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https://www.readbyqxmd.com/read/29352184/expression-and-relevance-of-the-g-protein-gated-k-channel-in-the-mouse-ventricle
#1
Allison Anderson, Kanchan Kulkarni, Ezequiel Marron Fernandez de Velasco, Nicholas Carlblom, Zhilian Xia, Atsushi Nakano, Kirill A Martemyanov, Elena G Tolkacheva, Kevin Wickman
The atrial G protein-gated inwardly rectifying K+ (GIRK) channel is a critical mediator of parasympathetic influence on cardiac physiology. Here, we probed the details and relevance of the GIRK channel in mouse ventricle. mRNAs for the atrial GIRK channel subunits (GIRK1, GIRK4), M2 muscarinic receptor (M2R), and RGS6, a negative regulator of atrial GIRK-dependent signaling, were detected in mouse ventricle at relatively low levels. The cholinergic agonist carbachol (CCh) activated small GIRK currents in adult wild-type ventricular myocytes that exhibited relatively slow kinetics and low CCh sensitivity; these currents were absent in ventricular myocytes from Girk1-/- or Girk4-/- mice...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352128/phosphorylation-of-the-transient-receptor-potential-ankyrin-1-by-cyclin-dependent-kinase-5-affects-chemo-nociception
#2
Bradford E Hall, Michaela Prochazkova, Matthew R Sapio, Paul Minetos, Natalya Kurochkina, B K Binukumar, Niranjana D Amin, Anita Terse, John Joseph, Stephen J Raithel, Andrew J Mannes, Harish C Pant, Man-Kyo Chung, Michael J Iadarola, Ashok B Kulkarni
Cyclin-dependent kinase 5 (Cdk5) is a key neuronal kinase that is upregulated during inflammation, and can subsequently modulate sensitivity to nociceptive stimuli. We conducted an in silico screen for Cdk5 phosphorylation sites within proteins whose expression was enriched in nociceptors and identified the chemo-responsive ion channel Transient Receptor Potential Ankyrin 1 (TRPA1) as a possible Cdk5 substrate. Immunoprecipitated full length TRPA1 was shown to be phosphorylated by Cdk5 and this interaction was blocked by TFP5, an inhibitor that prevents activation of Cdk5...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352074/aldosterone-sgk1-and-ion-channels-in-the-kidney
#3
REVIEW
William C Valinsky, Rhian M Touyz, Alvin Shrier
Hyperaldosteronism, a common cause of hypertension, is strongly connected to Na+, K+, and Mg2+ dysregulation. Owing to its steroidal structure, aldosterone is an active transcriptional modifier when bound to the mineralocorticoid receptor (MR) in cells expressing the enzyme 11β-hydroxysteroid dehydrogenase 2, such as those comprising the aldosterone-sensitive distal nephron (ASDN). One such up-regulated protein, the ubiquitous serum and glucocorticoid regulated kinase 1 (SGK1), has the capacity to modulate the surface expression and function of many classes of renal ion channels, including those that transport Na+ (ENaC), K+ (ROMK/BK), Ca2+ (TRPV4/5/6), Mg2+ (TRPM7/6), and Cl- (ClC-K, CFTR)...
January 31, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29351511/chemogenetic-tools-for-causal-cellular-and-neuronal-biology
#4
Deniz Atasoy, Scott M Sternson
Chemogenetic technologies enable selective pharmacological control of specific cell populations. An increasing number of approaches have been developed that modulate different signaling pathways. Selective pharmacological control over G protein-coupled receptor signaling, ion channel conductances, protein association, protein stability, and small molecule targeting allows modulation of cellular processes in distinct cell types. Here, we review these chemogenetic technologies and instances of their applications in complex tissues in vivo and ex vivo...
January 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29351460/macrophage-dependent-impairment-of-%C3%AE-2-adrenergic-autoreceptor-function-in-sympathetic-neurons-from-doca-salt-but-not-high-fat-diet-induced-hypertensive-rats
#5
Ryan Kwun-Yee Mui, Roxanne Fernandes, Hannah Garver, Nico van Rooijen, James J Galligan
DOCA-salt and obesity-related hypertension are associated with inflammation and sympathetic nervous system hyperactivity. Prejunctional α2-adrenergic receptors (α2ARs) provide negative feedback to norepinephrine release from sympathetic nerves through inhibition of N-type Ca2+ channels. Increased neuronal norepinephrine release in DOCA-salt and obesity-related hypertension occurs through impaired α2AR signaling, however, the mechanisms involved are unclear. Mesenteric arteries are resistance arteries that receive sympathetic innervation from the superior mesenteric and celiac ganglia (SMCG)...
