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https://www.readbyqxmd.com/read/28572509/dynamic-distinctions-in-the-sodium-calcium-exchanger-adopting-the-inward-and-outward-facing-conformational-states
#1
Moshe Giladi, Liat van Dijk, Bosmat Refaeli, Lior Almagor, Reuben Hiller, Petr Man, Eric Forest, Daniel Khananshvili
Na(+)/Ca(2+) exchanger (NCX) proteins operate through the alternating access mechanism, where the ion-binding pocket is exposed in succession either to the extracellular or the intracellular face of the membrane. The archaeal NCX_Mj (Methanococcus jannaschii NCX) system was used to resolve the backbone dynamics in the inward facing (IF) and outward-facing (OF) states by analyzing purified preparations of apo and ion-bound forms of NCX_Mj-WT and its mutant, NCX_Mj-5L6-8. First, the exposure of extracellular and cytosolic vestibules to the bulk phase was evaluated as the reactivity of single cysteine-mutants to a fluorescent probe, verifying that NCX_Mj-WT and NCX_Mj-5L6-8 preferentially adopt the OF and IF states, respectively...
June 1, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28566634/effect-of-docosahexaenoic-acid-on-voltage-independent-ca-2-entry-pathways-in-cultured-vascular-smooth-muscle-cells-stimulated-with-5-hydroxytryptamine
#2
Takuji Machida, Akina Onoguchi, Kenji Iizuka, Sayuri Ishibashi, Mikiko Yutani, Masahiko Hirafuji
We previously reported that docosahexaenoic acid (DHA) inhibits an increase in intracellular Ca(2+) concentration ([Ca(2+)]i) in cultured rat vascular smooth muscle cells (VSMCs) through a mechanism involving mainly voltage-dependent Ca(2+) channels; however, the effect of DHA on voltage-independent pathways, such as store-operated and receptor-operated Ca(2+) entry, and Ca(2+) entry through Na(+)/Ca(2+) exchanger (NCX), has not been clarified. In the present study, we investigated the effect of DHA treatment on the expression of transient receptor potential canonical (TRPC) channels, capacitative Ca(2+) entry, and Ca(2+) entry through NCX in rat cultured VSMCs stimulated with 5-hydroxytryptamine (5-HT)...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28558076/functional-effects-of-hyperthyroidism-on-cardiac-papillary-muscle-in-rats
#3
Fabricio Furtado Vieira, Robson Ruiz Olivoto, Priscyla Oliveira da Silva, Julio Cesar Francisco, Rosalvo Tadeu Hochmuller Fogaça
BACKGROUND: Hyperthyroidism is currently recognized to affect the cardiovascular system, leading to a series of molecular and functional changes. However, little is known about the functional influence of hyperthyroidism in the regulation of cytoplasmic calcium and on the sodium/calcium exchanger (NCX) in the cardiac muscle. OBJECTIVES: To evaluate the functional changes in papillary muscles isolated from animals with induced hyperthyroidism. METHODS: We divided 36 Wistar rats into a group of controls and another of animals with hyperthyroidism induced by intraperitoneal T3 injection...
December 2016: Arquivos Brasileiros de Cardiologia
https://www.readbyqxmd.com/read/28551786/mitochondrial-bioenergetics-during-ischemia-and-reperfusion
#4
Alicia E Consolini, María I Ragone, Patricia Bonazzola, Germán A Colareda
During ischemia and reperfusion (I/R) mitochondria suffer a deficiency to supply the cardiomyocyte with chemical energy, but also contribute to the cytosolic ionic alterations especially of Ca(2+). Their free calcium concentration ([Ca(2+)]m) mainly depends on mitochondrial entrance through the uniporter (UCam) and extrusion in exchange with Na(+) (mNCX) driven by the electrochemical gradient (ΔΨm). Cardiac energetic is frequently estimated by the oxygen consumption, which determines metabolism coupled to ATP production and to the maintaining of ΔΨm...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28535874/coupling-between-the-trpc3-ion-channel-and-the-ncx1-transporter-contributed-to-vegf-induced-erk1-2-activation-and-angiogenesis-in-human-primary-endothelial-cells
#5
Petros Andrikopoulos, Suzanne A Eccles, Muhammad M Yaqoob
It has been previously demonstrated that the bi-directional transporter Na(+)/Ca(2+) exchanger (NCX) working in the reverse (Ca(2+)-influx) - mode promotes the activation of ERK1/2 in response to the key pro-angiogenic cytokine VEGF in human endothelial cells (ECs). However, the molecular event(s) that elicit NCX reversal in VEGF-stimulated ECs remain unclear. Here we investigated whether Na(+) influx via the diacylglycerol (DAG) - activated non-selective cation channel TRPC3 was functionally associated with NCX and whether its activity was required for VEGF-induced ERK1/2 activation and angiogenesis...
