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https://www.readbyqxmd.com/read/28650487/engineering-thiophene-based-nanoparticles-to-induce-phototransduction-in-live-cells-under-illumination
#1
M Zangoli, F Di Maria, E Zucchetti, C Bossio, M R Antognazza, G Lanzani, R Mazzaro, F Corticelli, M Baroncini, G Barbarella
We report that nanoparticles prepared from appropriately functionalized polythiophenes once administered to live cells can acquire phototransduction properties under illumination, becoming photoactive sites able to absorb visible light and convert it to an electrical signal through cell membrane polarization. Amine-reactive fluorescent nanoparticles with pendant N-succinimidyl-ester groups (NPs-NHS) are prepared from polythiophenes alternating unsubstituted and 3-(2,5-dioxopyrrolidin-1-yl-8-octanoate)-substituted thiophenes by a nanoprecipitation method...
June 26, 2017: Nanoscale
https://www.readbyqxmd.com/read/28648645/functional-interaction-of-the-two-pore-domain-potassium-channel-task-1-and-caveolin-3
#2
Chen Kang, Victor Hernandez, Keli Hu
The two-pore domain potassium channel TASK-1 is strongly expressed in the heart and has been shown to modulate the resting membrane potential and action potential. However, little is known about the regulation of TASK-1 channels. The present study was designed to determine whether TASK-1 is modulated by caveolin-3, a primary structural protein of cardiac caveolae. Functional studies with the whole-cell voltage clamp technique showed that the expression of caveolin-3 decreased recombinant TASK-1 currents significantly in HEK293T cells, and this effect was prevented by co-expressing the dominant negative mutant caveolin-3 P104L...
June 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28648120/long-qt-syndrome-associated-caveolin-3-mutations-differentially-regulate-the-hyperpolarization-activated-cyclic-nucleotide-gated-channel-4
#3
L J Motloch, R Larbig, T Darabi, S Reda, K A Motloch, B Wernly, M Lichtenauer, T Gebing, A Schwaiger, N Zagidullin, M Wolny, U C Hoppe
Background Caveolin-3 (cav-3) mutations are linked to the long-QT syndrome (LQTS) causing distinct clinical symptoms. Hyperpolarization-activated cyclic nucleotide channel 4 (HCN4) underlies the pacemaker current If. It associates with cav-3 and both form a macromolecular complex. Methods To examine the effects of human LQTS-associated cav-3 mutations on HCN4-channel function, HEK293-cells were cotransfected with HCN4 and wild-type (WT) cav-3 or a LQTS-associated cav-3 mutant (T78M, A85T, S141R, or F97C). HCN4 currents were recorded using the whole-cell patch-clamp technique...
June 26, 2017: Physiology International
https://www.readbyqxmd.com/read/28646166/atp-release-during-cell-swelling-activates-a-ca-2-dependent-cl-current-by-autocrine-mechanism-in-mouse-hippocampal-microglia
#4
E Murana, F Pagani, B Basilico, M Sundukova, L Batti, S Di Angelantonio, B Cortese, A Grimaldi, A Francioso, P Heppenstall, P Bregestovski, C Limatola, D Ragozzino
Microglia cells, resident immune cells of the brain, survey brain parenchyma by dynamically extending and retracting their processes. Cl(-) channels, activated in the cellular response to stretch/swelling, take part in several functions deeply connected with microglia physiology, including cell shape changes, proliferation, differentiation and migration. However, the molecular identity and functional properties of these Cl(-) channels are largely unknown. We investigated the properties of swelling-activated currents in microglial from acute hippocampal slices of Cx3cr1 (+/GFP) mice by whole-cell patch-clamp and imaging techniques...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646025/remodeling-of-repolarization-and-arrhythmia-susceptibility-in-a-myosin-binding-protein-c-knockout-mouse-model
#5
Amir Toib, Chen Zhang, Giulia Borghetti, Xiaoxiao Zhang, Markus Wallner, Yijun Yang, Constantine Troupes, Hajime Kubo, Thomas Sharp, Eric Feldsott, Remus M Berretta, Neil Zalavadia, Danielle Trappanese, Shavonn Harper, Polina Gross, Xiongwen Chen, Sadia Mohsin, Steven Houser
Hypertrophic cardiomyopathy (HCM) is one of the most common genetic cardiac diseases and amongst the leading causes of sudden cardiac death (SCD) in the young. The cellular mechanisms leading to SCD in HCM are not well known. Prolongation of the action potential duration (APD) is a common feature predisposing hypertrophied hearts to SCD. Previous studies have explored the roles of inward Na(+) and Ca(2+) in the development of HCM, but the role of repolarizing K(+) currents have not been defined. The objective of this study was to characterize the arrhythmogenic phenotype and cellular electrophysiological properties of mice with HCM, induced by Myosin Binding Protein C (MyBPC) Knockout (KO) and to test the hypothesis that remodeling of repolarizing K(+) currents cause APD prolongation in MyBPC KO myocytes...