January 5, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29351449/personalized-medicine-in-cf-from-modulator-development-to-therapy-for-cystic-fibrosis-patients-with-rare-cftr-mutations
#6
Misak Harutyunyan, Yunjie Huang, Kyu-Shik Mun, Fanmuyi Yang, Kavisha Arora, Anjaparavanda P Naren
Cystic fibrosis (CF) is the most common life-shortening genetic disease affecting approximately 1 in 3500 of the Caucasian population. CF is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. To date, over 2000 CFTR mutations have been identified and produce a wide range of phenotypes. The CFTR protein, a chloride channel, is normally expressed on epithelial cells lining the lung, gut, and exocrine glands. Mutations in CFTR have led to pleiotropic effects in CF patients and have resulted in early morbidity and mortality...
December 14, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29351410/hypoxia-selectively-upregulates-cation-channels-and-increases-cytosolic-ca2-in-pulmonary-but-not-coronary-arterial-smooth-muscle-cells
#7
Xi He, Shanshan Song, Ramon J Ayon, Angela Balisterieri, Stephen M Black, Ayako Makino, W Gil Wier, Wei-Jin Zang, Jason X-J Yuan
Ca2+ signaling, particularly the mechanism via store-operated Ca2+ entry (SOCE) and receptor-operated Ca2+ entry (ROCE), plays a critical role in the development of acute hypoxia-induced pulmonary vasoconstriction and chronic hypoxia-induced pulmonary hypertension. This study aimed to test the hypothesis that chronic hypoxia differentially regulates the expression of proteins that mediate SOCE and ROCE (STIM, Orai, and TRPC6) in pulmonary (PASMC) and coronary (CASMC) artery smooth muscle cells. The resting cytosolic [Ca2+] ([Ca2+]cyt) and the stored [Ca2+] in the sarcoplasmic reticulum (SR) were not different in CASMC and PASMC...
January 3, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29351409/pharmacological-activation-of-ppar%C3%AE-inhibits-hypoxia-induced-proliferation-through-a-caveolin-1-targeted-and-dependent-mechanism-in-pasmcs
#8
Kai Yang, Mingming Zhao, Junyi Huang, Chenting Zhang, Qiu Yu Zheng, Yuqin Chen, Haiyang Jiang, Wenju Lu, Jian Wang
Previously, we and others have demonstrated that activation of peroxisome proliferator- activated receptor γ (PPARγ) by specific pharmacological agonists inhibits the pathogenesis of chronic hypoxia-induced pulmonary hypertension (CHPH) by suppressing the proliferation and migration in distal pulmonary arterial smooth muscle cells (PASMCs). Moreover, these beneficial effects of PPARγ are mediated by targeting the intracellular calcium homeostasis and store-operated calcium channel (SOCC) proteins, including the main caveolae component caveolin-1...
January 3, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29351391/the-bile-acids-deoxycholic-acid-and-ursodeoxycholic-acid-regulate-colonic-epithelial-wound-healing
#9
Magdalena S Mroz, Natalia K Lajczak, Bridie J Goggins, Simon Keely, Stephen Joseph Keely
The intestinal epithelium constitutes an innate barrier which, upon injury, undergoes self-repair processes known as restitution. Although, bile acids are known as important regulators of epithelial function in health and disease, their effects on wound healing processes are not yet clear. Here we set out to investigate the effects of the colonic bile acids, deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) on epithelial restitution. Wound healing in T84 cell monolayers grown on transparent, permeable, supports was assessed over 48 hrs {plus minus} bile acids...
January 11, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29351212/changes-in-the-expression-of-aqp4-and-aqp9-in-the-hippocampus-following-eclampsia-like-seizure
#10
Xinjia Han, Qian Huang, Lei Liu, Xiaoyan Sha, Bihui Hu, Huishu Liu
Eclampsia is a hypertensive disorder of pregnancy that is defined by the new onset of grand mal seizures on the basis of pre-eclampsia. Until now, the mechanisms underlying eclampsia were poorly understood. Brain edema is considered a leading cause of eclamptic seizures; aquaporins (AQP4 and AQP9), the glial water channel proteins mainly expressed in the nervous system, play an important role in brain edema. We studied AQP4 and AQP9 expression in the hippocampus of pre-eclamptic and eclamptic rats in order to explore the molecular mechanisms involved in brain edema...
