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https://www.readbyqxmd.com/read/29784875/a-human-specific-truncated-%C3%AE-7-nicotinic-receptor-subunit-assembles-with-full-length-%C3%AE-7-and-forms-functional-receptors-with-different-stoichiometries
#1
Matías Lasala, Jeremías Corradi, Ariana Bruzzone, María Del Carmen Esandi, Cecilia Bouzat
The cholinergic α7 nicotinic receptor gene, CHRNA7, encodes a subunit that forms the homopentameric α7 receptor, involved in learning and memory. In humans, exons 5-10 in CHRNA7 are duplicated and fused to the FAM7A genetic element, giving rise to the hybrid gene CHRFAM7A. Its product, dupα7, is a truncated subunit lacking part of the N-terminal extracellular ligand-binding domain and is associated with neurological disorders, including schizophrenia, and immunomodulation.We combined dupα7 expression on mammalian cells with patch clamp recordings to understand its functional role...
May 21, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29782847/optogenetic-induction-of-colonic-motility-in-mice
#2
Timothy J Hibberd, Jing Feng, Jialie Luo, Pu Yang, Vijay K Samineni, Robert W Gereau, Nigel Kelley, Hongzhen Hu, Nick J Spencer
BACKGROUND & AIMS: Strategies are needed to increase gastrointestinal transit without systemic pharmacologic agents. We investigated whether optogenetics, focal application of light to control enteric nervous system excitability, could be used to evoke propagating contractions and increase colonic transit in mice. METHODS: We generated transgenic mice with Cre-mediated expression of light-sensitive channelrhodopsin-2 (CHR2) in calretinin neurons (CAL-ChR2 Cre+ mice); Cre- littermates served as controls...
May 18, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29782051/the-novel-sodium-channel-modulator-gs-458967-gs967-is-an-effective-treatment-in-a-mouse-model-of-scn8a-encephalopathy
#3
Erin M Baker, Christopher H Thompson, Nicole A Hawkins, Jacy L Wagnon, Eric R Wengert, Manoj K Patel, Alfred L George, Miriam H Meisler, Jennifer A Kearney
OBJECTIVE: De novo mutations of SCN8A, encoding the voltage-gated sodium channel NaV 1.6, have been associated with a severe infant onset epileptic encephalopathy. Individuals with SCN8A encephalopathy have a mean age of seizure onset of 4-5 months, with multiple seizure types that are often refractory to treatment with available drugs. Anecdotal reports suggest that high-dose phenytoin is effective for some patients, but there are associated adverse effects and potential for toxicity...
May 21, 2018: Epilepsia
https://www.readbyqxmd.com/read/29781517/a-homozygous-scn5a-mutation-associated-with-atrial-standstill-and-sudden-death
#4
Reina Bianca Tan, Ivan Gando, Lei Bu, Frank Cecchin, William Coetzee
BACKGROUND: Atrial standstill is an arrhythmogenic condition characterized by the absence of spontaneous electrical and mechanical atrial activity or in response to stimulation. There are few reported familial cases which have been associated with SCN5A mutations co-segregating with GJA5 or RYR2 however isolated SCN5A mutations are rare. OBJECTIVE: The purpose of this study was to determine the clinical and biophysical consequence of a novel SCN5A mutation identified in a family with progressive atrial standstill and sudden death...
May 21, 2018: Pacing and Clinical Electrophysiology: PACE
https://www.readbyqxmd.com/read/29781252/subtype-selective-inhibition-of-acid-sensing-ion-channel-3-by-a-natural-flavonoid
#5
Xiao-Gang Yan, Wei-Guang Li, Xin Qi, Jia-Jie Zhu, Chen Huang, Shao-Ling Han, Qin Jiang, Tian-Le Xu, Jian-Hua Liu
AIMS: Acid-sensing ion channels (ASICs) are extracellular proton-gated cation channels that have been implicated in multiple physiological and pathological processes, and peripheral ASIC3 prominently participate into the pathogenesis of chronic pain, itch, and neuroinflammation, which necessitates the need for discovery and development of novel modulators in a subtype-specific manner. METHODS: Whole-cell patch clamp recordings and behavioral assays were used to examine the effect of several natural compounds on the ASIC-mediated currents and acid-induced nocifensive behavior, respectively...
