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Calcium channels

Kyoung Hee Seo, Sun-Young Jung, Yeonsun Jin, Sung Hoon Lee
AIMS: Anoctamin-1 (TMEM16A) is a calcium-activated chloride channel that is involved in numerous physiological conditions. Its role has been identified in electrophysiological and histological studies of genetic knockout animals. Recent cellular localization studies have shown that anoctamin-1 is co-expressed with presynaptic proteins, therefore its role in presynaptic terminals has been suggested. However, behavioral studies are lacking because conventional knockouts of anoctamin-1 are lethal after birth...
June 18, 2018: Life Sciences
Lu Zhang, Cuihua Feng, Yamin Zhou, Qiong Zhou
The present study aimed to identify bladder cancer-associated microRNAs (miRNAs) and target genes, and further analyze the potential molecular mechanisms involved in bladder cancer. The mRNA and miRNA expression profiling dataset GSE40355 was downloaded from the Gene Expression Omnibus database. The Limma package in R was used to identify differential expression levels. The Human microRNA Disease Database was used to identify bladder cancer-associated miRNAs and Target prediction programs were used to screen for miRNA target genes...
June 2018: Oncology Letters
Katarzyna Niemirowicz-Laskowska, Katarzyna Głuszek, Ewelina Piktel, Karlis Pajuste, Bonita Durnaś, Grzegorz Król, Agnieszka Z Wilczewska, Paul A Janmey, Aiva Plotniece, Robert Bucki
Background: 1,4-Dihydropyridine (1,4-DHP) and its derivatives are well-known calcium channel blockers with antiarrhythmic and antihypertensive activities. These compounds exhibit pleiotropic effects including antimicrobial activities that rely on their positive charge and amphipathic nature. Use of magnetic nanoparticles (MNPs) as carriers of 1,4-DHP modulates their properties and enables improved formulations with higher efficacy and less toxicity. Methods: In this study, the antimicrobial and immunomodulatory activities of novel 1,4-DHP derivatives in free form and immobilized on MNPs were determined by evaluating pathogen outgrowth and proinflammatory cytokine release in experimental settings that involve incubation of various 1,4-DHPs with clinical isolates of bacteria or fungi as well as mammalian cell culture models...
2018: International Journal of Nanomedicine
Adina Vultur, Christine S Gibhardt, Hedwig Stanisz, Ivan Bogeski
The important role of mitochondria in cancer biology is gaining momentum. With their regulation of cell survival, metabolism, basic cell building blocks, and immunity, among other functions, mitochondria affect not only cancer progression but also the response and resistance to current treatments. Calcium ions are constantly shuttled in and out of mitochondria; thus, playing an important role in the regulation of various cellular processes. The mitochondrial calcium uniporter (MCU) channel and its associated regulators transport calcium across the inner mitochondrial membrane to the mitochondrial matrix...
June 21, 2018: Pflügers Archiv: European Journal of Physiology
La-Mei Wang, Na Tang, Hua Zhong, Li-Juan Pang, Chun-Jun Zhang, Fang He
The present study was to investigate the role of the interaction between canonical transient receptor potential channel 1 (TRPC1) and calcium release-activated calcium modulator 1 (Orai1) in extracellular Ca2+ -sensing receptor (CaR)-induced extracellular Ca2+ influx and nitric oxide (NO) production. Human umbilical vein endothelial cells (HUVECs) were incubated with CaR agonist Spermine [activating store-operated calcium channels (SOC) and receptor-operated calcium channels (ROC)] alone or in combination with the following reagents: CaR negative allosteric modulator Calhex231 plus ROC analogue TPA (activating ROC and blocking SOC), Ro31-8220 (PKC inhibitor that activates SOC and blocks ROC) or Go6967 (PKCs and PKCµ inhibitor that activates SOC and blocks ROC)...