May 20, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28534960/cellular-na-handling-mechanisms-involved-in-airway-smooth-muscle-contraction-review
#6
Bettina Sommer, Edgar Flores-Soto, Georgina Gonzalez-Avila
A decrease in bronchial diameter is designated as bronchoconstriction (BC) and impedes the flow of air through the airway. Asthma is characterized by inflammation of the airways, reversible BC and nonspecific hyperreactivity. These last two symptoms are dependent on airway smooth muscle. Stimuli that trigger contraction can be characterized as chemical (neurotransmitters, cytokines and terpenoids) and physical (volume inspired, air pressure). Both stimuli activate signaling pathways by acting on membrane proteins and facilitating the passage of ions through the membrane, generating a voltage change and a subsequent depolarization...
May 17, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28529049/heterogeneity-of-transverse-axial-tubule-system-in-mouse-atria-remodeling-in-atrial-specific-na-ca-2-exchanger-knockout-mice
#7
Xin Yue, Rui Zhang, Brian Kim, Aiqun Ma, Kenneth D Philipson, Joshua I Goldhaber
Transverse-axial tubules (TATs) are commonly assumed to be sparse or absent in atrial myocytes from small animals. Atrial myocytes from rats, cats and rabbits lack TATs, which results in a characteristic "V"-shaped Ca release pattern in confocal line-scan recordings due to the delayed rise of Ca in the center of the cell. To examine TAT expression in isolated mouse atrial myocytes, we loaded them with the membrane dye Di-4-ANEPPS to label TATs. We found that >80% of atrial myocytes had identifiable TATs...
May 19, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28506097/a-computational-model-of-the-ca-2-transients-and-influence-of-buffering-in-guinea-pig-urinary-bladder-smooth-muscle-cells
#8
Vijay Dave, Rohit Manchanda
Many cellular events including electrical activity and muscle contraction are regulated and coordinated by intracellular [Formula: see text] concentration ([[Formula: see text]][Formula: see text]. In detrusor smooth muscle (DSM) cells, [[Formula: see text]]i is normally maintained at very low levels and rises transiently during signalling processes as a result of (i) influx from the extracellular space (mainly via L-type and T-type [Formula: see text] channels) and (ii) [Formula: see text] release from sarcoplasmic reticulum (SR) into the cytoplasm...
April 20, 2017: Journal of Bioinformatics and Computational Biology
https://www.readbyqxmd.com/read/28497275/na-ca-2-exchangers-and-orai-channels-jointly-refill-endoplasmic-reticulum-er-ca-2-via-er-nanojunctions-in-vascular-endothelial-cells
#9
Cristiana M L Di Giuro, Niroj Shrestha, Roland Malli, Klaus Groschner, Cornelis van Breemen, Nicola Fameli
We investigated the role of Na(+)/ Ca(2+) exchange (NCX) in the refilling of endoplasmic reticulum (ER) Ca(2+) in vascular endothelial cells under various conditions of cell stimulation and plasma membrane (PM) polarization. Better understanding of the mechanisms behind basic ER Ca(2+) content regulation is important, since current hypotheses on the possible ultimate causes of ER stress point to deterioration of the Ca(2+) transport mechanism to/from ER itself. We measured [Ca(2+)]i temporal changes by Fura-2 fluorescence under experimental protocols that inhibit a host of transporters (NCX, Orai, non-selective transient receptor potential canonical (TRPC) channels, sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA), Na(+)/ K(+) ATPase (NKA)) involved in the Ca(2+) communication between the extracellular space and the ER...
May 11, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28495655/increased-sodium-calcium-exchanger-activity-enhances-beta-adrenergic-mediated-increase-in-heart-rate-whole-heart-study-in-a-homozygous-sodium-calcium-exchanger-overexpressor-mouse-model
#10
Sven Kaese, Nils Bögeholz, Paul Pauls, Dirk Dechering, Jan Olligs, Katharina Kölker, Sascha Badawi, Gerrit Frommeyer, Christian Pott, Lars Eckardt
BACKGROUND: The cardiac sodium/calcium (Na(+)/Ca(2+)) exchanger (NCX) contributes to diastolic depolarization in cardiac pacemaker cells. Increased NCX activity has been found in heart failure and atrial fibrillation. The influence of increased NCX activity on resting heart rate, beta-adrenergic-mediated increase in heart rate, and cardiac conduction properties is unknown. OBJECTIVE: The purpose of this study was to investigate the influence of NCX overexpression in a homozygous transgenic whole-heart mouse model (NCX-OE) on sinus and AV nodal function...
