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https://www.readbyqxmd.com/read/28432359/role-of-the-ion-channel-extracellular-collar-in-ampa-receptor-gating
#1
Maria V Yelshanskaya, Samaneh Mesbahi-Vasey, Maria G Kurnikova, Alexander I Sobolevsky
AMPA subtype ionotropic glutamate receptors mediate fast excitatory neurotransmission and are implicated in numerous neurological diseases. Ionic currents through AMPA receptor channels can be allosterically regulated via different sites on the receptor protein. We used site-directed mutagenesis and patch-clamp recordings to probe the ion channel extracellular collar, the binding region for noncompetitive allosteric inhibitors. We found position and substitution-dependent effects for introduced mutations at this region on AMPA receptor gating...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28430892/anti-arrhythmic-potential-of-the-late-sodium-current-inhibitor-gs-458967-in-murine-scn5a-1798insd-and-human-scn5a-1795insd-ipsc-derived-cardiomyocytes
#2
Vincent Portero, Simona Casini, Maaike Hoekstra, Arie O Verkerk, Isabella Mengarelli, Luiz Belardinelli, Sridharan Rajamani, Arthur A M Wilde, Connie R Bezzina, Marieke W Veldkamp, Carol Ann Remme
AIM: Selective inhibition of cardiac late sodium current (INaL) is an emerging target in the treatment of ventricular arrhythmias. We investigated the electrophysiological effects of GS-458967 (GS967), a potent, selective inhibitor of INaL, in an overlap syndrome model of both gain and loss of sodium channel function, comprising cardiomyocytes derived from both human SCN5A-1795insD+/- induced pluripotent stem cells (hiPSC-CMs) and mice carrying the homologous mutation Scn5a-1798insD+/-...
April 18, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28428560/combination-of-high-density-microelectrode-array-and-patch-clamp-recordings-to-enable-studies-of-multisynaptic-integration
#3
David Jäckel, Douglas J Bakkum, Thomas L Russell, Jan Müller, Milos Radivojevic, Urs Frey, Felix Franke, Andreas Hierlemann
We present a novel, all-electric approach to record and to precisely control the activity of tens of individual presynaptic neurons. The method allows for parallel mapping of the efficacy of multiple synapses and of the resulting dynamics of postsynaptic neurons in a cortical culture. For the measurements, we combine an extracellular high-density microelectrode array, featuring 11'000 electrodes for extracellular recording and stimulation, with intracellular patch-clamp recording. We are able to identify the contributions of individual presynaptic neurons - including inhibitory and excitatory synaptic inputs - to postsynaptic potentials, which enables us to study dendritic integration...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28427956/curcumin-poly-2-methyl-2-oxazoline-b-tetrahydrofuran-b-2-methyl-2-oxazoline-formulation-an-improved-penetration-and-biological-effect-of-curcumin-in-f508del-cftr-cell-lines
#4
Cristine Gonçalves, Jean-Pierre Gomez, William Même, Bazoly Rasolonjatovo, David Gosset, Steven Nedellec, Philippe Hulin, Cécile Huin, Tony Le Gall, Tristan Montier, Pierre Lehn, Chantal Pichon, Philippe Guégan, Hervé Cheradame, Patrick Midoux
Neutral amphiphilic triblock ABA copolymers are of great interest to solubilize hydrophobic drugs. We reported that a triblock ABA copolymer consisting of methyl-2-oxazoline (MeOx) and tetrahydrofuran (THF) (MeOx6-THF19-MeOx6) (TBCP2) can solubilize curcumin (Cur) a very hydrophobic molecule exhibiting multiple therapeutic effects but whose insolubility and low stability in water is a major drawback for clinical applications. Here, we provide evidences by flow cytometry and confocal microscopy that Cur penetration in normal and ΔF508-CFTR human airway epithelial cell lines is facilitated by TBCP2...
April 17, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28427417/novel-trigenic-cacna1c-des-mypn-mutations-in-a-family-of-hypertrophic-cardiomyopathy-with-early-repolarization-and-short-qt-syndrome
#5
Yanhong Chen, Hector Barajas-Martinez, Dongxiao Zhu, Xihui Wang, Chonghao Chen, Ruijuan Zhuang, Jingjing Shi, Xueming Wu, Yijia Tao, Weidong Jin, Xiaoyan Wang, Dan Hu
BACKGROUND: Hypertrophic cardiomyopathy (HCM) patients with early repolarization (ER) pattern are at higher risk of ventricular arrhythmia, yet the genetic background of this situation has not been well investigated. Here we report novel trigenic mutations detected in a Chinese family of obstructive HCM with ER and short QT syndrome (SQTS). METHODS: Proband and family members underwent detailed medical assessments. DNAs were extracted from peripheral blood leukocytes for genetic screening with next generation method...
