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https://www.readbyqxmd.com/read/29771311/pathobiology-of-cardiac-dyssynchrony-and-resynchronization-therapy
#1
Uyên Châu Nguyên, Nienke J Verzaal, Frans A van Nieuwenhoven, Kevin Vernooy, Frits W Prinzen
Synchronous ventricular electrical activation is a prerequisite for adequate left ventricular (LV) systolic function. Conduction abnormalities such as left bundle branch block, and ventricular pacing lead to a dyssynchronous electrical activation sequence, which may have deleterious consequences. The present review attempts to connect the various processes involved in the development of 'dyssynchronopathy', and its correction by cardiac resynchronization therapy (CRT). Abnormal electrical impulse conduction leads to abnormal contraction, characterized by regional differences in timing as well as shortening patterns and amount of external work performed...
May 15, 2018: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/29730765/control-of-neuronal-ryanodine-receptor-mediated-calcium-signaling-by-calsenilin
#2
Michael A Grillo, Stephanie L Grillo, Bryan C Gerdes, Jacob G Kraus, Peter Koulen
Calsenilin is a calcium ion (Ca2+ )-binding protein involved in regulating the intracellular concentration of Ca2+ , a second messenger that controls multiple cellular signaling pathways. The ryanodine receptor (RyR) amplifies Ca2+ signals entering the cytoplasm by releasing Ca2+ from endoplasmic reticulum (ER) stores, a process termed calcium-induced calcium release (CICR). Here, we describe a novel mechanism, in which calsenilin controls the activity of neuronal RyRs. We show calsenilin co-localized with RyR2 and 3 in the ER of mouse hippocampal and cortical neurons using immunocytochemistry...
May 5, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29664963/trpv4-inhibition-attenuates-stretch-induced-inflammatory-cellular-responses-and-lung-barrier-dysfunction-during-mechanical-ventilation
#3
N Pairet, S Mang, G Fois, M Keck, M Kühnbach, J Gindele, M Frick, P Dietl, D J Lamb
Mechanical ventilation is an important tool for supporting critically ill patients but may also exert pathological forces on lung cells leading to Ventilator-Induced Lung Injury (VILI). We hypothesised that inhibition of the force-sensitive transient receptor potential vanilloid (TRPV4) ion channel may attenuate the negative effects of mechanical ventilation. Mechanical stretch increased intracellular Ca2+ influx and induced release of pro-inflammatory cytokines in lung epithelial cells that was partially blocked by about 30% with the selective TRPV4 inhibitor GSK2193874, but nearly completely blocked with the pan-calcium channel blocker ruthenium red, suggesting the involvement of more than one calcium channel in the response to mechanical stress...
2018: PloS One
https://www.readbyqxmd.com/read/29554088/kca3-1-ion-channel-a-novel-therapeutic-target-for-corneal-fibrosis
#4
Govindaraj Anumanthan, Suneel Gupta, Michael K Fink, Nathan P Hesemann, Douglas K Bowles, Lindsey M McDaniel, Maaz Muhammad, Rajiv R Mohan
Vision impairment from corneal fibrosis is a common consequence of irregular corneal wound healing after injury. Intermediate-conductance calmodulin/calcium-activated K+ channels 3.1 (KCa3.1) play an important role in cell cycle progression and cellular proliferation. Proliferation and differentiation of corneal fibroblasts to myofibroblasts can lead to corneal fibrosis after injury. KCa3.1 has been shown in many non-ocular tissues to promote fibrosis, but its role in corneal fibrosis is still unknown. In this study, we characterized the expression KCa3...
2018: PloS One
https://www.readbyqxmd.com/read/29496495/assessment-of-the-trpm8-inhibitor-amtb-in-breast-cancer-cells-and-its-identification-as-an-inhibitor-of-voltage-gated-sodium-channels
#5
Kunsala T D S Yapa, Jennifer Deuis, Amelia A Peters, Paraic A Kenny, Sarah J Roberts-Thomson, Irina Vetter, Gregory R Monteith
AIMS: To assess levels of the calcium permeable transient receptor potential cation channel, subfamily melastatin, member 8 (TRPM8) in breast cancer molecular subtypes and to assess the consequences of TRPM8 pharmacological inhibition with AMTB (an inhibitor of TRPM8) on breast cancer cell lines. MATERIALS AND METHODS: Cell viability and migration of breast cancer cells was determined using MTS assays and wound healing assays, respectively. RNA-Seq analysis of breast tumours and qPCR in breast cancer cell lines were used to assess mRNA levels of ion channels...
