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https://www.readbyqxmd.com/read/27911331/excitation-contraction-coupling-alterations-in-myopathies
#1
Isabelle Marty, Julien Fauré
During the complex series of events leading to muscle contraction, the initial electric signal coming from motor neurons is transformed into an increase in calcium concentration that triggers sliding of myofibrils. This process, referred to as excitation-contraction coupling, is reliant upon the calcium-release complex, which is restricted spatially to a sub-compartment of muscle cells ("the triad") and regulated precisely. Any dysfunction in the calcium-release complex leads to muscle impairment and myopathy...
November 29, 2016: Journal of Neuromuscular Diseases
https://www.readbyqxmd.com/read/27910855/l-type-calcium-channels-regulate-filopodia-stability-and-cancer-cell-invasion-downstream-of-integrin-signalling
#2
Guillaume Jacquemet, Habib Baghirov, Maria Georgiadou, Harri Sihto, Emilia Peuhu, Pierre Cettour-Janet, Tao He, Merja Perälä, Pauliina Kronqvist, Heikki Joensuu, Johanna Ivaska
Mounting in vitro, in vivo and clinical evidence suggest an important role for filopodia in driving cancer cell invasion. Using a high-throughput microscopic-based drug screen, we identify FDA-approved calcium channel blockers (CCBs) as potent inhibitors of filopodia formation in cancer cells. Unexpectedly, we discover that L-type calcium channels are functional and frequently expressed in cancer cells suggesting a previously unappreciated role for these channels during tumorigenesis. We further demonstrate that, at filopodia, L-type calcium channels are activated by integrin inside-out signalling, integrin activation and Src...
December 2, 2016: Nature Communications
https://www.readbyqxmd.com/read/27907088/silver-nanoparticle-directed-mast-cell-degranulation-is-mediated-through-calcium-and-pi3k-signaling-independent-of-the-high-affinity-ige-receptor
#3
Nasser B Alsaleh, Indushekhar Persaud, Jared M Brown
Engineered nanomaterial (ENM)-mediated toxicity often involves triggering immune responses. Mast cells can regulate both innate and adaptive immune responses and are key effectors in allergic diseases and inflammation. Silver nanoparticles (AgNPs) are one of the most prevalent nanomaterials used in consumer products due to their antimicrobial properties. We have previously shown that AgNPs induce mast cell degranulation that was dependent on nanoparticle physicochemical properties. Furthermore, we identified a role for scavenger receptor B1 (SR-B1) in AgNP-mediated mast cell degranulation...
2016: PloS One
https://www.readbyqxmd.com/read/27906696/medical-therapy-refractory-chronic-rhinosinusitis-and-productivity-costs
#4
Kristine A Smith, Luke Rudmik
PURPOSE OF REVIEW: The purpose of this review is to address the most recent advances in the medical therapy for chronic rhinosinusitis (CRS), define recalcitrant and refractory CRS, and discuss the productivity costs associated with CRS. RECENT FINDINGS: Recent studies evaluating anti-IL-4 receptor α antibodies and calcium channel blockers have demonstrated promising early results during management of CRS. Recent appropriateness criteria have been developed to assist clinicians with defining which patients have 'refractory' CRS and may be considered candidates for endoscopic sinus surgery...
November 30, 2016: Current Opinion in Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27906239/fiber-optic-electron-spin-resonance-thermometry-of-single-laser-activated-neurons
#5
A A Lanin, I V Fedotov, Yu G Ermakova, D A Sidorov-Biryukov, A B Fedotov, P Hemmer, V V Belousov, A M Zheltikov
Optically detected electron spin resonance in fiber-coupled nitrogen-vacancy (NV) centers of diamond is used to demonstrate a fiber-optic quantum thermometry of individual thermogenetically activated neurons. Laser-induced temperature variations read out from single neurons with the NV-diamond fiber sensor are shown to strongly correlate with the fluorescence of calcium-ion sensors, serving as online indicators of the inward Ca<sup>2+</sup> current across the cell membrane of neurons expressing transient receptor potential (TRP) cation channels...