June 23, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28644055/regulation-of-transient-receptor-potential-melastatin-4-channel-by-sarcoplasmic-reticulum-inositol-triphosphate-receptors-role-in-human-detrusor-smooth-muscle-function
#6
Aaron Provence, Eric S Rovner, Georgi V Petkov
We recently reported key physiological roles for Ca(2+)-activated transient receptor potential melastatin 4 (TRPM4) channels in detrusor smooth muscle (DSM). However, the Ca(2+)-signaling mechanisms governing TRPM4 channel activity in human DSM cells are unexplored. As the TRPM4 channels are activated by Ca(2+), inositol 1,4,5-trisphosphate receptor (IP3R)-mediated Ca(2+) release from the sarcoplasmic reticulum represents a potential Ca(2+) source for TRPM4 channel activation. We used clinically-characterized human DSM tissues to investigate the molecular and functional interactions of the IP3Rs and TRPM4 channels...
June 23, 2017: Channels
https://www.readbyqxmd.com/read/28641963/modulation-of-the-heart-s-electrical-properties-by-the-anticonvulsant-drug-retigabine
#7
Lena Rubi, Michael Kovar, Eva Zebedin-Brandl, Xaver Koenig, Manuel Dominguez-Rodriguez, Hannes Todt, Helmut Kubista, Stefan Boehm, Karlheinz Hilber
Retigabine, currently used as antiepileptic drug, has a wide range of potential medical uses. Administration of the drug in patients can lead to QT interval prolongation in the electrocardiogram and to cardiac arrhythmias in rare cases. This suggests that the drug may perturb the electrical properties of the heart, and the underlying mechanisms were investigated here. Effects of retigabine on currents through human cardiac ion channels, heterologously expressed in tsA-201 cells, were studied in whole-cell patch-clamp experiments...
June 19, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28640864/targeting-breast-cancer-cells-by-mrs1477-a-positive-allosteric-modulator-of-trpv1-channels
#8
Mustafa Nazıroğlu, Bilal Çiğ, Walter Blum, Csaba Vizler, Andrea Buhala, Annamária Marton, Róbert Katona, Katalin Jósvay, Beat Schwaller, Zoltán Oláh, László Pecze
There is convincing epidemiological and experimental evidence that capsaicin, a potent natural transient receptor potential cation channel vanilloid member 1 (TRPV1) agonist, has anticancer activity. However, capsaicin cannot be given systemically in large doses, because of its induction of acute pain and neurological inflammation. MRS1477, a dihydropyridine derivative acts as a positive allosteric modulator of TRPV1, if added together with capsaicin, but is ineffective, if given alone. Addition of MRS1477 evoked Ca2+ signals in MCF7 breast cancer cells, but not in primary breast epithelial cells...
2017: PloS One
https://www.readbyqxmd.com/read/28639215/regulation-of-t-type-ca-2-channel-expression-by-herpes-simplex-virus-1-infection-in-sensory-like-nd7-cells
#9
Qiaojuan Zhang, Shao-Chung Hsia, Miguel Martin-Caraballo
Infection of sensory neurons by herpes simplex virus (HSV)-1 disrupts electrical excitability, altering pain sensory transmission. Because of their low threshold for activation, functional expression of T-type Ca(2+) channels regulates various cell functions, including neuronal excitability and neuronal communication. In this study, we have tested the effect of HSV-1 infection on the functional expression of T-type Ca(2+) channels in differentiated ND7-23 sensory-like neurons. Voltage-gated Ca(2+) currents were measured using whole cell patch clamp recordings in differentiated ND7-23 neurons under various culture conditions...
June 21, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28637815/the-pro-inflammatory-cytokine-tumor-necrosis-factor-alpha-excites-subfornical-organ-neurons
#10
Nick James Simpson, Alastair V Ferguson
Tumor necrosis factor alpha (TNFα) is a pro-inflammatory cytokine implicated in cardiovascular and autonomic regulation via actions in the central nervous system. TNFα(-/-) mice do not develop angiotensin II (ANG II)-induced hypertension, and administration of TNFα into the bloodstream of rats increases blood pressure and sympathetic tone. Recent studies have shown that lesion of the subfornical organ (SFO) attenuates the hypertensive and autonomic effects of TNFα, while direct administration of TNFα into the SFO increases blood pressure, suggesting the SFO to be a key site for the actions of TNFα...