January 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29350911/a-programmable-dna-origami-platform-for-organizing-intrinsically-disordered-nucleoporins-within-nanopore-confinement
#11
Patrick D Ellis Fisher, Qi Shen, Bernice Akpinar, Luke K Davis, Kenny Kwok Hin Chung, David Baddeley, Andela Saric, Thomas J Melia, Bart W Hoogenboom, Chenxiang Lin, C Patrick Lusk
Nuclear pore complexes (NPCs) form gateways that control molecular exchange between the nucleus and the cytoplasm. They impose a diffusion barrier to macromolecules and enable the selective transport of nuclear transport receptors with bound cargo. The underlying mechanisms that establish these permeability properties remain to be fully elucidated, but require unstructured nuclear pore proteins rich in Phe-Gly (FG)-repeat domains of different types, such as FxFG and GLFG. While physical modeling and in vitro approaches have provided a framework for explaining how the FG network contributes to the barrier and transport properties of the NPC, it remains unknown whether the number and/or the spatial positioning of different FG-domains along a cylindrical, ~40 nm diameter transport channel contributes to their collective properties and function...
January 19, 2018: ACS Nano
https://www.readbyqxmd.com/read/29348619/cytokine-mediated-changes-in-k-channel-activity-promotes-an-adaptive-ca2-response-that-sustains-%C3%AE-cell-insulin-secretion-during-inflammation
#12
Matthew T Dickerson, Avery M Bogart, Molly K Altman, Sarah C Milian, Kelli L Jordan, Prasanna K Dadi, David A Jacobson
Cytokines present during low-grade inflammation contribute to β-cell dysfunction and diabetes. Cytokine signaling disrupts β-cell glucose-stimulated Ca2+ influx (GSCI) and endoplasmic reticulum (ER) Ca2+ ([Ca2+]ER) handling, leading to diminished glucose-stimulated insulin secretion (GSIS). However, cytokine-mediated changes in ion channel activity that alter β-cell Ca2+ handling remain unknown. Here we investigated the role of K+ currents in cytokine-mediated β-cell dysfunction. Kslow currents, which control the termination of intracellular Ca2+ ([Ca2+]i) oscillations, were reduced following cytokine exposure...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348563/disruption-of-cxcr3-function-impedes-the-development-of-sj%C3%A3-gren-s-syndrome-like-xerostomia-in-non-obese-diabetic-mice
#13
Jing Zhou, Qing Yu
The chemokine receptor CXCR3 plays an important role in T cell recruitment in various immune responses and autoimmune diseases. Expression of CXCR3 ligands, including CXCL9, CXCL10, and CXCL11, is elevated in the salivary glands of patients with Sjögren's syndrome (SS). To elucidate whether interaction between CXCR3 and its ligands is required for the development of SS, we administrated an anti-CXCR3 blocking antibody (CXCR3-173) to the non-obese diabetic (NOD) mice, a well-defined model of SS, during the stage prior to disease onset...
January 18, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29348211/membrane-protein-insertion-through-a-mitochondrial-%C3%AE-barrel-gate
#14
Alexandra I C Höhr, Caroline Lindau, Christophe Wirth, Jian Qiu, David A Stroud, Stephan Kutik, Bernard Guiard, Carola Hunte, Thomas Becker, Nikolaus Pfanner, Nils Wiedemann
The biogenesis of mitochondria, chloroplasts, and Gram-negative bacteria requires the insertion of β-barrel proteins into the outer membranes. Homologous Omp85 proteins are essential for membrane insertion of β-barrel precursors. It is unknown if precursors are threaded through the Omp85-channel interior and exit laterally or if they are translocated into the membrane at the Omp85-lipid interface. We have mapped the interaction of a precursor in transit with the mitochondrial Omp85-channel Sam50 in the native membrane environment...
