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https://www.readbyqxmd.com/read/28435224/investigation-of-triamterene-as-an-inhibitor-of-the-tgr5-receptor-identification-in-cells-and-animals
#1
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
#2
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
#3
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-sa-nodal-cells-neonatal-cardiomyocytes-and-human-stem-cell-derived-cardiomyocytes
#4
Martin Morad, Xiaohua Zhang
The sino-atrial 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 I<sub><i>f</i></sub>, encoded by Hyperpolarization-activated cyclic nucleotide-gated (HCN) genes, contributes significantly to pacing, which in tandem with inward current generated by efflux of Ca<sup>2+</sup> via the Na<sup>+</sup>-Ca<sup>2+</sup> exchanger (NCX), resulting from the released Ca<sup>2+</sup>, 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
#5
Angelo G Torrente, Rui Zhang, Heidi Wang, Audrey Zaini, Brian Kim, Xin Yue, Kenneth D Philipson, Joshua I Goldhaber
Small conductance K(+) (SK) channels have been implicated as modulators of spontaneous depolarization and electrical conduction that may be involved in cardiac arrhythmia. However, neither their presence nor their contribution to sinoatrial node (SAN) pacemaker activity have been investigated. Using quantitative PCR (q-PCR), immunostaining and patch clamp recordings of membrane current and voltage, we identified all three SK isoforms (SK1, SK2 and SK3) in mouse SAN. Inhibition of SK channels with the specific blocker apamin prolonged action potentials (APs) in isolated SAN cells...
March 27, 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
#6
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)...
March 4, 2017: Poultry Science
https://www.readbyqxmd.com/read/28327381/the-enhancing-effect-of-a-cation-%C3%AF-interaction-on-the-cooperativity-of-halogen-bonds-a-computational-study
#7
Mehdi D Esrafili, Soheila Asadollahi
In this work, we investigate the effect of a cation-π interaction on the cooperativity of X⋯N halogen bonds in PhX⋯NCX⋯NH3 complexes, where Ph=phenyl and X=Cl, Br, I. Molecular geometries and interaction energies of the resulting complexes are studied at the MP2/aug-cc-pVDZ(-PP) computational level. The mechanism of the cooperativity between halogen bonds is analyzed using parameters derived from the noncovalent index, quantum theory of atoms in molecules and natural bond orbital methodologies. It is found that the divalent cations (Be(2+), Mg(2+)) have a larger influence on the cooperativity of halogen bonds than monovalent ones (Li(+), Na(+))...
May 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28284503/renal-denervation-regulates-the-atrial-arrhythmogenic-substrates-through-reverse-structural-remodeling-in-heart-failure-rabbit-model
#8
Shinya Yamada, Li-Wei Lo, Yu-Hui Chou, Wei-Lun Lin, Shih-Lin Chang, Yenn-Jiang Lin, Shih-Ann Chen
BACKGROUND: Heart failure (HF) causes atrial remodeling and increases the incidence of atrial fibrillation (AF). Renal denervation (RDN) has been shown to decrease the development of AF. This study aimed to identify the effects of RDN on the atrial arrhythmogenic substrates in HF. METHODS: Rabbits were classified into four groups: control (n=9), RDN (n=10), HF (n=6) and HF-RDN (n=9). Surgical and chemical RDN was approached through bilateral retroperitoneal flank incisions in RDN and HF-RDN...