May 20, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29779896/all-optical-electrophysiology-for-high-throughput-functional-characterization-of-a-human-ipsc-derived-motor-neuron-model-of-als
#6
Evangelos Kiskinis, Joel M Kralj, Peng Zou, Eli N Weinstein, Hongkang Zhang, Konstantinos Tsioras, Ole Wiskow, J Alberto Ortega, Kevin Eggan, Adam E Cohen
Human induced pluripotent stem cell (iPSC)-derived neurons are an attractive substrate for modeling disease, yet the heterogeneity of these cultures presents a challenge for functional characterization by manual patch-clamp electrophysiology. Here, we describe an optimized all-optical electrophysiology, "Optopatch," pipeline for high-throughput functional characterization of human iPSC-derived neuronal cultures. We demonstrate the method in a human iPSC-derived motor neuron (iPSC-MN) model of amyotrophic lateral sclerosis (ALS)...
May 11, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29779223/gene-editing-vectors-for-studying-nicotinic-acetylcholine-receptors-in-cholinergic-transmission
#7
Can Peng, Yijin Yan, Veronica J Kim, Staci E Engle, Jennifer N Berry, J Michael McIntosh, Rachael L Neve, Ryan M Drenan
Nicotinic acetylcholine receptors (nAChRs), prototype members of the cys-loop ligand gated ion channel family, are key mediators of cholinergic transmission in the central nervous system. Despite their importance, technical gaps exist in our ability to dissect the function of individual subunits in the brain. To overcome these barriers, we designed CRISPR/Cas9 small guide RNA sequences (sgRNAs) for production of loss-of-function alleles in mouse nAChR genes. These sgRNAs were validated in vitro via deep sequencing...
May 19, 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29778809/effects-of-propofol-on-ipscs-in-ca1-and-dentate-gyrus-cells-of-rat-hippocampus-propofol-effects-on-hippocampal-cells-ipscs
#8
Masanori Ishiguro, Suguru Kobayashi, Kiyoji Matsuyama, Takashi Nagamine
Propofol (2, 6-diisopropylphenol) is one of the most popular intravenous anesthetic agents. In this study, we compared the effects of propofol on inhibitory postsynaptic currents (IPSCs) induced by single and paired electrical stimulations in CA1 pyramidal cells (CA1-PCs) and dentate gyrus granule cells (DG-GCs) in rat hippocampal slices using the whole cell patch-clamp technique. In the absence of propofol, the amplitude of evoked IPSC by single stimulation and decay time constants were stable in both CA1-PCs and DG-GCs for 30 min...
May 17, 2018: Neuroscience Research
https://www.readbyqxmd.com/read/29778719/effect-of-heptanol-and-ethanol-on-excitation-wave-propagation-in-a-neonatal-rat-ventricular-myocyte-monolayer
#9
A D Podgurskaya, V A Tsvelaya, S R Frolova, I Y Kalita, N N Kudryashova, K I Agladze
In this work, the action of heptanol and ethanol was investigated in a two-dimensional (2D) model of cardiac tissue: the neonatal rat ventricular myocyte monolayer. Heptanol is known in electrophysiology as a gap junction uncoupler but may also inhibit voltage-gated ionic channels. Ethanol is often associated with the occurrence of arrhythmias. These substances influence sodium, calcium, and potassium channels, but the complete mechanism of action of heptanol and ethanol remains unknown. The optical mapping method was used to measure conduction velocities (CVs) in concentrations of 0...
May 17, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29777691/improving-electrical-properties-of-ipsc-cardiomyocytes-by-enhancing-cx43-expression
#10
Valentin Sottas, Carl-Mattheis Wahl, Mihnea C Trache, Michael Bartolf-Kopp, Sidney Cambridge, Markus Hecker, Nina D Ullrich
The therapeutic potential of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) is limited by immature functional features including low impulse propagation and reduced cell excitability. Key players regulating electrical activity are voltage-gated Na+ channels (Nav 1.5) and gap junctions built from connexin-43 (Cx43). Here we tested the hypothesis that enhanced Cx43 expression increases intercellular coupling and influences excitability by modulating Nav 1.5. Using transgenic approaches, Cx43 and Nav 1...