June 25, 2018: Sheng Li Xue Bao: [Acta Physiologica Sinica]
Katherine A White, Vicki J Swier, Jacob T Cain, Jordan L Kohlmeyer, David K Meyerholz, Munir R Tanas, Johanna Uthoff, Emily Hammond, Hua Li, Frank A Rohret, Adam Goeken, Chun-Hung Chan, Mariah R Leidinger, Shaikamjad Umesalma, Margaret R Wallace, Rebecca D Dodd, Karin Panzer, Amy H Tang, Benjamin W Darbro, Aubin Moutal, Song Cai, Wennan Li, Shreya S Bellampalli, Rajesh Khanna, Christopher S Rogers, Jessica C Sieren, Dawn E Quelle, Jill M Weimer
Loss of the NF1 tumor suppressor gene causes the autosomal dominant condition, neurofibromatosis type 1 (NF1). Children and adults with NF1 suffer from pathologies including benign and malignant tumors to cognitive deficits, seizures, growth abnormalities, and peripheral neuropathies. NF1 encodes neurofibromin, a Ras-GTPase activating protein, and NF1 mutations result in hyperactivated Ras signaling in patients. Existing NF1 mutant mice mimic individual aspects of NF1, but none comprehensively models the disease...
June 21, 2018: JCI Insight
Sang-Ho Jo, Sung-Ji Park, Eung Ju Kim, Soo-Joong Kim, Hyun-Jae Cho, Jong-Min Song, Jinho Shin, Jin Joo Park, Joon-Han Shin, Kyoo-Rok Han, Dong-Ju Choi
BACKGROUND: The efficacy of a combination of a calcium channel blocker (CCB) plus chlorthalidone (diuretic) versus a CCB plus an angiotensin receptor blocker (ARB) in patients not responding to CCB monotherapy has not been evaluated previously. We plan to compare the efficacy and safety of S-amlodipine (CCB) plus chlorthalidone versus S-amlodipine plus telmisartan (ARB) combinations among hypertension patients unresponsive to amlodipine monotherapy. METHODS/DESIGN: This study is a prospective, randomized, double-blind, multicenter, parallel, non-inferiority phase 4 study...
June 20, 2018: Trials
M Carreón-Garcidueñas, D Godínez-Hernández, N Alvarado-Gómez, L F Ortega-Varela, C Cervantes-Durán, M Y Gauthereau-Torres
Inhaling solvents can lead to occurrence of cardiac arrhythmias and sudden sniffing death. Mechanisms related to this phenomenon are not fully understood. The purpose of this study was to investigate the effect of acute toluene exposure on heart reactivity to epinephrine and the participation of voltage-gated sodium and calcium channels. We found that acute toluene exposure increased perfusion pressure, left ventricular developed pressure, and heart rate. These actions were inhibited by lidocaine and nifedipine...
June 21, 2018: Toxicology Mechanisms and Methods
Andrea Saponaro, Francesca Cantini, Alessandro Porro, Annalisa Bucchi, Dario DiFrancesco, Vincenzo Maione, Chiara Donadoni, Bianca Introini, Pietro Mesirca, Matteo Elia Mangoni, Gerhard Thiel, Lucia Banci, Bina Santoro, Anna Moroni
Binding of TRIP8b to the cyclic nucleotide binding domain (CNBD) of mammalian HCN channels prevents their regulation by cAMP. Since TRIP8b is expressed exclusively in the brain, we envisage that it can be used for orthogonal control of HCN channels beyond the central nervous system. To this end, we have identified by rational design a 40-aa long peptide (TRIP8bnano ) that recapitulates affinity and gating effects of TRIP8b in HCN isoforms (human hHCN1, mHCn2, rbHCN4) and in the cardiac current If in rabbit and mouse sinoatrial node cardiomyocytes...
June 20, 2018: ELife
A V Shalygin, M A Ryazantseva, L N Glushankova, K O Gusev, D O Kolesnikov, V A Vigont, A Yu Skopin, K V Skobeleva, E V Kaznacheeva
Store-operated channels activated in response to intracellular calcium store depletion represent the main pathway of calcium entry from the extracellular space in nonelectroexcitable cells. Adapter proteins organize the components of this system into integral complex. We studied the influence of adapter proteins of the Homer family on endogenous store-operated calcium Imin channels in A431 cells. Monomeric Homer 1a proteins increase activity of Imin channels, but did not modulate their electrophysiological properties...