January 19, 2018: Science
https://www.readbyqxmd.com/read/29348055/high-resolution-structures-of-mitochondrial-ribosomes-and-their-functional-implications
#15
REVIEW
Philipp Bieri, Basil J Greber, Nenad Ban
Mitochondrial ribosomes (mitoribosomes) almost exclusively synthesize essential components of the oxidative phosphorylation machinery. Dysfunction of mitochondrial protein biosynthesis leads to human diseases and plays an important role in the altered metabolism of cancer cells. Recent developments in cryo-electron microscopy enabled the structural characterization of complete yeast and mammalian mitoribosomes at near-atomic resolution. Despite originating from ancestral bacterial ribosomes, mitoribosomes have diverged in their composition and architecture...
January 15, 2018: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/29347788/particle-transport-across-a-channel-via-an-oscillating-potential
#16
Yizhou Tan, Jannes Gladrow, Ulrich F Keyser, Leonardo Dagdug, Stefano Pagliara
Membrane protein transporters alternate their substrate-binding sites between the extracellular and cytosolic side of the membrane according to the alternating access mechanism. Inspired by this intriguing mechanism devised by nature, we study particle transport through a channel coupled with an energy well that oscillates its position between the two entrances of the channel. We optimize particle transport across the channel by adjusting the oscillation frequency. At the optimal oscillation frequency, the translocation rate through the channel is a hundred times higher with respect to free diffusion across the channel...
November 2017: Physical Review. E
https://www.readbyqxmd.com/read/29347346/elucidating-distinct-ion-channel-populations-on-the-surface-of-hippocampal-neurons-via-single-particle-tracking-recurrence-analysis
#17
Grzegorz Sikora, Agnieszka Wyłomańska, Janusz Gajda, Laura Solé, Elizabeth J Akin, Michael M Tamkun, Diego Krapf
Protein and lipid nanodomains are prevalent on the surface of mammalian cells. In particular, it has been recently recognized that ion channels assemble into surface nanoclusters in the soma of cultured neurons. However, the interactions of these molecules with surface nanodomains display a considerable degree of heterogeneity. Here, we investigate this heterogeneity and develop statistical tools based on the recurrence of individual trajectories to identify subpopulations within ion channels in the neuronal surface...
December 2017: Physical Review. E
https://www.readbyqxmd.com/read/29346730/2d-spectroscopy-is-being-used-to-address-core-scientific-questions-in-biology-and-materials-science
#18
Megan Petti, Justin P Lomont, Michał Maj, Martin T Zanni
Two-dimensional spectroscopy is a powerful tool for extracting structural and dynamic information from a wide range of chemical systems. We provide a brief overview of the ways in which two-dimensional visible and infrared spectroscopies are being applied to elucidate fundamental details of important processes in biological and materials science. The topics covered include amyloid proteins, photo-synthetic complexes, ion channels, photovoltaics, batteries, as well as a variety of promising new methods in two-dimensional spectroscopy...
January 18, 2018: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29346439/interspecies-diversity-of-chloride-channel-regulators-calcium-activated-3-genes
#19
Lars Mundhenk, Nancy A Erickson, Nikolai Klymiuk, Achim D Gruber
Members of the chloride channel regulators, calcium-activated (CLCA) family, have been implicated in diverse biomedical conditions, including chronic inflammatory airway diseases such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis, the activation of macrophages, and the growth and metastatic spread of tumor cells. Several observations, however, could not be repeated across species boundaries and increasing evidence suggests that select CLCA genes are particularly prone to dynamic species-specific evolvements...
2018: PloS One
https://www.readbyqxmd.com/read/29345130/two-marine-cyanobacterial-aplysiatoxin-polyketides-neo-debromoaplysiatoxin-a-and-b-with-k-channel-inhibition-activity
#20
Bing-Nan Han, Ting-Ting Liang, Lawrence Jordan Keen, Ting-Ting Fan, Xiao-Dan Zhang, Lin Xu, Qi Zhao, Shu-Ping Wang, Hou-Wen Lin
The isolation and structure elucidation of two cyanobacterial debromoaplysiatoxin (DAT) analogues, neo-debromoaplysiatoxin A (1) and neo-debromoaplysiatoxin B (2), were reported and found to possess 6/10/6 and 6/6/6 fused-ring systems, respectively, which are rarely seen among aplysiatoxins. Both compounds exhibited potent blocking activity against Kv1.5 with IC50 values of 6.94 ± 0.26 and 0.30 ± 0.05 μM, respectively. These findings suggest the potential of aplysiatoxin analogues in modulating ionic channels and also provide links between the DAT target, protein kinase C, and cell regulation...
January 18, 2018: Organic Letters
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