April 20, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28419410/selective-and-state-dependent-activation-of-tresk-background-potassium-channel-by-cloxyquin
#6
Miklós Lengyel, Alice Dobolyi, Gábor Czirják, Péter Enyedi
BACKGROUND AND PURPOSE: Cloxyquin (5-cloroquinolin-8-ol) has been previously described as an activator of TRESK (K2P 18.1, TWIK-related spinal cord K(+) channel) background potassium channel. We have examined the specificity of the drug by testing several K2P channels. We have investigated the mechanism of cloxyquin-mediated TRESK activation, focusing on the differences between the physiologically relevant regulatory states of the channel. EXPERIMENTAL APPROACH: Potassium currents were measured by two-electrode voltage clamp in Xenopus oocytes and by whole-cell patch clamp in mouse dorsal root ganglion (DRG) neurons...
April 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28417339/expression-and-function-of-the-small-conductance-ca-2-activated-k-channel-is-decreased-in-urinary-bladder-smooth-muscle-cells-from-female-guinea-pig-with-partial-bladder-outlet-obstruction
#7
Ning Li, Honglin Ding, Xiaoning He, Zizheng Li, Yili Liu
PURPOSE: Overactive bladder (OAB), usually accompanied by partial bladder outlet obstruction (PBOO), is associated with detrusor overactivity (DO) which is related to the increased urinary bladder smooth muscle (UBSM) cells excitability. Small-conductance Ca(2+)-activated K(+) (SK) channels play a constitutive regulatory role of UBSM excitability and contractility. PBOO is associated with the decreased SK channels mRNA expression and the attenuated regulative effect of SK channels on UBSM contractility...
April 17, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28416816/scalable-electrophysiology-in-intact-small-animals-with-nanoscale-suspended-electrode-arrays
#8
Daniel L Gonzales, Krishna N Badhiwala, Daniel G Vercosa, Benjamin W Avants, Zheng Liu, Weiwei Zhong, Jacob T Robinson
Electrical measurements from large populations of animals would help reveal fundamental properties of the nervous system and neurological diseases. Small invertebrates are ideal for these large-scale studies; however, patch-clamp electrophysiology in microscopic animals typically requires invasive dissections and is low-throughput. To overcome these limitations, we present nano-SPEARs: suspended electrodes integrated into a scalable microfluidic device. Using this technology, we have made the first extracellular recordings of body-wall muscle electrophysiology inside an intact roundworm, Caenorhabditis elegans...
April 17, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28416809/perisomatic-changes-in-h-channels-regulate-depressive-behaviors-following-chronic-unpredictable-stress
#9
C S Kim, D H Brager, D Johnston
Chronic stress can be a precipitating factor in the onset of depression. Lentiviral-mediated knockdown of HCN1 protein expression and reduction of functional Ih produce antidepressant behavior. However, whether h-channels are altered in an animal model of depression is not known. We found that perisomatic HCN1 protein expression and Ih-sensitive physiological measurements were significantly increased in dorsal but not in ventral CA1 region/neurons following chronic unpredictable stress (CUS), a widely accepted model for major depressive disorder...
April 18, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28416807/a-simplified-protocol-for-differentiation-of-electrophysiologically-mature-neuronal-networks-from-human-induced-pluripotent-stem-cells
#10
N Gunhanlar, G Shpak, M van der Kroeg, L A Gouty-Colomer, S T Munshi, B Lendemeijer, M Ghazvini, C Dupont, W J G Hoogendijk, J Gribnau, F M S de Vrij, S A Kushner
Progress in elucidating the molecular and cellular pathophysiology of neuropsychiatric disorders has been hindered by the limited availability of living human brain tissue. The emergence of induced pluripotent stem cells (iPSCs) has offered a unique alternative strategy using patient-derived functional neuronal networks. However, methods for reliably generating iPSC-derived neurons with mature electrophysiological characteristics have been difficult to develop. Here, we report a simplified differentiation protocol that yields electrophysiologically mature iPSC-derived cortical lineage neuronal networks without the need for astrocyte co-culture or specialized media...