June 19, 2018: Bulletin of Experimental Biology and Medicine
Nina Simonovic, Vladimir Jakovljevic, Jovana Jeremic, Zarko Finderle, Ivan Srejovic, Tamara Nikolic Turnic, Isidora Milosavljevic, Vladimir Zivkovic
The aim of this study was to examine and compare the effects of the acute administration of verapamil or amlodipine as representatives of the calcium channel blockers or nicorandil as a representative of the mitochondrial ATP-dependent potassium (KATP ) channel opener to cardiac contractility, coronary flow, and oxidative stress markers on ischemia/reperfusion injury in the isolated rat heart. The hearts of adult male Wistar albino rats (n = 60 total, 12 per group) were divided into five groups, two controls (preconditioning with Krebs-Henseleit solution) and three experimental depending on acute administrated pharmacological agents (0,63 µmol/L of verapamil, 0,1 µmol/L of amlodipine, and 200 µmol/L of nicorandil)...
June 19, 2018: Molecular and Cellular Biochemistry
Lasse Skibsbye, Anne K Bengaard, A M Uldum-Nielsen, Kim Boddum, Torsten Christ, Thomas Jespersen
Sympathetic and vagal activation is linked to atrial arrhythmogenesis. Here we investigated the small conductance Ca2+ -activated K+ (SK)-channel pore-blocker N -(pyridin-2-yl)-4-(pyridine-2-yl)thiazol-2-amine (ICA) on action potential (AP) and atrial fibrillation (AF) parameters in isolated rat atria during β-adrenergic [isoprenaline (ISO)] and muscarinic M2 [carbachol (CCh)] activation. Furthermore, antiarrhythmic efficacy of ICA was benchmarked toward the class-IC antiarrhythmic drug flecainide (Fleca)...
2018: Frontiers in Physiology
Wei-Ming Liao, Jian-Hua Zhang, Shao-Yun Yin, He Lin, Xingmin Zhang, Jihong Wang, Hai-Ping Wang, Kai Wu, Zheng Wang, Ya-Nan Fan, Mei Pan, Cheng-Yong Su
Two-dimensional (2D) metal-organic frameworks have exhibited a range of fascinating attributes, of interest to numerous fields. Here, a calcium-based metal-organic framework with a 2D layered structure has been designed. Dual emissions relating to intralayer excimers and interlayer trapped excitons are produced, showing excitation-dependent shifting tendency, characteristic of a low dimensional semiconductor nature. Furthermore, the layer stacking by weak van der Waals forces among dynamically coordinated DMF molecules enables exfoliation and morphology transformation, which can be achieved by ultrasound in different ratios of DMF/H2 O solvents, or grinding under appropriate humidity conditions, leading to nano samples including ultrathin nanosheets with single or few coordination layers...
June 19, 2018: Nature Communications
Srinivasan Ramakrishnan, Roberto Docampo
Calcium ion (Ca2+ ) serves as a second messenger for a variety of cell functions in trypanosomes. Several proteins in the plasma membrane, acidocalcisomes, endoplasmic reticulum, and mitochondria are involved in its homeostasis and in cell signaling roles. The plasma membrane has a Ca2+ channel for its uptake and a plasma membrane-type Ca2+ -ATPase (PMCA) for its efflux. A similar PMCA is also located in acidocalcisomes, acidic organelles that are the primary Ca2+ store and that possess an inositol 1,4,5-trisphosphate receptor (IP₃R) for Ca2+ efflux...
June 19, 2018: Genes
Huijie Ma 马会杰, Shao-Rui Chen 陈少瑞, Hong Chen 陈红, Lingyong Li 李令勇, De-Pei Li 李德培李德培, Jing-Jing Zhou 周京京, Hui-Lin Pan 潘惠麟
Both the sympathetic nervous system and renin-angiotensin system are critically involved in hypertension development. Although angiotensin II (Ang II) stimulates hypothalamic paraventricular nucleus (PVN) neurons to increase sympathetic vasomotor tone, the molecular mechanism mediating this action remains unclear. The glutamate N -methyl- D -aspartate receptor (NMDAR) in the PVN controls sympathetic outflow in hypertension. In this study, we determined the interaction between α2δ-1 (encoded by Cacna2d1 ), commonly known as a Ca2+ channel subunit, and NMDARs in the hypothalamus and its role in Ang II-induced synaptic NMDAR activity in PVN presympathetic neurons...