May 8, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/28493889/characterization-of-a-novel-antibiofilm-effect-of-nitric-oxide-releasing-aspirin-ncx-4040-on-candida-albicans-isolates-from-denture-stomatitis-patients
#11
Francisco Madariaga-Venegas, Roberto Fernández-Soto, Luisa Fernanda Duarte, Nicole Suarez, Daniela Delgadillo, José A Jara, Ricardo Fernández-Ramires, Blanca Urzúa, Alfredo Molina-Berríos
Candida albicans biofilms play a key role in denture stomatitis, one of the most common oral pathologies in elderly people. Because biofilms are highly resistant to antifungals, new pharmacological strategies are needed. Aspirin and nitric oxide-donor molecules have both shown antibiofilm effects on C. albicans, making them promising candidates for treatment. In this study, we evaluated the antifungal/antibiofilm effect of a nitric-oxide releasing aspirin (NO-ASA) on C. albicans isolates from denture stomatitis patients in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28487470/discrepant-effects-of-heart-failure-on-electrophysiological%C3%A2-property-in-right-ventricular-outflow-tract-and-left-ventricular-outflow-tract-cardiomyocytes
#12
Yen-Yu Lu, Chen-Chuan Cheng, Chin-Feng Tsai, Yung Kuo Lin, Ting-I Lee, Yao-Chang Chen, Shih-Ann Chen, Yi Jen Chen
Ventricular arrhythmias commonly arise from the right and left ventricular outflow tracts (RVOT/LVOT) in patients without structural heart disease. Heart failure (HF) significantly increases the risk of ventricular arrhythmias. The regional differences and how HF affects the electrophysiological characteristics of RVOT and LVOT cardiomyocytes remain unclear. The whole-cell patch clamp technique was used to investigate the action potentials and ionic currents in isolated single RVOT and LVOT cardiomyocytes from control and rapid ventricular pacing-induced HF rabbit...
May 9, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28476922/sarcolemmal-distribution-of-ica-and-incx-and-ca-autoregulation-in-mouse-ventricular-myocytes
#13
Hanne C Gadeberg, Cherrie H T Kong, Simon M Bryant, Andrew F James, Clive H Orchard
The balance of Ca influx and efflux regulates the Ca load of cardiac myocytes, a process known as autoregulation. Previous work has shown that Ca influx, via L-type Ca current (ICa), and efflux, via Na-Ca exchange (NCX), occur predominantly at t-tubules; however the role of t-tubules in autoregulation is unknown. We therefore investigated the sarcolemmal distribution of ICa and INCX, and autoregulation, in mouse ventricular myocytes using whole cell voltage-clamp and simultaneous Ca measurement in intact and detubulated (DT) cells...
May 5, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28472418/increased-passive-stiffness-promotes-diastolic-dysfunction-despite-improved-ca2-handling-during-left-ventricular-concentric-hypertrophy
#14
Åsmund T Røe, Jan Magnus Aronsen, Kristine Skårdal, Nazha Hamdani, Wolfgang A Linke, Håvard E Danielsen, Ole M Sejersted, Ivar Sjaastad, William E Louch
Aims: Concentric hypertrophy following pressure-overload is linked to preserved systolic function but impaired diastolic function, and is an important substrate for heart failure with preserved ejection fraction. While increased passive stiffness of the myocardium is a suggested mechanism underlying diastolic dysfunction in these hearts, the contribution of a ctive diastolic Ca 2+ cycling in cardiomyocytes remains unclear. In this study, we sought to dissect contributions of passive and active mechanisms to diastolic dysfunction in the concentrically hypertrophied heart following pressure-overload...
May 4, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28435224/investigation-of-triamterene-as-an-inhibitor-of-the-tgr5-receptor-identification-in-cells-and-animals
#15
Yingxiao Li, Kai Chun Cheng, Chiang-Shan Niu, Shih-Hsiang Lo, Juei-Tang Cheng, Ho-Shan Niu
BACKGROUND: G-protein-coupled bile acid receptor 1 (GPBAR1, also known as TGR5) has been shown to participate in glucose homeostasis. In animal models, a TGR5 agonist increases incretin secretion to reduce hyperglycemia. Many agonists have been developed for clinical use. However, the effects of TGR5 blockade have not been studied extensively, with the exception of studies using TGR5 knockout mice. Therefore, we investigated the potential effect of triamterene on TGR5. METHODS: We transfected the TGR5 gene into cultured Chinese hamster ovary cells (CHO-K1 cells) to express TGR5...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28432123/an-amphipathic-%C3%AE-helix-directs-palmitoylation-of-the-large-intracellular-loop-of-the-sodium-calcium-exchanger
#16
Fiona Plain, Samitha Dilini Congreve, Rachel Sue Zhen Yee, Jennifer Kennedy, Jacqueline Howie, Chien-Wen Kuo, Niall Fraser, William Fuller
The electrogenic sodium/calcium exchanger (NCX) mediates bidirectional calcium transport controlled by the transmembrane sodium gradient. NCX inactivation occurs in the absence of phosphatidylinositol 4,5-bisphosphate (PIP2), and is facilitated by palmitoylation of a single cysteine at position 739 within NCX's large intracellular loop. The aim of this investigation was to identify the structural determinants of NCX1 palmitoylation. Full-length NCX1 (FL-NCX1) and a YFP fusion protein of the NCX1 large intracellular loop (YFP-NCX1) were expressed in HEK cells...