May 15, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28269645/development-of-a-detailed-model-of-calcium-dynamics-at-the-postsynaptic-spine-of-an-excitatory-synapse
#9
Eric Y Hu, Jean-Marie C Bouteiller, Dong Song, Theodore W Berger
Postsynaptic calcium dynamics play a critical role in synaptic plasticity, but are often difficult to measure in experimental protocols due to their relatively fast rise and decay times, and the small spine dimensions. To circumvent these limitations, we propose to develop a computational model of calcium dynamics in the postsynaptic spine. This model integrates the main elements that participate in calcium concentration influx, efflux, diffusion and buffering. These consist of (i) spine geometry; (ii) calcium influx through NMDA receptors and voltage-dependent calcium channels (VDCC); (iii) calcium efflux with plasma membrane calcium pumps (PMCA) and sodium-calcium exchangers (NCX); (iv) intracellular calcium stores; and (v) calcium buffers...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28268302/role-of-cytosolic-calcium-diffusion-in-cardiac-purkinje-cells
#10
Bijay Limbu, Kushal Shah, Makarand Deo
The Cardiac Purkinje cells (PCs) exhibit distinct calcium (Ca2+) homeostasis than that in ventricular myocytes (VMs). Due to lack of t-tubules in PCs, the Ca2+ ions entering the cell have to diffuse through the cytoplasm to reach the sarcoplasmic reticulum (SR) before triggering Ca2+-induced-Ca2+-release (CICR). In recent experimental studies PCs have been shown to be more susceptible to action potential (AP) abnormalities than the VMs, however the exact mechanisms are poorly understood. In this study, we utilize morphologically realistic detailed biophysical mathematical model of a murine PC to systematically examine the role intracellular Ca2+ diffusion in the APs of PCs...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28227903/development-of-a-detailed-model-of-calcium-dynamics-at-the-postsynaptic-spine-of-an-excitatory-synapse
#11
Eric Y Hu, Jean-Marie C Bouteiller, Dong Song, Theodore W Berger, Eric Y Hu, Jean-Marie C Bouteiller, Dong Song, Theodore W Berger, Jean-Marie C Bouteiller, Eric Y Hu, Dong Song, Theodore W Berger
Postsynaptic calcium dynamics play a critical role in synaptic plasticity, but are often difficult to measure in experimental protocols due to their relatively fast rise and decay times, and the small spine dimensions. To circumvent these limitations, we propose to develop a computational model of calcium dynamics in the postsynaptic spine. This model integrates the main elements that participate in calcium concentration influx, efflux, diffusion and buffering. These consist of (i) spine geometry; (ii) calcium influx through NMDA receptors and voltage-dependent calcium channels (VDCC); (iii) calcium efflux with plasma membrane calcium pumps (PMCA) and sodium-calcium exchangers (NCX); (iv) intracellular calcium stores; and (v) calcium buffers...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28226461/role-of-cytosolic-calcium-diffusion-in-cardiac-purkinje-cells
#12
Bijay Limbu, Kushal Shah, Makarand Deo, Bijay Limbu, Kushal Shah, Makarand Deo, Bijay Limbu, Makar Deo, Kushal Shah
The Cardiac Purkinje cells (PCs) exhibit distinct calcium (Ca(2)+) homeostasis than that in ventricular myocytes (VMs). Due to lack of t-tubules in PCs, the Ca(2)+ ions entering the cell have to diffuse through the cytoplasm to reach the sarcoplasmic reticulum (SR) before triggering Ca(2)+-induced-Ca(2)+-release (CICR). In recent experimental studies PCs have been shown to be more susceptible to action potential (AP) abnormalities than the VMs, however the exact mechanisms are poorly understood. In this study, we utilize morphologically realistic detailed biophysical mathematical model of a murine PC to systematically examine the role intracellular Ca(2)+ diffusion in the APs of PCs...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28218221/gene-expressions-underlying-mishandled-calcium-clearance-and-elevated-generation-of-reactive-oxygen-species-in-the-coronary-artery-smooth-muscle-cells-of-chronic-heart-failure-rats
#13
Liang Ding, Xian-Xiu Su, Wen-Hui Zhang, Yu-Xiang Xu, Xue-Feng Pan
BACKGROUND: The calcium clearance and reactive oxygen species (ROS) generations in the coronary artery smooth muscle cells in chronic heart failure (HF) have not been fully investigated. Therefore, we attempted to understand the gene expressions underlying the mishandling of calcium clearance and the accumulations of ROS. METHODS: We initially established an animal model of chronic HF by making the left anterior descending coronary artery ligation (CAL) in rats, and then isolated the coronary artery vascular smooth muscle cells from the ischemic and the nonischemic parts of the coronary artery vessels in 12 weeks after CAL operation...
February 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28212796/sodium-calcium-exchanger-in-pig-coronary-artery
#14
A K Grover
This review focuses on the sodium-calcium exchangers (NCX) in the left anterior descending coronary artery smooth muscle. Bathing tissues in Na(+)-substituted solutions caused them to contract. In cultured smooth muscle cells, it increased the cytosolic Ca(2+) concentration and extracellular entry of (45)Ca(2+). All three activities were attributed to NCX since they were inhibited by NCX inhibitors. The tissues also expressed the sarco/endoplasmic reticulum (SER) Ca(2+) pump SERCA2b whose activity was much greater than that of NCX...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28196860/the-nclx-type-na-ca-2-exchanger-ncx-9-is-required-for-patterning-of-neural-circuits-in-caenorhabditis-elegans
#15
Vishal Sharma, Soumitra Roy, Israel Sekler, Damien M O'Halloran
NCLX is a Na(+)/Ca(2+) exchanger that uses energy stored in the transmembrane sodium gradient to facilitate the exchange of sodium ions for ionic calcium. Mammals have a single NCLX, which has been shown to function primarily at the mitochondrion and is an important regulator of neuronal physiology by contributing to neurotransmission and synaptic plasticity. The role of NCLX in developmental cell patterning (e.g. in neural circuits) is largely unknown. Here we describe a novel role for the Caenorhabditis elegans NCLX-type protein, NCX-9, in neural circuit formation...