May 16, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29775644/redox-signal-mediated-trpm2-promotes-ang-ii-induced-adipocyte-insulin-resistance-via-ca-2-dependent-camkii-jnk-cascade
#11
Min Gao, Yu Du, Jing-Wen Xie, Jing Xue, Yi-Ting Wang, Li Qin, Ming-Ming Ma, Yong-Bo Tang, Xiao-Yan Li
BACKGROUND AND OBJECTIVE: Redox-sensitive transient receptor potential melastatin 2 (TRPM2) is a Ca2+ -permeable, nonselective cation channel which plays a crucial role in various physiological processes. However, little is known whether TRPM2 is involved in adipocyte dysfunction during hypertension. In the present study, we determined the role of TRPM2 in angiotensin II (Ang II)-induced insulin resistance in adipocytes and the underlying mechanisms. METHODS: Ang II-induced adipocyte insulin resistant model was conducted...
May 15, 2018: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29775559/mechanosensitivity-of-mitochondr-ial-large-conductance-calcium-activated-potassium-channels
#12
Agnieszka Walewska, Bogusz Kulawiak, Adam Szewczyk, Piotr Koprowski
Potassium channels have been discovered in the inner mitochondrial membrane of various cells. These channels can regulate the mitochondrial membrane potential, the matrix volume, respiration and reactive species generation. Therefore, it is believed that their activation is cytoprotective in various tissues. In our study, the single-channel activity of a large-conductance calcium-activated potassium channel (mitoBKCa ) was measured by the patch-clamp technique on mitoplasts derived from mitochondria isolated from human glioma U-87 MG cells...
May 15, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29774881/-effect-of-down-regulation-of-iks-repolarization-reserve-on-ventricular-arrhythmogenesis-in-a-guinea-pig-model-of-cardiac-hypertrophy
#13
Hegui Wang, Ting Huang, Zheng Wang, Nannan Ge, Yongsheng Ke
To observe the changes of rapidly activated delayed rectifier potassium channel (IKr) and slowly activated delayed rectifier potassium channel (IKs) in cardiac hypertrophy and to evaluate the effects of IKr and IKs blocker on the incidence of ventricular arrhythmias in guinea pigs with left ventricular hypertrophy (LVH).
 Methods: Guinea pigs were divided into a sham operation group and a left ventricular hypertrophy (LVH) group. LVH model was prepared. Whole cell patch-clamp technique was used to record IKr and IKs tail currents in a guinea pig model with LVH...
April 28, 2018: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/29774408/possible-association-of-cag-repeat-polymorphism-in-kcnn3-encoding-the-potassium-channel-sk3-with-oxaliplatin-induced-neurotoxicity
#14
Benjamin Anon, Bérenger Largeau, Alban Girault, Aurélie Chantome, Morgane Caulet, Clémence Perray, Driffa Moussata, Christophe Vandier, Chantal Barin-Le Guellec, Thierry Lecomte
INTRODUCTION: Data suggest a role of the potassium channel SK3 (KCNN3 gene) in oxaliplatin-induced neurotoxicity (OIN). Length variations in the polymorphic CAG repeat of the KCNN3 gene may be associated with the risk of OIN. MATERIALS AND METHODS: We performed patch-clamp experiments on HEK293 cell lines, expressing SK3 channel isoforms with short (11) or long (24) CAG repetitions, to measure intracellular calcium concentrations to test the effects of oxaliplatin on current density...
May 17, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29773582/activation-of-large-conductance-calcium-activated-k-channels-by-nitric-oxide-mediates-apelin-induced-relaxation-of-coronary-arteries
#15
Amreen Mughal, Chengwen Sun, Stephen T O'Rourke
Apelin increases coronary blood flow, cardiac contractility and cardiac output. Based on these favorable hemodynamic effects, apelin and apelin-like analogs are being developed for treating heart failure and related disorders; however, the molecular mechanisms underlying apelin-induced coronary vasodilation are unknown. This study aimed to elucidate the signaling pathways by which apelin causes smooth muscle relaxation in coronary arteries. Receptors for apelin (APJ receptors) were expressed in coronary arteries, as determined by Western blot and PCR analyses...
