-of-1-2-bromophenyl-sulfonyl-5-methoxy-3-4-methyl-1-piperazinyl-methyl-1h-indole-dimesylate-monohydrate-suvn-502-a-novel-potent-selective-and-orally-active-serotonin-6-5-ht6-receptor-antagonist-for-potential-treatment-of-alzheimer-s
#11
Ramakrishna Nirogi, Anil Shinde, Rama Sastry Kambhampati, Abdul Rasheed Mohammed, Sangram Keshari Saraf, Rajesh Kumar Badange, Thrinath Reddy Bandyala, Venugopalarao Bhatta, Kumar Bojja, Veena Reballi, Ramkumar Subramanian, Vijay Benade, Raghava Choudary Palacharla, Gopinadh Bhyrapuneni, Pradeep Jayarajan, Vinod Goyal, Venkat Jasti
Optimization of a novel series of 3-(piperazinylmethyl) indole derivatives as 5-hydroxytryptamine-6 receptor (5-HT6R) antagonists resulted in identification of 1-[(2-bromophenyl)sulfonyl]-5-methoxy-3-[(4-methyl-1-piperazinyl)methyl]-1H-indole dimesylate monohydrate (5al, SUVN-502) as a clinical candidate for potential treatment of cognitive disorders. It has high affinity at human 5-HT6R (Ki = 2.04 nM) and selectivity over 100 target sites which include receptors, enzymes, peptides, growth factors, ion channels, steroids, immunological factors, second messengers, and prostaglandins...
February 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28211811/acidity-and-acid-sensing-ion-channels-in-the-normal-and-alzheimer-s-disease-brain
#12
Eric B Gonzales, Nathalie Sumien
Alzheimer's disease prevalence has reached epidemic proportion with very few treatment options, which are associated with a multitude of side effects. A potential avenue of research for new therapies are protons, and their associated receptor: acid-sensing ion channels (ASIC). Protons are often overlooked neurotransmitters, and proton-gated currents have been identified in the brain. Furthermore, ASICs have been determined to be crucial for proper brain function. While there is more work to be done, this review is intended to highlight protons as neurotransmitters and their role along with the role of ASICs within physiological functioning of the brain...
February 15, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28209107/gastro-intestinal-manifestations-in-cystic-fibrosis-patients
#13
REVIEW
S Van Biervliet, C de Clercq, D Declercq, E Van Braeckel, S Van Daele, F De Baets, D De Looze
Cystic fibrosis (CF) is a life-limiting disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). This defective chloride channel, present in different organ systems such as respiratory system, gastrointestinal tract, reproductive system and sweat glands, disturbs the ion and water transport over the membranes leading to the well known CF symptoms. CF has outgrown paediatric care, as half of CF patients are currently adults. The CF gastrointestinal tract has its own particularities...
September 2016: Acta Gastro-enterologica Belgica
https://www.readbyqxmd.com/read/28209036/-primary-culture-and-functional-identification-of-distal-pulmonary-artery-smooth-muscle-cells-in-mice
#14
M C Li, Y Q Chen, C T Zhang, Q Jiang, W J Lu, J Wang
Objective: To establish a method of isolation and primary culture of mice distal pulmonary artery smooth muscle cells (PASMCs) and identify the functional properties. Methods: PASMCs were harvested from the distal pulmonary artery (PA) tissue of mice by enzymatic digestion of collagenaseⅠand papain; and the growth characteristics were observed under inverted microscope and identified by Immunofluorescence technique. Effects on the intracellular calcium ion concentration of distal PASMCs were detected by Fura-2-AM fluorescent probe tracer under a fluorescence microscope in Krebs solution containing clopiazonic acid (CPA) and nifedipin (Nif)...
February 12, 2017: Chinese Journal of Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/28205574/neuropathic-pain
#15
REVIEW
Luana Colloca, Taylor Ludman, Didier Bouhassira, Ralf Baron, Anthony H Dickenson, David Yarnitsky, Roy Freeman, Andrea Truini, Nadine Attal, Nanna B Finnerup, Christopher Eccleston, Eija Kalso, David L Bennett, Robert H Dworkin, Srinivasa N Raja
Neuropathic pain is caused by a lesion or disease of the somatosensory system, including peripheral fibres (Aβ, Aδ and C fibres) and central neurons, and affects 7-10% of the general population. Multiple causes of neuropathic pain have been described and its incidence is likely to increase owing to the ageing global population, increased incidence of diabetes mellitus and improved survival from cancer after chemotherapy. Indeed, imbalances between excitatory and inhibitory somatosensory signalling, alterations in ion channels and variability in the way that pain messages are modulated in the central nervous system all have been implicated in neuropathic pain...
