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Ion channels, cell calcium, pharmacology,

Florian Rouaud, Jean-Luc Boucher, Anny Slama-Schwok, Stéphane Rocchi
Melanoma is one of the most lethal cancers when it reaches a metastatic stage. Despite the spectacular achievements of targeted therapies (BRAF inhibitors) or immuno-therapies (anti-CTLA4 or anti-PD1), most patients with melanoma will need additional treatments. Here we used a photoactive NADPH analogue called NS1 to induce cell death by inhibition of NADPH oxidases NOX in melanoma cells, including melanoma cells isolated from patients. In contrast, healthy melanocytes growth was unaffected by NS1 treatment...
October 14, 2016: Oncotarget
Bernhard Stenger, Tanja Popp, Harald John, Markus Siegert, Amelie Tsoutsoulopoulos, Annette Schmidt, Harald Mückter, Thomas Gudermann, Horst Thiermann, Dirk Steinritz
Transient receptor potential family channels (TRPs) have been identified as relevant targets in many pharmacological as well as toxicological studies. TRP channels are ubiquitously expressed in different tissues and act among others as sensors for different external stimuli, such as mechanical stress or noxious impacts. Recent studies suggest that one member of this family, the transient receptor potential ankyrin 1 cation channel (TRPA1), is involved in pain, itch, and various diseases, suggesting TRPA1 as a potential therapeutic target...
October 13, 2016: Archives of Toxicology
Ingrid Carvacho, Goli Ardestani, Hoi Chang Lee, Kaitlyn McGarvey, Rafael A Fissore, Karin Lykke-Hartmann
The Transient Receptor Potential (TRP) channels are a family of cationic ion channels widely distributed in mammalian tissues. In general, the global genetic disruption of individual TRP channels result in phenotypes associated with impairment of a particular tissue and/or organ function. An exception is the genetic ablation of the TRP channel TRPM7, which results in early embryonic lethality. Nevertheless, the function of TRPM7 in oocytes, eggs and pre-implantation embryos remains unknown. Here, we described an outward rectifying non-selective current mediated by a TRP ion channel in immature oocytes (germinal vesicle stage), matured oocytes (metaphase II eggs) and 2-cell stage embryos...
September 29, 2016: Scientific Reports
Stacey Ann N D'mello, Wayne R Joseph, Taryn N Green, Euphemia Y Leung, Matthew J During, Graeme J Finlay, Bruce C Baguley, Maggie L Kalev-Zylinska
GRIN2A mutations are frequent in melanoma tumours but their role in disease is not well understood. GRIN2A encodes a modulatory subunit of the N-methyl-d-aspartate receptor (NMDAR). We hypothesized that certain GRIN2A mutations increase NMDAR function and support melanoma growth through oncogenic effects. This hypothesis was tested using 19 low-passage melanoma cell lines, four of which carried novel missense mutations in GRIN2A that we previously reported. We examined NMDAR expression, function of a calcium ion (Ca(2+)) channel and its contribution to cell growth using pharmacological modulators; findings were correlated with the presence or absence of GRIN2A mutations...
September 14, 2016: Cell Calcium
Hege E Larsen, Emma N Bardsley, Konstantinos Lefkimmiatis, David J Paterson
UNLABELLED: Hypertension is associated with impaired nitric oxide (NO)-cyclic nucleotide (CN)-coupled intracellular calcium (Ca(2+)) homeostasis that enhances cardiac sympathetic neurotransmission. Because neuronal membrane Ca(2+) currents are reduced by NO-activated S-nitrosylation, we tested whether CNs affect membrane channel conductance directly in neurons isolated from the stellate ganglia of spontaneously hypertensive rats (SHRs) and their normotensive controls. Using voltage-clamp and cAMP-protein kinase A (PKA) FRET sensors, we hypothesized that impaired CN regulation provides a direct link to abnormal signaling of neuronal calcium channels in the SHR and that targeting cGMP can restore the channel phenotype...
August 17, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Daniel C Millard, Christopher J Strock, Coby B Carlson, Natsuyo Aoyama, Krisztina Juhasz, Tom A Goetze, Sonja Stoelzle-Feix, Nadine Becker, Niels Fertig, Craig T January, Blake D Anson, James D Ross
Drug-drug interactions pose a difficult drug safety problem, given the increasing number of individuals taking multiple medications and the relative complexity of assessing the potential for interactions. For example, sofosbuvir-based drug treatments have significantly advanced care for hepatitis C virus-infected patients, yet recent reports suggest interactions with amiodarone may cause severe symptomatic bradycardia and thus limit an otherwise extremely effective treatment. Here, we evaluated the ability of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) to recapitulate the interaction between sofosbuvir and amiodarone in vitro, and more generally assessed the feasibility of hiPSC-CMs as a model system for drug-drug interactions...