June 21, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28637782/the-brugada-syndrome-susceptibility-gene-hey2-modulates-cardiac-transmural-ion-channel-patterning-and-electrical-heterogeneity
#11
Christiaan C Veerman, Svitlana Podliesna, Rafik Tadros, Elisabeth M Lodder, Isabella Mengarelli, Berend de Jonge, Leander Beekman, Julien Barc, Ronald Wilders, Arthur A Wilde, Bastiaan J Boukens, Ruben Coronel, Arie Verkerk, Carol Ann Remme, Connie R Bezzina
Rationale: Genome-wide association studies previously identified an association of rs9388451 at chromosome 6q22.3 (near HEY2) with Brugada syndrome (BrS). The causal gene and underlying mechanism remain unresolved. Objective: We used an integrative approach entailing transcriptomic studies in human hearts and electrophysiological studies in Hey2 heterozygous knockout mice (Hey2(+/-) ) to dissect the underpinnings of the 6q22.31 association with BrS. Methods and Results: We queried expression quantitative trait locus (eQTL) data acquired in 190 human left ventricular (LV) samples from the Genotype-Tissue Expression (GTEx) consortium for cis-eQTL effects of rs9388451 which revealed an association between BrS risk allele dosage and HEY2 expression (β=+0...
June 21, 2017: Circulation Research
https://www.readbyqxmd.com/read/28635080/neuroadaptations-of-presynaptic-and-postsynaptic-gabab-receptor-function-in-the-paraventricular-nucleus-in-response-to-chronic-unpredictable-stress
#12
Yonggang Gao, Jing-Jing Zhou, Yun Zhu, Li Wang, Therese A Kosten, Xiangjian Zhang, De-Pei Li
BACKGROUND: Chronic stress induces an impaired GABAA (γ-aminobutyric acid type A) receptor-mediated inhibition in the hypothalamic paraventricular nucleus (PVN). It is not clear whether GABAB receptor function is altered in chronic stress. We hypothesize that chronic stress alters GABAB receptor function in PVN corticotrophin-releasing hormone (CRH) neurons to control hypothalamus-pituitary-adrenal (HPA) axis activity. EXPERIMENTAL APPROACH: Whole cell patch-clamp recording was performed on PVN-CRH neurons expressing eGFP driven by CRH promoter in brain slices from unstressed rats and rats that had been subjected to chronic unpredictable mild stress (CUMS)...
June 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28634442/mild-traumatic-brain-injury-evokes-pyramidal-neuron-axon-initial-segment-plasticity-and-diffuse-presynaptic-inhibitory-terminal-loss
#13
Michal Vascak, Jianli Sun, Matthew Baer, Kimberle M Jacobs, John T Povlishock
The axon initial segment (AIS) is the site of action potential (AP) initiation, thus a crucial regulator of neuronal activity. In excitatory pyramidal neurons, the high density of voltage-gated sodium channels (NaV1.6) at the distal AIS regulates AP initiation. A surrogate AIS marker, ankyrin-G (ankG) is a structural protein regulating neuronal functional via clustering voltage-gated ion channels. In neuronal circuits, changes in presynaptic input can alter postsynaptic output via AIS structural-functional plasticity...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28633152/state-of-pelvic-and-acetabular-surgery-in-the-developing-world-a-global-survey-of-orthopaedic-surgeons-at-surgical-implant-generation-network-sign-hospitals
#14
Paul S Whiting, Duane R Anderson, Daniel D Galat, Lewis G Zirkle, Douglas W Lundy, Hassan R Mir
OBJECTIVES: To document the current state of pelvic and acetabular surgery in the developing world and to identify critical areas for improvement in the treatment of these complex injuries. DESIGN: A 50-question online survey. SETTING: International, multicenter. PATIENTS/PARTICIPANTS: One hundred eighty-one orthopaedic surgeons at Surgical Implant Generation Network (SIGN) hospitals, which represent a cross-section of institutions in low- and middle-income countries that treat high-energy musculoskeletal trauma...
July 2017: Journal of Orthopaedic Trauma
https://www.readbyqxmd.com/read/28631948/possible-contribution-of-pannexin-1-to-capsaicin-induced-atp-release-in-rat-nasal-columnar-epithelial-cells
#15
Toyoaki Ohbuchi, Ba Hung Do, Hiroki Koizumi, Shoko Takeuchi, Yoichi Ueta, Hideaki Suzuki
Current evidence indicates that transient receptor potential (TRP) channel activity involves a relationship between opening of pannexin-1 and release of ATP into the extracellular space. We examined the effects of agonists of thermosensitive TRP channels (TRPM8, TRPA1, TRPV1, and TRPV2) on ATP release from rat nasal mucosa, and measured ciliary beat frequency (CBF) using digital high-speed video imaging. Single-cell patch clamping from dissociated rat nasal columnar epithelial cells was performed to confirm the relationship between pannexin-1 and TRP...