February 16, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28202366/modulation-of-the-trpv4-ion-channel-as-a-therapeutic-target-for-disease
#16
REVIEW
Megan S Grace, Sara J Bonvini, Maria G Belvisi, Peter McIntyre
Transient Receptor Potential Vanilloid 4 (TRPV4) is a broadly expressed, polymodally gated ion channel that plays an important role in many physiological and pathophysiological processes. TRPV4 knockout mice and several synthetic pharmacological compounds that selectively target TRPV4 are now available, which has allowed detailed investigation in to the therapeutic potential of this ion channel. Results from animal studies suggest that TRPV4 antagonism has therapeutic potential in oedema, pain, gastrointestinal disorders, and lung diseases such as cough, bronchoconstriction, pulmonary hypertension, and acute lung injury...
February 12, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28199210/trpm2-a-potential-drug-target-to-retard-oxidative-stress
#17
Jun Li, Yunling Gao, Xianying Bao, Fengna Li, Wei Yao, Zemeng Feng, Yulong Yin
The Transient Receptor Potential Melastatin 2 (TRPM2) is a member of G protein coupled receptor superfamily and a novel dual-function protein that possesses both ion channel and Adenosine 5'-DiphosPhatase Ribose (ADPR) hydrolase function. TRPM2 is involved in Ca(2+) signaling in various cells as an endogenous redox sensor for oxidative stress and reactive oxygen species, and contributes to cytokine production, insulin release, motility, Ca(2+) entry and Ca(2+)-dependent cellular reactions such as endothelial hyper-permeability and apoptosis...
March 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28199205/the-mucolipin-1-trpml1-ion-channel-transmembrane-163-tmem163-protein-and-lysosomal-zinc-handling
#18
Math P Cuajungco, Kirill Kiselyov
Lysosomes are emerging as important players in cellular zinc ion (Zn(2+)) homeostasis. The series of work on Zn2+ accumulation in the neuronal lysosomes and the mounting evidence on the role of lysosomal Zn(2+) in cell death during mammary gland involution set a biological precedent for the central role of the lysosomes in cellular Zn(2+) handling. Such a role appears to involve cytoprotection on the one hand, and cell death on the other. The recent series of work began to identify the molecular determinants of the lysosomal Zn(2+) handling...
March 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28198817/dynamic-properties-of-calcium-activated-chloride-currents-in-xenopus-laevis-oocytes
#19
Ildefonso M De la Fuente, Iker Malaina, Alberto Pérez-Samartín, María Dolores Boyano, Gorka Pérez-Yarza, Carlos Bringas, Álvaro Villarroel, María Fedetz, Rogelio Arellano, Jesus M Cortes, Luis Martínez
Chloride is the most abundant permeable anion in the cell, and numerous studies in the last two decades highlight the great importance and broad physiological role of chloride currents mediated anion transport. They participate in a multiplicity of key processes, as for instance, the regulation of electrical excitability, apoptosis, cell cycle, epithelial secretion and neuronal excitability. In addition, dysfunction of Cl(-) channels is involved in a variety of human diseases such as epilepsy, osteoporosis and different cancer types...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28193892/kv1-1-channelopathy-abolishes-presynaptic-spike-width-modulation-by-subthreshold-somatic-depolarization
#20
Umesh Vivekananda, Pavel Novak, Oscar D Bello, Yuri E Korchev, Shyam S Krishnakumar, Kirill E Volynski, Dimitri M Kullmann
Although action potentials propagate along axons in an all-or-none manner, subthreshold membrane potential fluctuations at the soma affect neurotransmitter release from synaptic boutons. An important mechanism underlying analog-digital modulation is depolarization-mediated inactivation of presynaptic Kv1-family potassium channels, leading to action potential broadening and increased calcium influx. Previous studies have relied heavily on recordings from blebs formed after axon transection, which may exaggerate the passive propagation of somatic depolarization...
February 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
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