August 7, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
Meichun Deng, Zhaotun Hu, Tianfu Cai, Kai Liu, Wenfang Wu, Xuan Luo, Liping Jiang, Meichi Wang, Jing Yang, Yucheng Xiao, Songping Liang
Chinese tarantula Ornithoctonus huwena is one of the most venomous spiders distributing in the hilly areas of southern China. In this study, using whole-cell patch-clamp technique we investigated electrophysiological and pharmacological properties of ion channels from tarantula subesophageal ganglion neurons. It was found that the neurons express multiple kinds of ion channels at least including voltage-gated calcium channels, TTX-sensitive sodium channels and two types of potassium channels. They exhibit pharmacological properties similar to mammalian subtypes...
September 15, 2016: Toxicon: Official Journal of the International Society on Toxinology
Fernanda B Morrone, Marina P Gehring, Natália F Nicoletti
Malignant brain tumors are highly lethal and aggressive. Despite recent advances in the current therapies, which include the combination of surgery and radio/chemotherapy, the average survival rate remains poor. Altered regulation of ion channels is part of the neoplastic transformation, which suggests that ion channels are involved in cancer. Distinct classes of calcium-permeable channels are abnormally expressed in cancer and are likely involved in the alterations underlying malignant growth. Specifically, cytosolic Ca(2+) activity plays an important role in the regulation of cell proliferation, and Ca(2+) signaling is altered in proliferating tumor cells...
September 2016: Molecular Pharmacology
Jian Zhang, Xiaoling Li, Herman Kwansa, Yun Tai Kim, Liye Yi, Gina Hong, Shaida A Andrabi, Valina L Dawson, Ted M Dawson, Raymond C Koehler, Zeng-Jin Yang
Tissue acidosis is a key component of cerebral ischemic injury, but its influence on cell death signaling pathways is not well defined. One such pathway is parthanatos, in which oxidative damage to DNA results in activation of poly(ADP-ribose) polymerase and generation of poly(ADP-ribose) polymers that trigger release of mitochondrial apoptosis-inducing factor. In primary neuronal cultures, we first investigated whether acidosis per sé is capable of augmenting parthanatos signaling initiated pharmacologically with the DNA alkylating agent, N-methyl-N'-nitro-N-nitrosoguanidine...
July 5, 2016: Journal of Cerebral Blood Flow and Metabolism
Paul J Buchanan, Karen D McCloskey
The importance of ion channels in the hallmarks of many cancers is increasingly recognised. This article reviews current knowledge of the expression of members of the voltage-gated calcium channel family (CaV) in cancer at the gene and protein level and discusses their potential functional roles. The ten members of the CaV channel family are classified according to expression of their pore-forming α-subunit; moreover, co-expression of accessory α2δ, β and γ confers a spectrum of biophysical characteristics including voltage dependence of activation and inactivation, current amplitude and activation/inactivation kinetics...
June 24, 2016: European Biophysics Journal: EBJ
Samuel Bertin, Yukari Aoki-Nonaka, Jihyung Lee, Petrus R de Jong, Peter Kim, Tiffany Han, Timothy Yu, Keith To, Naoki Takahashi, Brigid S Boland, John T Chang, Samuel B Ho, Scott Herdman, Maripat Corr, Alessandra Franco, Sonia Sharma, Hui Dong, Armen N Akopian, Eyal Raz
OBJECTIVE: Transient receptor potential ankyrin-1 (TRPA1) and transient receptor potential vanilloid-1 (TRPV1) are calcium (Ca(2+))-permeable ion channels mostly known as pain receptors in sensory neurons. However, growing evidence suggests their crucial involvement in the pathogenesis of IBD. We explored the possible contribution of TRPA1 and TRPV1 to T-cell-mediated colitis. DESIGN: We evaluated the role of Trpa1 gene deletion in two models of experimental colitis (ie, interleukin-10 knockout and T-cell-adoptive transfer models)...
June 20, 2016: Gut
Aniello Schiano Moriello, Luciano De Petrocellis
The transient receptor potential vanilloid-1 ion channel (TRPV1) is a non-selective ligand-gated cation channel. It is an integrator of a wide variety of exogenous and endogenous physical and chemical stimuli, including capsaicin, noxious heat (>42 °C), and protons (pH < 5.2). TRPV1 is expressed predominantly in primary sensory neurons involved in pain sensation, but also in other neuronal cell types, in the plasma membrane of different non-neuronal cells such as immune cells, keratinocytes, smooth muscle cells, and in the urothelium...
2016: Methods in Molecular Biology
Ingra Mannhardt, Kaja Breckwoldt, David Letuffe-Brenière, Sebastian Schaaf, Herbert Schulz, Christiane Neuber, Anika Benzin, Tessa Werner, Alexandra Eder, Thomas Schulze, Birgit Klampe, Torsten Christ, Marc N Hirt, Norbert Huebner, Alessandra Moretti, Thomas Eschenhagen, Arne Hansen
Analyzing contractile force, the most important and best understood function of cardiomyocytes in vivo is not established in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). This study describes the generation of 3D, strip-format, force-generating engineered heart tissues (EHT) from hiPSC-CM and their physiological and pharmacological properties. CM were differentiated from hiPSC by a growth factor-based three-stage protocol. EHTs were generated and analyzed histologically and functionally...