December 1, 2016: Optics Letters
https://www.readbyqxmd.com/read/27906063/characterization-of-a-multiprotein-complex-involved-in-excitation-transcription-coupling-of-skeletal-muscle
#6
Manuel Arias-Calderón, Gonzalo Almarza, Alexis Díaz-Vegas, Ariel Contreras-Ferrat, Denisse Valladares, Mariana Casas, Héctor Toledo, Enrique Jaimovich, Sonja Buvinic
BACKGROUND: Electrical activity regulates the expression of skeletal muscle genes by a process known as "excitation-transcription" (E-T) coupling. We have demonstrated that release of adenosine 5'-triphosphate (ATP) during depolarization activates membrane P2X/P2Y receptors, being the fundamental mediators between electrical stimulation, slow intracellular calcium transients, and gene expression. We propose that this signaling pathway would require the proper coordination between the voltage sensor (dihydropyridine receptor, DHPR), pannexin 1 channels (Panx1, ATP release conduit), nucleotide receptors, and other signaling molecules...
April 11, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27905548/neurexin-regulates-nighttime-sleep-by-modulating-synaptic-transmission
#7
Huawei Tong, Qian Li, Zi Chao Zhang, Yi Li, Junhai Han
Neurexins are cell adhesion molecules involved in synaptic formation and synaptic transmission. Mutations in neurexin genes are linked to autism spectrum disorders (ASDs), which are frequently associated with sleep problems. However, the role of neurexin-mediated synaptic transmission in sleep regulation is unclear. Here, we show that lack of the Drosophila α-neurexin homolog significantly reduces the quantity and quality of nighttime sleep and impairs sleep homeostasis. We report that neurexin expression in Drosophila mushroom body (MB) αβ neurons is essential for nighttime sleep...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27905406/differential-roles-for-l-type-calcium-channel-subtypes-in-alcohol-dependence
#8
Stefanie Uhrig, David Vandael, Andrea Marcantoni, Nina Dedic, Ainhoa Bilbao, Miriam A Vogt, Natalie Hirth, Laura Broccoli, Rick E Bernardi, Kai Schönig, Peter Gass, Dusan Bartsch, Rainer Spanagel, Jan M Deussing, Wolfgang H Sommer, Emilio Carbone, Anita C Hansson
It has previously been shown that the inhibition of L-type calcium channels (LTCCs) decreases alcohol consumption, although the contribution of the central LTCC subtypes Cav1.2 and Cav1.3 remains unknown. Here, we determined changes in Cav1.2 (Cacna1c) and Cav1.3 (Cacna1d) mRNA and protein expression in alcohol dependent rats during protracted abstinence and naïve controls using in situ hybridization and Western Blot analysis. Functional validation was obtained by electrophysiological recordings of calcium currents in dissociated hippocampal pyramidal neurons...
December 1, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27904663/t-type-calcium-channel-blocker-attenuates-unilateral-ureteral-obstruction-induced-renal-interstitial-fibrosis-by-activating-the-nrf2-antioxidant-pathway
#9
Sungjin Chung, Soojeong Kim, Minyoung Kim, Eun Sil Koh, Hye Eun Yoon, Ho-Shik Kim, Cheol Whee Park, Yoon Sik Chang, Seok Joon Shin
Besides its effect on high blood pressure, T-type calcium channel blocker is renoprotective in experimental models of renal fibrosis. However, the exact mechanism of T-type calcium channel blocker on tubulointerstitial fibrosis is unclear. We investigated whether the renoprotective effect of T-type calcium channel blocker is associated with modulation of the signaling of oxidative stress-induced renal fibrosis. Treatment with a non-hypotensive dose of efonidipine, a T-type calcium channel blocker, or nifedipine, an L-type channel blocker, was initiated one day before unilateral ureteral obstruction (UUO) in C57BL6/J mice, and was continued until 3 and 7 days after UUO...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27904156/effects-of-calcium-channel-blocker-benidipine-based-combination-therapy-on-target-blood-pressure-control-and-cardiovascular-outcome-a-sub-analysis-of-the-cope-trial
#10
Seiji Umemoto, Toshio Ogihara, Masunori Matsuzaki, Hiromi Rakugi, Yasuo Ohashi, Takao Saruta
We compared three benidipine-based regimens-that is, benidipine plus angiotensin receptor blocker (ARB), β-blocker (BB) or thiazide-and found that the benidipine-BB combination was less beneficial in reducing the risk of stroke than the benidipine-thiazide combination. This sub-analysis sought to compare the effects of reaching a target blood pressure (BP) (<140/90 mm Hg) on the cardiovascular outcomes among the three benidipine-based treatment groups in the Combination Therapy of Hypertension to Prevent Cardiovascular Events trial...