April 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28428550/structure-based-dynamic-arrays-in-regulatory-domains-of-sodium-calcium-exchanger-ncx-isoforms
#17
Moshe Giladi, Su Youn Lee, Yarden Ariely, Yotam Teldan, Rotem Granit, Roi Strulovich, Yoni Haitin, Ka Young Chung, Daniel Khananshvili
Mammalian Na(+)/Ca(2+) exchangers, NCX1 and NCX3, generate splice variants, whereas NCX2 does not. The CBD1 and CBD2 domains form a regulatory tandem (CBD12), where Ca(2+) binding to CBD1 activates and Ca(2+) binding to CBD2 (bearing the splicing segment) alleviates the Na(+)-induced inactivation. Here, the NCX2-CBD12, NCX3-CBD12-B, and NCX3-CBD12-AC proteins were analyzed by small-angle X-ray scattering (SAXS) and hydrogen-deuterium exchange mass-spectrometry (HDX-MS) to resolve regulatory variances in the NCX2 and NCX3 variants...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28350969/mechanisms-of-spontaneous-pacing-sinoatrial-nodal-cells-neonatal-cardiomyocytes-and-human-stem-cell-derived-cardiomyocytes
#18
Martin Morad, Xiao-Hua Zhang
The sinoatrial (SA) node is the primary site from which the mammalian heart is paced, but the mechanisms underlying the pacemaking still remain clouded. It is generally believed that the hyperpolarization-activated current If, encoded by hyperpolarization-activated cyclic nucleotide-gated (HCN) genes, contributes significantly to pacing, which in tandem with inward current generated by efflux of Ca(2+) via the Na(+)-Ca(2+) exchanger (NCX), resulting from the released Ca(2+), mediates the diastolic depolarization...
March 28, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28346695/contribution-of-small-conductance-k-channels-to-sinoatrial-node-pacemaker-activity-insights-from-atrial-specific-na-ca-2-exchange-knockout-mice
#19
Angelo G Torrente, Rui Zhang, Heidi Wang, Audrey Zaini, Brian Kim, Xin Yue, Kenneth D Philipson, Joshua I Goldhaber
KEY POINTS: Repolarizing currents through K(+) channels are essential for proper sinoatrial node (SAN) pacemaking, but the influence of intracellular Ca(2+) on repolarization in the SAN is uncertain. We identified all three isoforms of Ca(2+) -activated small conductance K(+) (SK) channels in the murine SAN. SK channel blockade slows repolarization and subsequent depolarization of SAN cells. In the atrial-specific Na(+) /Ca(2+) exchanger (NCX) knockout mouse, cellular Ca(2+) accumulation during spontaneous SAN pacemaker activity produces intermittent hyperactivation of SK channels, leading to arrhythmic pauses alternating with bursts of pacing...
June 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28340146/effect-of-broiler-breeders-fed-with-corn-or-sorghum-diet-and-canthaxanthin-supplementation-on-production-and-reproductive-performance
#20
C E V Bonilla, A P Rosa, A Londero, C B S Giacomini, C Orso, M O Fernandes, S J Paixão, D V Bonamigo
This study was designed to evaluate the effect of corn or sorghum diet and canthaxanthin (CX) supplementation on performance in broiler breeders. A total of 440 females with similar body weight (BW) (3.71 ± 0.14 kg) and 60 roosters were placed in an open-sided house with 20 pens, randomly distributed in a factorial arrangement (2 × 2). There were 4 diets of 2 ingredients; corn (CO) or sorghum (SO) and 2 levels of CX; 6 mg/kg (CX) and 0 mg/kg (NCX) totaling 5 replicate pens of 22 females and 3 males each, from 42 to 65 wk, divided in 2 periods (from wk 42 to 53 and wk 54 to 65)...
June 1, 2017: Poultry Science
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