February 10, 2017: Channels
https://www.readbyqxmd.com/read/28631579/opening-of-katp-channel-regulates-tonic-currents-from-pyramidal-neurons-in-rat-brain
#16
Zhongxia Li, Jiangping Wang, Huimin Yu, Kewen Jiang
BACKGROUND: ATP-sensitive K+ (KATP) channels couple metabolic state to cellular excitability. Activation of neuronal and astrocytic mitochondrial KATP (mitoKATP) channels regulates a variety of neuronal functions. However, less is known about the impact of mitoKATP on tonic γ-aminobutyric acid (GABA) inhibition. Tonic GABA inhibition is mediated by the binding of ambient GABA on extrasynaptic GABA A-type receptors (GABAARs) and is involved in regulating neuronal excitability. METHODS: We determined the impact of activation of KATP channels with diazoxide (DIZ) on tonic inhibition and recorded tonic current from rat cortical layer 5 pyramidal cells by patch-clamp recordings...
June 20, 2017: Canadian Journal of Neurological Sciences. le Journal Canadien des Sciences Neurologiques
https://www.readbyqxmd.com/read/28630041/dysregulated-zn-2-homeostasis-impairs-cardiac-type-2-ryanodine-receptor-and-mitsugumin-23-functions-leading-to-sarcoplasmic-reticulum-ca-2-leakage
#17
Benedict Reilly-O'Donnell, Gavin B Robertson, Angela Karumbi, Connor McIntyre, Wojciech Bal, Miyuki Nishi, Hiroshi Takeshima, Alan J Stewart, Samantha J Pitt
Aberrant Zn2+-homeostasis is associated with dysregulated intracellular Ca2+ release resulting in chronic heart failure. In the failing heart, a small population of cardiac ryanodine receptors (RyR2) display sub-conductance state gating leading to Ca2+ leakage from sarcoplasmic reticulum (SR) stores, which impairs cardiac contractility. Previous evidence suggests contribution of RyR2-independent Ca2+ leakage through an uncharacterized mechanism. We sought to examine the role of Zn2+ in shaping intracellular Ca2+ release in cardiac muscle...
June 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28628890/interleukin-6-induced-activation-of-a-non-selective-outward-cation-conductance-in-human-cardiac-fibroblasts
#18
Vadim Mitrokhin, Viktor Kazanski, Vladimir Kalsin, Mitko Mladenov, Andre Kamkin
BACKGROUND: It has been demonstrated that cardiac fibroblasts of the human heart have several myocyte-like features, induced by inflammation. OBJECTIVES: This study analyzed the changes of the expressed currents in the basal condition and in the presence of interleukin-6 in cultured human cardiac fibroblasts. METHODS: Human cardiac fibroblasts were cultured as monolayers from earlier passages (2-4). Whole-cell voltage clamp experiments were performed on single culture human cardiac fibroblasts...
June 16, 2017: Cytokine
https://www.readbyqxmd.com/read/28626074/a-type-potassium-channels-contribute-to-prorenin-increase-of-firing-activity-in-hypothalamic-vasopressin-neurosecretory-neurons
#19
Soledad Pitra, Javier E Stern
Recent studies support an important contribution of prorenin (PR) and its receptor (PRR) to the regulation of hypothalamic sympathetic and neurosecretory outflows to the cardiovascular system, including systemic release of vasopressin (VP), both under physiological and cardiovascular disease conditions. Still, the identification of precise cellular mechanisms and neuronal/molecular targets remain unknown. We recently showed that PRR is expressed in VP neurons, and that their activation increases neuronal activity...
June 16, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28625719/atypical-dopamine-transporter-inhibitors-r-modafinil-and-jhw-007-differentially-affect-d2-autoreceptor-neurotransmission-and-the-firing-rate-of-midbrain-dopamine-neurons
#20
Alicia J Avelar, J Cao, Amy Hauck Newman, Michael J Beckstead
Abuse of psychostimulants like cocaine that inhibit dopamine (DA) reuptake through the dopamine transporter (DAT) represents a major public health issue, however FDA-approved pharmacotherapies have yet to be developed. Recently a class of ligands termed "atypical DAT inhibitors" has gained attention due to their range of effectiveness in increasing extracellular dopamine (DA) levels without demonstrating significant abuse liability. These compounds not only hold promise as therapeutic agents to treat stimulant use disorders but also as experimental tools to improve our understanding of DAT function...
June 15, 2017: Neuropharmacology
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