December 1, 2016: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/27903742/p2y6-receptor-antagonist-mrs2578-inhibits-neutrophil-activation-and-aggregated-neutrophil-extracellular-trap-formation-induced-by-gout-associated-monosodium-urate-crystals
#11
Payel Sil, Craig P Hayes, Barbara J Reaves, Patrick Breen, Shannon Quinn, Jeremy Sokolove, Balázs Rada
Human neutrophils (polymorphonuclear leukocytes [PMNs]) generate inflammatory responses within the joints of gout patients upon encountering monosodium urate (MSU) crystals. Neutrophil extracellular traps (NETs) are found abundantly in the synovial fluid of gout patients. The detailed mechanism of MSU crystal-induced NET formation remains unknown. Our goal was to shed light on possible roles of purinergic signaling and neutrophil migration in mediating NET formation induced by MSU crystals. Interaction of human neutrophils with MSU crystals was evaluated by high-throughput live imaging using confocal microscopy...
November 30, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27902567/dorsal-root-ganglion-neurons-become-hyperexcitable-and-increase-expression-of-voltage-gated-t-type-calcium-channels-cav3-2-in-paclitaxel-induced-peripheral-neuropathy
#12
Yan Li, Claudio Esteves Tatsui, Laurence D Rhines, Robert Y North, Daniel S Harrison, Ryan M Cassidy, Caj A Johansson, Alyssa K Kosturakis, Denaya D Edwards, Hongmei Zhang, Patrick M Dougherty
Here it is shown that paclitaxel induced neuropathy is associated with the development of spontaneous activity (SA) and hyperexcitability in DRG neurons that is paralleled by increased expression of low-voltage-activated calcium channels (T-type; Cav3.2). The percentage of DRG neurons showing SA and the overall mean rate of SA were significantly higher at day 7 of paclitaxel treatment than in rats receiving vehicle. Cav3.2 expression was increased in L4-6 DRG and spinal cord segments in paclitaxel-treated rats, localized to small calcitonin gene-related peptide expressing and isolectin B4 expressing DRG neurons and to glial fibrillary acidic protein-positive spinal cord cells...
November 24, 2016: Pain
https://www.readbyqxmd.com/read/27901061/inter-individual-variability-and-modeling-of-electrical-activity-a-possible-new-approach-to-explore-cardiac-safety
#13
Jean-Yves Le Guennec, Jérôme Thireau, Aude Ouillé, Julien Roussel, Jérôme Roy, Serge Richard, Sylvain Richard, Eric Martel, Pascal Champéroux
Safety pharmacology aims to predict rare side effects of new drugs. We explored whether rare pro-arrhythmic effects could be linked to the variability of the effects of these drugs on ion currents and whether taking into consideration this variability in computational models could help to better detect and predict cardiac side effects. For this purpose, we evaluated how intra- and inter-individual variability influences the effect of hERG inhibition on both the action potential duration and the occurrence of arrhythmias...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27900342/cacna1c-protecting-young-hippocampal-neurons-in-the-adult-brain
#14
Héctor De Jesús-Cortés, Anjali M Rajadhyaksha, Andrew A Pieper
Neuropsychiatric disease is the leading cause of disability in the United States, and fourth worldwide.(1,2) Not surprisingly, human genetic studies have revealed a common genetic predisposition for many forms of neuropsychiatric disease, potentially explaining why overlapping symptoms are commonly observed across multiple diagnostic categories. For example, the CACNA1C gene was recently identified in the largest human genome-wide association study to date as a risk loci held in common across 5 major forms of neuropsychiatric disease: bipolar disorder, schizophrenia, major depressive disorder (MDD), autism spectrum disorder and attention deficit-hyperactivity disorder...
2016: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/27899482/transient-receptor-potential-canonical-3-trpc3-channels-are-required-for-hypothalamic-glucose-detection-and-energy-homeostasis
#15
Chloé Chrétien, Claire Fenech, Fabienne Liénard, Sylvie Grall, Charlène Chevalier, Sylvie Chaudy, Xavier Brenachot, Raymond Berges, Katie Louche, Romana Stark, Emmanuelle Nédélec, Amélie Laderrière, Zane B Andrews, Alexandre Benani, Veit Flockerzi, Jean Gascuel, Jana Hartmann, Cédric Moro, Lutz Birnbaumer, Corinne Leloup, Luc Pénicaud, Xavier Fioramonti
The medio-basal hypothalamus (MBH) contains neurons capable of directly detecting metabolic signals such as glucose to control energy homeostasis. Among them, glucose-excited (GE) neurons increase their electrical activity when glucose rises. In view of previous work, we hypothesized that Transient Receptor Potential Canonical type-3 (TRPC3) channels are involved in hypothalamic glucose detection and the control of energy homeostasis.To investigate the role of TRPC3, we used constitutive and conditional TRPC3-deficient mice models...