April 18, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28415676/nitrobenzylthioinosine-mimics-adenosine-to-attenuate-the-epileptiform-discharge-of-hippocampal-neurons-from-epileptic-rats
#11
Hao Huang, Jing Wang, Jun Zhang, Zhong Luo, Dongxu Li, Xiaowei Qiu, Yan Peng, Zhongxiang Xu, Ping Xu, Zucai Xu
Nitrobenzylthioinosine (NBTI), a specific inhibitor of type 1 equilibrative nucleoside transporter, could regulate the extracellular adenosine concentration and have protective roles in seizures. However, the protection mechanism of NBTI in seizures remains poorly understood. Here, the expression pattern and subcellular distribution of adenosine A1 receptor were detected by Western blot analysis and double-labeling immunofluorescence staining in Lithium Chloride-Pilocarpine induced epileptic rat model. At 24 h after pilocarpine induced rat seizures, hippocampal slices were prepared and the evoked excitatory postsynaptic currents (eEPSCs) amplitude of pyramidal neurons in hippocampus CA1 region was recorded using whole-cell patch clamp...
March 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414903/nanopore-logic-operation-with-dna-to-rna-transcription-in-a-droplet-system
#12
Masayuki Ohara, Masahiro Takanoue, Ryuji Kawano
This paper describes an AND logic operation with amplification and transcription from DNA to RNA using T7 RNA polymerase. All four operations, (0 0) to (1 1), with an enzyme reaction can be performed simultaneously using four-droplet devices that are directly connected to a patch-clamp amplifier. The output RNA molecule is detected using a biological nanopore at the single-molecule level. Channel current recordings can be obtained using the enzyme solution. The integration of DNA logic gates into electrochemical devices is necessary to obtain output information in a human-recognizable form...
April 17, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28411554/emodin-suppresses-the-nasopharyngeal-carcinoma-cells-by-targeting-the-chloride-channels
#13
Lianshun Ma, Yaping Yang, Zizhang Yin, Mei Liu, Liwei Wang, Lixin Chen, Linyan Zhu, Haifeng Yang
Emodin is a natural anthraquinone derivative isolated from the Rheum palmatum. Recent studies demonstrated that emodin has anti-cancer activity in different kinds of human cancer cell lines. However, the underlying mechanism has not been very well studied. Our previous studies showed chloride channels is an important target of anti-cancer drugs. Therefore, the purpose of this research was aimed to explore the role of chloride channels involving in the anti-cancer activity of emodin. The proliferation, cell cycle arrest and apoptosis of poorly differentiated human nasopharyngeal carcinoma cells (CNE-2Z) and normal nasopharyngeal epithelial cells (NP69-SV40T) were detected by 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide(MTT)and flow cytometry...
April 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28411183/membrane-permeation-of-arginine-rich-cell-penetrating-peptides-independent-of-transmembrane-potential-as-a-function-of-lipid-composition-and-membrane-fluidity
#14
Rike Wallbrecher, Tobias Ackels, R Alis Olea, Marco J Klein, Lucie Caillon, Jürgen Schiller, Petra H Bovée-Geurts, Toin H van Kuppevelt, Anne S Ulrich, Marc Spehr, Merel J W Adjobo-Hermans, Roland Brock
Cell-penetrating peptides (CPPs) are prominent delivery vehicles to confer cellular entry of (bio-) macromolecules. Internalization efficiency and uptake mechanism depend, next to the type of CPP and cargo, also on cell type. Direct penetration of the plasma membrane is the preferred route of entry as this circumvents endolysosomal sequestration. However, the molecular parameters underlying this import mechanism are still poorly defined. Here, we make use of the frequently used HeLa and HEK cell lines to address the role of lipid composition and membrane potential...
April 11, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28411158/intrinsic-membrane-properties-and-cholinergic-modulation-of-mouse-basal-forebrain-glutamatergic-neurons-in-vitro
#15
Chun Yang, James T McKenna, Ritchie E Brown
The basal forebrain (BF) controls sleep-wake cycles, attention and reward processing. Compared to cholinergic and GABAergic neurons, BF glutamatergic neurons are less well understood, due to difficulties in identification. Here, we use vesicular glutamate transporter 2 (vGluT2)-tdTomato mice, expressing a red fluorescent protein (tdTomato) in the major group of BF glutamatergic neurons (vGluT2+) to characterize their intrinsic electrical properties and cholinergic modulation. Whole-cell, patch-clamp recordings were made from vGluT2+ neurons in coronal BF slices...