March 31, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28195313/neuronal-sodium-channels-emerging-components-of-the-nano-machinery-of-cardiac-calcium-cycling
#16
Rengasayee Veeraraghavan, Sándor Györke, Przemysław B Radwański
Excitation-contraction coupling is the bridge between cardiac electrical activation and mechanical contraction. It is driven by the influx of Ca(2+) across the sarcolemma triggering Ca(2+) release from the sarcoplasmic reticulum (SR) - a process termed Ca(2+) -induced Ca(2+) release (CICR) - followed by re-sequestration of Ca(2+) into the SR. The Na(+) /Ca(2+) exchanger inextricably couples the cycling of Ca(2+) and Na(+) in cardiac myocytes. Thus, influx of Na(+) via voltage-gated Na(+) channels (NaV ) has emerged as an important regulator of CICR both in health and in disease...
February 14, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28162543/-307-increased-ncx-activity-as-a-protective-mechanism-against-chemotherapy-induced-peripheral-neuropathy
#17
E Yilmaz, M Gold
No abstract text is available yet for this article.
April 2016: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28149313/effects-of-digoxin-on-cardiac-iron-content-in-rat-model-of-iron-overload
#18
Hamid Reza Nasri, Beydolah Shahouzehi, Yaser Masoumi-Ardakani, Maryam Iranpour
BACKGROUND: Plasma iron excess can lead to iron accumulation in heart, kidney and liver. Heart failure is a clinical widespread syndrome. In thalassemia, iron overload cardiomyopathy is caused by iron accumulation in the heart that leads to cardiac damage and heart failure. Digoxin increases the intracellular sodium concentration by inhibition of Na+/K+-ATPase that affects Na+/Ca2+ exchanger (NCX), which raises intracellular calcium and thus attenuates heart failure. The mechanism of iron uptake into cardiomyocytes is not exactly understood...
July 2016: ARYA Atherosclerosis
https://www.readbyqxmd.com/read/28132899/pathological-consequences-of-micu1-mutations-on-mitochondrial-calcium-signalling-and-bioenergetics
#19
Gauri Bhosale, Jenny Sharpe, Amanda Koh, Antonina Kouli, Gyorgy Szabadkai, Michael R Duchen
Loss of function mutations of the protein MICU1, a regulator of mitochondrial Ca(2+) uptake, cause a neuronal and muscular disorder characterised by impaired cognition, muscle weakness and an extrapyramidal motor disorder. We have shown previously that MICU1 mutations cause increased resting mitochondrial Ca(2+) concentration ([Ca(2+)]m). We now explore the functional consequences of MICU1 mutations in patient derived fibroblasts in order to clarify the underlying pathophysiology of this disorder. We propose that deregulation of mitochondrial Ca(2+) uptake through loss of MICU1 raises resting [Ca(2+)]m, initiating a futile Ca(2+) cycle, whereby continuous mitochondrial Ca(2+) influx is balanced by Ca(2+) efflux through the sodium calcium exchanger (NLCXm)...
January 26, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28101642/late-sodium-current-and-intracellular-ionic-homeostasis-in-acute-ischemia
#20
Carlotta Ronchi, Eleonora Torre, Riccardo Rizzetto, Joyce Bernardi, Marcella Rocchetti, Antonio Zaza
Blockade of the late Na(+) current (I NaL) protects from ischemia/reperfusion damage; nevertheless, information on changes in I NaL during acute ischemia and their effect on intracellular milieu is missing. I NaL, cytosolic Na(+) and Ca(2+) activities (Nacyt, Cacyt) were measured in isolated rat ventricular myocytes during 7 min of simulated ischemia (ISC); in all the conditions tested, effects consistently exerted by ranolazine (RAN) and tetrodotoxin (TTX) were interpreted as due to I NaL blockade. The results indicate that I NaL was enhanced during ISC in spite of changes in action potential (AP) contour; I NaL significantly contributed to Nacyt rise, but only marginally to Cacyt rise...
March 2017: Basic Research in Cardiology
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