November 29, 2016: Diabetes
https://www.readbyqxmd.com/read/27899413/calcium-channel-regulator-mid1-links-torc2-mediated-changes-in-mitochondrial-respiration-to-autophagy
#16
Ariadne Vlahakis, Nerea Lopez Muniozguren, Ted Powers
Autophagy is a catabolic process that recycles cytoplasmic contents and is crucial for cell survival during stress. The target of rapamycin (TOR) kinase regulates autophagy as part of two distinct protein complexes, TORC1 and TORC2. TORC1 negatively regulates autophagy according to nitrogen availability. In contrast, TORC2 functions as a positive regulator of autophagy during amino acid starvation, via its target kinase Ypk1, by repressing the activity of the calcium-dependent phosphatase calcineurin and promoting the general amino acid control (GAAC) response...
November 29, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27899270/limitations-in-electrophysiological-model-development-and-validation-caused-by-differences-between-simulations-and-experimental-protocols
#17
REVIEW
Jesús Carro, José F Rodríguez-Matas, Violeta Monasterio, Esther Pueyo
Models of ion channel dynamics are usually built by fitting isolated cell experimental values of individual parameters while neglecting the interaction between them. Another shortcoming regards the estimation of ionic current conductances, which is often based on quantification of Action Potential (AP)-derived markers. Although this procedure reduces the uncertainty in the calculation of conductances, many studies evaluate electrophysiological AP-derived markers from single cell simulations, whereas experimental measurements are obtained from tissue preparations...
November 26, 2016: Progress in Biophysics and Molecular Biology
https://www.readbyqxmd.com/read/27899046/chili-pepper-as-a-body-weight-loss-food
#18
Sharon Varghese, Peter Kubatka, Luis Rodrigo, Katarina Gazdikova, Martin Caprnda, Julia Fedotova, Anthony Zulli, Peter Kruzliak, Dietrich Büsselberg
Chili has culinary as well as medical importance. Studies in humans, using a wide range of doses of chili intake (varying from a single meal to a continuous uptake for up to 12 weeks), concluded that it facilitates weight loss. In regard to this, the main targets of chili are fat metabolism, energy expenditure, and thermogenesis. To induce weight loss, the active substance of chili, capsaicin, activates Transient Receptor Potential Cation Channel sub-family V member 1 (TRPV1) channels) receptors causing an increase in intracellular calcium levels and triggering the sympathetic nervous system...
November 29, 2016: International Journal of Food Sciences and Nutrition
https://www.readbyqxmd.com/read/27898257/assessment-of-nifedipine-therapy-in-hyperinsulinemic-hypoglycemia-due-to-mutations-in-the-abcc8-gene
#19
M Güemes, P Shah, S Silvera, K Morgan, C Gilbert, L Hinchey, K Hussain
CONTEXT: Previous case reports have documented the effectiveness of L-type calcium channel blockers (such as Nifedipine and Verapamil) for treating different forms of hyperinsulinemic hypoglycemia (HH). OBJECTIVE: To systematically assess the glycemic response to Nifedipine therapy in 11 patients with HH due to mutations in the ABCC8 gene. DESIGN: Dose escalation of Nifedipine therapy Setting: Inpatients at a tertiary hospital Patients or Other Participants: 11 children with diazoxide unresponsive HH due to mutations in the ABCC8 gene...
November 29, 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27897119/glaucoma-hot-topics-in-pharmacology
#20
Shiama I Balendra, Parth Arvind Shah, Mishank Jain, Andrzej Grzybowski, Francesca M Cordeiro
BACKGROUND: Glaucoma comprises a group of neurodegenerative diseases resulting in retinal ganglion cell death within the optic nerve head. It is projected to affect almost 80 million people worldwide by 2020. The condition's asymptomatic nature translates to over half of glaucoma sufferers being unaware of their condition. By the time of diagnosis, irreversible blindness is likely to have occurred. Prime areas of glaucoma research therefore include identification and optimization of risk factors for the disease, accurate and early diagnostic tools and novel therapeutic methods...
November 29, 2016: Current Pharmaceutical Design
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