April 1, 2018: Life Sciences
https://www.readbyqxmd.com/read/29473171/nimodipine-confers-clinical-improvement-in-two-models-of-experimental-autoimmune-encephalomyelitis
#6
Jens Ingwersen, Lorenzo De Santi, Britta Wingerath, Jonas Graf, Barbara Koop, Reiner Schneider, Christina Hecker, Friederike Schröter, Mary Bayer, Anna Dorothee Engelke, Michael Dietrich, Philipp Albrecht, Hans-Peter Hartung, Pasquale Annunziata, Orhan Aktas, Tim Prozorovski
Multiple sclerosis (MS) is characterized by inflammatory neurodegeneration, with axonal injury and neuronal cell death occurring in parallel to demyelination. Regarding the molecular mechanisms responsible for demyelination and axonopathy, energy failure, aberrant expression of ion channels and excitotoxicity have been suggested to lead to Ca2+ overload and subsequent activation of calcium-dependent damage pathways. Thus, the inhibition of Ca2+ influx by pharmacological modulation of Ca2+ channels may represent a novel neuroprotective strategy in the treatment of secondary axonopathy...
February 23, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29452304/the-chondrocyte-channelome-a-narrative-review
#7
Ali Mobasheri, Csaba Matta, Ilona Uzielienè, Emma Budd, Pablo Martín-Vasallo, Eiva Bernotiene
Chondrocytes are the main cells in the extracellular matrix (ECM) of articular cartilage and possess a highly differentiated phenotype that is the hallmark of the unique physiological functions of this specialised load-bearing connective tissue. The plasma membrane of articular chondrocytes contains a rich and diverse complement of membrane proteins, known as the membranome, which defines the cell surface phenotype of the cells. The membranome is a key target of pharmacological agents and is important for chondrocyte function...
February 13, 2018: Joint, Bone, Spine: Revue du Rhumatisme
https://www.readbyqxmd.com/read/29430647/the-cells-and-conductance-mediating-cholinergic-neurotransmission-in-the-murine-proximal-stomach
#8
Tae Sik Sung, Sung Jin Hwang, Sang Don Koh, Yulia Bayguinov, Lauen E Peri, Peter J Blair, Timothy I Webb, David M Pardo, Jason R Rock, Kenton M Sanders, Sean M Ward
KEY POINTS: Enteric neurotransmission is essential for gastrointestinal (GI) motility, although the cells and conductances responsible for post-junctional responses are controversial. The calcium-activated chloride conductance (CaCC), anoctamin-1 (Ano1), was expressed by intramuscular interstitial cells of Cajal (ICC-IM) in proximal stomach and not resolved in smooth muscle cells (SMCs). Cholinergic nerve fibres were closely apposed to ICC-IM. Conductances activated by cholinergic stimulation in isolated ICC-IM and SMCs were determined...
May 1, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29316407/a-thallium-based-screening-procedure-to-identify-molecules-that-modulate-the-activity-of-ca-2-activated-monovalent-cation-selective-channels
#9
Koenraad Philippaert, Sara Kerselaers, Thomas Voets, Rudi Vennekens
TRPM5 functions as a calcium-activated monovalent cation-selective ion channel and is expressed in a variety of cell types. Dysfunction of this type of channel has been recently implied in cardiac arrhythmias, diabetes, and other pathologies. Therefore, a growing interest has emerged to develop the pharmacology of these ion channels. We optimized a screening assay based on the thallium flux through the TRPM5 channel and a fluorescent thallium dye as a probe for channel activity. We show that this assay is capable of identifying molecules that inhibit or potentiate calcium-activated monovalent cation-selective ion channels...
April 2018: SLAS Discovery
https://www.readbyqxmd.com/read/29193257/fundamental-structural-and-functional-properties-of-aquaporin-ion-channels-found-across-the-kingdoms-of-life
#10
Mohamad Kourghi, Jinxin V Pei, Michael L De Ieso, Saeed Nourmohammadi, Pak Hin Chow, Andrea J Yool
Aquaporin (AQP) channels in the major intrinsic protein (MIP) family are known to facilitate transmembrane water fluxes in prokaryotes and eukaryotes. Some classes of AQPs also conduct ions, glycerol, urea, CO2 , nitric oxide, and other small solutes. Ion channel activity has been demonstrated for mammalian AQPs 0, 1, 6, Drosophila Big Brain (BIB), soybean nodulin 26, and rockcress AtPIP2;1. More classes are likely to be discovered. Newly identified blockers are providing essential tools for establishing physiological roles of some of the AQP dual water and ion channels...