May 17, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29772528/peptide-inhibitors-of-chloride-channels-for-treating-secretory-diarrhea
#16
Jitu Ma, Xueqin Ding, Yulong Yin, Pengfei Huang
Morbidity and mortality associated with diarrheal diseases remain significant burdens on global health. In the developing world, the major sources of secretory diarrhea are infectious, including those caused by bacteria such as enterotoxic Escherichia coli , and viruses such as rotavirus. In many cases of secretory diarrhea, activation of pathways for cyclic nucleotides and/or Ca2+ signaling in the apical membrane of enterocytes increases the conductance of Cl- channels at the enterocyte lumen-facing membrane...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29772022/binding-of-sulphonylureas-to-plasma-proteins-a-katp-channel-perspective
#17
Peter Proks, Holger Kramer, Elizabeth Haythorne, Frances M Ashcroft
Sulphonylurea drugs stimulate insulin secretion from pancreatic β-cells primarily by inhibiting ATP sensitive potassium (KATP) channels in the β-cell membrane. The effective sulphonylurea concentration at its site of action is significantly attenuated by binding to serum albumin, which makes it difficult to compare in vitro and in vivo data. We therefore measured the ability of gliclazide and glibenclamide to inhibit KATP channels and stimulate insulin secretion in the presence of serum albumin. We used this data, together with estimates of free drug concentrations from binding studies, to predict the extent of sulphonylurea inhibition of KATP channels at therapeutic concentrations in vivo...
2018: PloS One
https://www.readbyqxmd.com/read/29769222/transient-outward-k-current-i-to-underlies-the-right-ventricular-initiation-of-polymorphic-ventricular-tachycardia-in-a-transgenic-rabbit-model-of-long-qt-syndrome-type-1
#18
Bum-Rak Choi, Weiyan Li, Dmitry Terentyev, Anatoli Y Kabakov, Mingwang Zhong, Colin M Rees, Radmila Terentyeva, Tae Yun Kim, Zhilin Qu, Xuwen Peng, Alain Karma, Gideon Koren
BACKGROUND: Sudden death in long-QT syndrome type 1 (LQT1), an inherited disease caused by loss-of-function mutations in KCNQ1, is triggered by early afterdepolarizations (EADs) that initiate polymorphic ventricular tachycardia (pVT). We investigated ionic mechanisms that underlie pVT in LQT1 using a transgenic rabbit model of LQT1. METHODS: Optical mapping, cellular patch clamping, and computer modeling were used to elucidate the mechanisms of EADs in transgenic LQT1 rabbits...
June 2018: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/29768434/plasma-membrane-insertion-of-kca2-3-sk3-is-dependent-upon-the-snare-proteins-syntaxin-4-and-snap23
#19
Claudia A Bertuccio, Tony T Wang, Kirk L Hamilton, Diego J Rodriguez-Gil, Steven B Condliffe, Daniel C Devor
We previously demonstrated endocytosis of KCa2.3 is caveolin-1-, dynamin II- and Rab5-dependent. KCa2.3 then enters Rab35/EPI64C- and RME-1-containing recycling endosomes and is returned to the plasma membrane (PM). Herein, we report on the mechanism by which KCa2.3 is inserted into the PM during recycling and following exit from the Golgi. We demonstrate KCa2.3 colocalizes with SNAP-23 and Syntaxin-4 in the PM of HEK and endothelial cells by confocal immunofluorescence microscopy. We further show KCa2.3 can be co-immunoprecipitated with SNAP-23 and Syntaxin-4...
2018: PloS One
https://www.readbyqxmd.com/read/29768271/direct-potentiation-of-capsaicin-current-by-histamine-and-its-effect-by-suplatast-on-rat-trigeminal-ganglia-neurons
#20
Jian-Rong Zhou, Tetsuya Shirasaki, Fumio Soeda, Kazumi Yokomizo, Kazuo Takahama
In this study, we investigated the effect of histamine on capsaicin-induced current and its influence by suplatast in rat trigeminal ganglia neurons using a patch-clamp technique. We found that histamine directly potentiated capsaicin-induced currents in rat sensory neurons, and suplatast had little effect on this potentiation. Since it has been known that suplatast suppresses histamine release from mast cells, it is possible that suplatast inhibits the activation of nociceptive fibers in the pathological condition via prevention of histamine-induced potentiation of the transient receptor potential vanilloid 1 receptor-mediated currents...
May 16, 2018: Pharmacology
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