June 19, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Ramin Raouf, Stéphane Lolignier, Jane E Sexton, Queensta Millet, Sonia Santana-Varela, Anna Biller, Alice M Fuller, Vanessa Pereira, Jyoti S Choudhary, Mark O Collins, Stephen E Moss, Richard Lewis, Julie Tordo, Els Henckaerts, Michael Linden, John N Wood
Mechanically activated, slowly adapting currents in sensory neurons have been linked to noxious mechanosensation. The conotoxin NMB-1 (noxious mechanosensation blocker-1) blocks such currents and inhibits mechanical pain. Using a biotinylated form of NMB-1 in mass spectrometry analysis, we identified 67 binding proteins in sensory neurons and a sensory neuron-derived cell line, of which the top candidate was annexin A6, a membrane-associated calcium-binding protein. Annexin A6-deficient mice showed increased sensitivity to mechanical stimuli...
June 19, 2018: Science Signaling
Annette D Rieg, Said Suleiman, Carolin Anker, Eva Verjans, Rolf Rossaint, Stefan Uhlig, Christian Martin
BACKGROUND: Platelet-derived growth factor (PDGF)-BB and its receptor PDGFR are highly expressed in pulmonary hypertension (PH) and mediate proliferation. Recently, we showed that PDGF-BB contracts pulmonary veins (PVs) and that this contraction is prevented by inhibition of PDGFR-β (imatinib/SU6668). Here, we studied PDGF-BB-induced contraction and downstream-signalling in isolated perfused lungs (IPL) and precision-cut lung slices (PCLS) of guinea pigs (GPs). METHODS: In IPLs, PDGF-BB was perfused after or without pre-treatment with imatinib (perfused/nebulised), the effects on the pulmonary arterial pressure (PPA ), the left atrial pressure (PLA ) and the capillary pressure (Pcap ) were studied and the precapillary (Rpre ) and postcapillary resistance (Rpost ) were calculated...
June 19, 2018: Respiratory Research
Yun Shi, Yong Wang, Huafeng Wei
Dantrolene, a ryanodine receptor antagonist, is primarily known as the only clinically acceptable and effective treatment for malignant hyperthermia (MH). Inhibition of ryanodine receptor (RyR) by dantrolene decrease the abnormal calcium release from the sarcoplasmic reticulum (SR) or endoplasmic reticulum (ER), where RyR is located on. Recently, emerging researchs on dissociated cells, brains slices, live animal models and patients demonstrate that altered RyR expression and function can also play a vital role in the pathogenesis of Alzheimer's disease (AD)...
June 19, 2018: CNS & Neurological Disorders Drug Targets
Erin M Leonard, Ryan Belowitz, Pieter Agema, Michael J O'Donnell
Chironomids are often one of the dominant organisms in significantly polluted freshwater. Many invertebrate studies have characterized whole organism mechanisms of toxicity, for example, assessing cadmium (Cd) uptake via calcium (Ca) channels. However, with the use of the Scanning Ion-selective Electrode Technique (SIET) and the use of an innovative Cd-selective microelectrode, we analyze this relationship at the organ level using a realistic concentration of Cd and Ca in the hemolymph (blood). Generally, Cd fluxes follow the same directional pattern as Ca, although Ca fluxes are ∼5x higher than those of Cd...
June 19, 2018: Environmental Toxicology and Chemistry
Qian-Ru Zhao, Jun-Mei Lu, Zhao-Yang Li, Yan-Ai Mei
Neuritin is a neurotrophic factor that is activated by neural activity and neurotrophins. Its major function is to promote neurite growth and branching; however, the underlying mechanisms are not fully understood. To address this issue, the present study investigated the effects of neuritin on neurite and spine growth and intracellular Ca2+ concentration in rat cerebellar granule neurons (CGNs). Incubation of CGNs for 24 h with neuritin increased neurite length and spine density; this effect was mimicked by insulin and abolished by inhibiting insulin receptor (IR) or mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) activity...
June 19, 2018: Journal of Neurochemistry
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