April 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29163220/evaluation-of-optogenetic-electrophysiology-tools-in-human-stem-cell-derived-cardiomyocytes
#11
Susann Björk, Elina A Ojala, Tommy Nordström, Antti Ahola, Mikko Liljeström, Jari Hyttinen, Esko Kankuri, Eero Mervaala
Current cardiac drug safety assessments focus on hERG channel block and QT prolongation for evaluating arrhythmic risks, whereas the optogenetic approach focuses on the action potential (AP) waveform generated by a monolayer of human cardiomyocytes beating synchronously, thus assessing the contribution of several ion channels on the overall drug effect. This novel tool provides arrhythmogenic sensitizing by light-induced pacing in combination with non-invasive, all-optical measurements of cardiomyocyte APs and will improve assessment of drug-induced electrophysiological aberrancies...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29145442/downregulation-of-kcnmb4-expression-and-changes-in-bk-channel-subtype-in-hippocampal-granule-neurons-following-seizure-activity
#12
Luke E Whitmire, Ling Ling, Vladslav Bugay, Chase M Carver, Santosh Timilsina, Hui-Hsiu Chuang, David B Jaffe, Mark S Shapiro, Jose E Cavazos, Robert Brenner
A major challenge is to understand maladaptive changes in ion channels that sets neurons on a course towards epilepsy development. Voltage- and calcium-activated K+ (BK) channels contribute to early spike timing in neurons, and studies indicate that the BK channel plays a pathological role in increasing excitability early after a seizure. Here, we have investigated changes in BK channels and their accessory β4 subunit (KCNMB4) in dentate gyrus (DG) granule neurons of the hippocampus, key neurons that regulate excitability of the hippocampus circuit...
2017: PloS One
https://www.readbyqxmd.com/read/29095093/conservation-and-variability-of-the-pore-lining-helices-in-p-loop-channels
#13
Denis B Tikhonov, Boris S Zhorov
The family of P-loop channels, which play key roles in the cell physiology, is characterized by four membrane re-entering extracellular P-loops that connect eight transmembrane helices of the pore-forming domain. The X-ray and cryo-EM structures of the open- and closed-state channels show conserved state-dependent folding despite the sequences are very diverse. In sodium, calcium, TRPV and two-pore channels, the pore-lining helices contain conserved asparagines and may or may not include π-helix bulges. Comparison of the sequence- and 3D-alignemnts suggests that the asparagines appeared in evolution as insertions that are accommodated in two ways: by π-helix bulges, which preserve most of inter-segment contacts, or by twists of the C-terminal thirds and switch of inter-segment contacts...
November 2, 2017: Channels
https://www.readbyqxmd.com/read/29070491/rhoa-increases-asic1a-plasma-membrane-localization-and-calcium-influx-in-pulmonary-arterial-smooth-muscle-cells-following-chronic-hypoxia
#14
Lindsay M Herbert, Thomas C Resta, Nikki L Jernigan
Increases in pulmonary arterial smooth muscle cell (PASMC) intracellular Ca2+ levels and enhanced RhoA/Rho kinase-dependent Ca2+ sensitization are key determinants of PASMC contraction, migration, and proliferation accompanying the development of hypoxic pulmonary hypertension. We previously showed that acid-sensing ion channel 1a (ASIC1a)-mediated Ca2+ entry in PASMC is an important constituent of the active vasoconstriction, vascular remodeling, and right ventricular hypertrophy associated with hypoxic pulmonary hypertension...
February 1, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29027927/conotoxins-as-tools-to-understand-the-physiological-function-of-voltage-gated-calcium-ca-v-channels
#15
REVIEW
David Ramírez, Wendy Gonzalez, Rafael A Fissore, Ingrid Carvacho
Voltage-gated calcium (CaV ) channels are widely expressed and are essential for the completion of multiple physiological processes. Close regulation of their activity by specific inhibitors and agonists become fundamental to understand their role in cellular homeostasis as well as in human tissues and organs. CaV channels are divided into two groups depending on the membrane potential required to activate them: High-voltage activated (HVA, CaV 1.1-1.4; CaV 2.1-2.3) and Low-voltage activated (LVA, CaV 3.1-3...