July 12, 2016: Stem Cell Reports
Laura V Gonzalez Bosc, Danielle R Plomaritas, Lindsay M Herbert, Wieslawa Giermakowska, Carly Browning, Nikki L Jernigan
The development of chronic hypoxia (CH)-induced pulmonary hypertension is associated with increased pulmonary arterial smooth muscle cell (PASMC) Ca(2+) influx through acid-sensing ion channel-1 (ASIC1) and activation of the Ca(2+)/calcineurin-dependent transcription factor known as nuclear factor of activated T-cells isoform c3 (NFATc3). Whether Ca(2+) influx through ASIC1 contributes to NFATc3 activation in the pulmonary vasculature is unknown. Furthermore, both ASIC1 and calcineurin have been shown to interact with the scaffolding protein known as protein interacting with C kinase-1 (PICK1)...
July 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Jingjia Han, Qingling Wu, Younan Xia, Mary B Wagner, Chunhui Xu
Enhancing the maturation of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) will facilitate their applications in disease modeling and drug discovery. Previous studies suggest that cell alignment could enhance hPSC-CM maturation; however, the robustness of this approach has not been well investigated. To this end, we examined if the anisotropic orientation of hPSC-CMs imposed by the underlying aligned fibers within a 3D microenvironment could improve the maturation of hPSC-CMs. Enriched hPSC-CMs were cultured for two weeks on Matrigel-coated anisotropic (aligned) and isotropic (random) polycaprolactone (PCL) fibrous scaffolds, as well as tissue culture polystyrenes (TCPs) as a control...
May 2016: Stem Cell Research
Luiz H C Vasconcelos, Iara L L Souza, Lílian S Pinheiro, Bagnólia A Silva
Obesity is a multifactorial disease related to metabolic disorders and associated with genetic determinants. Currently, ion channels activity has been linked to many of these disorders, in addition to the central regulation of food intake, energetic balance, hormone release and response, as well as the adipocyte cell proliferation. Therefore, the objective of this work is to review the current knowledge about the influence of ion channels in obesity development. This review used different sources of literature (Google Scholar, PubMed, Scopus, and Web of Science) to assess the role of ion channels in the pathophysiology of obesity...
2016: Frontiers in Pharmacology
E Pueyo, C E Dangerfield, O J Britton, L Virág, K Kistamás, N Szentandrássy, N Jost, A Varró, P P Nánási, K Burrage, B Rodríguez
Beat-to-beat variability in repolarization (BVR) has been proposed as an arrhythmic risk marker for disease and pharmacological action. The mechanisms are unclear but BVR is thought to be a cell level manifestation of ion channel stochasticity, modulated by cell-to-cell differences in ionic conductances. In this study, we describe the construction of an experimentally-calibrated set of stochastic cardiac cell models that captures both BVR and cell-to-cell differences in BVR displayed in isolated canine action potential measurements using pharmacological agents...
2016: PloS One
Tünde Molnár, Oleg Yarishkin, Anthony Iuso, Peter Barabas, Bryan Jones, Robert E Marc, Tam T T Phuong, David Križaj
UNLABELLED: The endoplasmic reticulum (ER) is at the epicenter of astrocyte Ca(2+) signaling. We sought to identify the molecular mechanism underlying store-operated calcium entry that replenishes ER stores in mouse Müller cells. Store depletion, induced through blockade of sequestration transporters in Ca(2+)-free saline, induced synergistic activation of canonical transient receptor potential 1 (TRPC1) and Orai channels. Store-operated TRPC1 channels were identified by their electrophysiological properties, pharmacological blockers, and ablation of the Trpc1 gene...
March 16, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Jun Ni, Zhiming Yu, Guankui Du, Yanyan Zhang, Jemma L Taylor, Chenjia Shen, Jing Xu, Xunyan Liu, Yifeng Wang, Yunrong Wu
BACKGROUND: Tremendous progress has been made in understanding the functions of the GLUTAMATE RECEPTOR-LIKE (GLR) family in Arabidopsis. Still, the functions of OsGLRs in rice, especially the ion channel activities, are largely unknown. RESULTS: Using the aequorin-based luminescence imaging system, we screened the specificity of amino acids involved in the induction of Ca(2+) flux in rice roots. Of all the amino acids tested, glutamate (Glu) was the only one to trigger Ca(2+) flux significantly in rice roots...
December 2016: Rice
Susumu Ohya
Potassium ion (K(+)) channels play an important role in the modulation of calcium ion (Ca(2+)) signaling via control of the membrane potential. In T-lymphocytes, the voltage-gated K(+) channel, KV1.3, and the intermediate-conductance Ca(2+)-activated K(+) channel, KCa3.1, predominantly contribute to K(+) conductance, and are responsible for cell proliferation, differentiation, apoptosis and infiltration. Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, afflicts more than 0...
2016: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
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