April 12, 2017: Neuroscience
https://www.readbyqxmd.com/read/28409833/dietary-salt-blunts-vasodilation-by-stimulating-epithelial-sodium-channels-in-endothelial-cells-from-salt-sensitive-rats
#16
Zi-Rui Wang, Hui-Bin Liu, Ying-Ying Sun, Qing-Qing Hu, Yu-Xia Li, Wei-Wan Zheng, Chang-Jiang Yu, Xin-Yuan Li, Ming-Ming Wu, Bin-Lin Song, Jian-Jun Mu, Zu-Yi Yuan, Zhi-Ren Zhang, He-Ping Ma
BACKGROUND AND PURPOSE: Our recent studies show that the reduced activity of epithelial sodium channels (ENaC) in endothelial cells accounts for the adaptation of vasculature to salt in Sprague-Dawley (SD) rats. The present study examines a hypothesis that enhanced ENaC activity mediates the loss of vasorelaxation in Dahl salt-sensitive (SS) rats. EXPERIMENTAL APPROACH: We used the cell-attached patch-clamp technique to record ENaC activity in split-open mesenteric arteries...
April 13, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28404730/not-flying-blind-a-comparative-study-of-photoreceptor-function-in-flying-and-non-flying-cockroaches
#17
Roman V Frolov, Atsuko Matsushita, Kentaro Arikawa
Flying is often associated with superior visual performance since good vision is crucial for detection and implementation of rapid visually-guided aerial movements. To understand the evolution of insect visual systems it is therefore important to compare phylogenetically related species with different investments into flight capability. Here, we describe and compare morphological and electrophysiological properties of photoreceptors from the habitually flying green cockroach Panchlora nivea, and the American cockroach Periplaneta americana, which flies only at high ambient temperatures...
April 12, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28404687/selective-calcium-dependent-inhibition-of-atp-gated-p2x3-receptors-by-bisphosphonates-induced-endogenous-atp-analogue-apppi
#18
Yevheniia Ishchenko, Anastasia Shakirzyanova, Raisa Giniatullina, Andrei Skorinkin, Geneviev Bart, Petri Turhanen, Jorma Maatta, Jukka Monkkonen, Rashid Giniatullin
Pain is the most unbearable symptom accompanying primary bone cancers and bone metastases. Bone resorptive disorders are often associated with hypercalcemia contributing to the pathological process. Nitrogen-containing bisphosphonates (NBP) are efficiently used to treat bone-cancers and metastases. NBP, apart from their toxic effect on cancer cells, also provide analgesia via poorly understood mechanisms. We have previously shown, that NBP, by inhibiting the mevalonate pathway, induced the formation of the novel ATP-analogues such as ApppI which can potentially be involved in NBP analgesia...
April 12, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28404629/braf-signaling-principles-unveiled-by-large-scale-human-mutation-analysis-with-a-rapid-lentivirus-based-gene-replacement-method
#19
Chae-Seok Lim, Xi Kang, Vincent Mirabella, Huaye Zhang, Qian Bu, Yoichi Araki, Elizabeth T Hoang, Shiqiang Wang, Ying Shen, Sukwoo Choi, Bong-Kiun Kaang, Qiang Chang, Zhiping P Pang, Richard L Huganir, J Julius Zhu
Rapid advances in genetics are linking mutations on genes to diseases at an exponential rate, yet characterizing the gene mutation-cell behavior relationships essential for precision medicine remains a daunting task. More than 350 mutations on small GTPase BRaf are associated with various tumors, and ∼40 mutations are associated with the neurodevelopmental disorder cardio-facio-cutaneous syndrome (CFC). We developed a fast cost-effective lentivirus-based rapid gene replacement method to interrogate the physiopathology of BRaf and ∼50 disease-linked BRaf mutants, including all CFC-linked mutants...
March 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28399683/kcnq2-associated-neonatal-epilepsy-phenotype-might-correlate-with-genotype
#20
Inn-Chi Lee, Jiann-Jou Yang, Jao-Shwann Liang, Tung-Ming Chang, Shuan-Yow Li
We analyzed the KCNQ2 wild-type gene and 3 mutations to highlight the important association between the KCNQ2 phenotype and genotype. The clinical phenotypes of 3 mutations (p.E515D, p.V543 M, and p.R213Q) were compared. KCNQ2, wild-type, and mutant KCNQ2 alleles were transfected into HEK293 cells before whole-cell patch-clamp analysis. Neurodevelopmental outcomes were worst in patients with the p.R213Q mutation, better in patients with the p.E515D mutation, and best in patients with the novel p.V543 M mutation...
January 1, 2017: Journal of Child Neurology
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