October 13, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28810912/inhibition-of-trpm7-suppresses-cell-proliferation-of-colon-adenocarcinoma-in-vitro-and-induces-hypomagnesemia-in-vivo-without-affecting-azoxymethane-induced-early-colon-cancer-in-mice
#16
Junhao Huang, Hideki Furuya, Malika Faouzi, Zheng Zhang, Mahealani Monteilh-Zoller, Kelly Galbraith Kawabata, F David Horgen, Toshihiko Kawamori, Reinhold Penner, Andrea Fleig
BACKGROUND: Magnesium (Mg(2+)) is an essential cation implicated in carcinogenesis, solid tumor progression and metastatic potential. The Transient Receptor Potential Melastatin Member 7 (TRPM7) is a divalent ion channel involved in cellular and systemic Mg(2+) homeostasis. Abnormal expression of TRPM7 is found in numerous cancers, including colon, implicating TRPM7 in this process. METHODS: To establish a possible link between systemic magnesium (Mg(2+)) status, the Mg(2+) conducting channel TRPM7 in colon epithelial cells, and colon carcinogenesis, in vitro whole-cell patch clamp electrophysiology, qPCR, and pharmacological tools were used probing human colorectal adenocarcinoma HT-29 as well as normal primary mouse colon epithelial cells...
August 15, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28759041/oncosis-and-apoptosis-induction-by-activation-of-an-overexpressed-ion-channel-in-breast-cancer-cells
#17
A A Peters, S Y N Jamaludin, K T D S Yapa, S Chalmers, A P Wiegmans, H F Lim, M J G Milevskiy, I Azimi, F M Davis, K S Northwood, E Pera, D L Marcial, E Dray, N J Waterhouse, P J Cabot, T J Gonda, P A Kenny, M A Brown, K K Khanna, S J Roberts-Thomson, G R Monteith
The critical role of calcium signalling in processes related to cancer cell proliferation and invasion has seen a focus on pharmacological inhibition of overexpressed ion channels in specific cancer subtypes as a potential therapeutic approach. However, despite the critical role of calcium in cell death pathways, pharmacological activation of overexpressed ion channels has not been extensively evaluated in breast cancer. Here we define the overexpression of transient receptor potential vanilloid 4 (TRPV4) in a subgroup of breast cancers of the basal molecular subtype...
November 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28728818/mechanosensitive-piezo-channels-in-the-gastrointestinal-tract
#18
REVIEW
C Alcaino, G Farrugia, A Beyder
Sensation of mechanical forces is critical for normal function of the gastrointestinal (GI) tract and abnormalities in mechanosensation are linked to GI pathologies. In the GI tract there are several mechanosensitive cell types-epithelial enterochromaffin cells, intrinsic and extrinsic enteric neurons, smooth muscle cells and interstitial cells of Cajal. These cells use mechanosensitive ion channels that respond to mechanical forces by altering transmembrane ionic currents in a process called mechanoelectrical coupling...
2017: Current Topics in Membranes
https://www.readbyqxmd.com/read/28723646/collagen-type-1-promotes-survival-of-human-breast-cancer-cells-by-overexpressing-kv10-1-potassium-and-orai1-calcium-channels-through-ddr1-dependent-pathway
#19
Mehdi Badaoui, Cloé Mimsy-Julienne, Charles Saby, Laurence Van Gulick, Marta Peretti, Pierre Jeannesson, Hamid Morjani, Halima Ouadid-Ahidouch
Collagen type 1 is among the tumor microenvironment (TM) factors, that regulates proliferation, survival, migration and invasion. Ion channels are key players in interactions between tumor cells and TM. Kv10.1 has been shown to play an essential role in breast cancer cell proliferation and migration by permitting Ca2+ influx notably via Orai1. Here, we show that human breast cancer (BC) cells growing, in culture media completely devoid of the serum and seeded on collagen 1 coating, exhibited less apoptotic rate and a decrease in Bax expression when compared to those grown on plastic...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28693898/nanosecond-pulsed-electric-fields-depolarize-transmembrane-potential-via-voltage-gated-k-ca-2-and-trpm8-channels-in-u87-glioblastoma-cells
#20
Ryan C Burke, Sylvia M Bardet, Lynn Carr, Sergii Romanenko, Delia Arnaud-Cormos, Philippe Leveque, Rodney P O'Connor
Nanosecond pulsed electric fields (nsPEFs) have a variety of applications in the biomedical and biotechnology industries. Cancer treatment has been at the forefront of investigations thus far as nsPEFs permeabilize cellular and intracellular membranes leading to apoptosis and necrosis. nsPEFs may also influence ion channel gating and have the potential to modulate cell physiology without poration of the membrane. This phenomenon was explored using live cell imaging and a sensitive fluorescent probe of transmembrane voltage in the human glioblastoma cell line, U87 MG, known to express a number of voltage-gated ion channels...
October 2017: Biochimica et Biophysica Acta
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