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https://www.readbyqxmd.com/read/29775644/redox-signal-mediated-trpm2-promotes-ang-ii-induced-adipocyte-insulin-resistance-via-ca-2-dependent-camkii-jnk-cascade
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/29768258/multiple-actions-of-rotenone-an-inhibitor-of-mitochondrial-respiratory-chain-on-ionic-currents-and-miniature-end-plate-potential-in-mouse-hippocampal-mhippoe-14-neurons
#11
Chin-Wei Huang, Kao-Min Lin, Te-Yu Hung, Yao-Chung Chuang, Sheng-Nan Wu
BACKGROUND/AIMS: Rotenone (Rot) is known to suppress the activity of complex I in the mitochondrial chain reaction; however, whether this compound has effects on ion currents in neurons remains largely unexplored. METHODS: With the aid of patch-clamp technology and simulation modeling, the effects of Rot on membrane ion currents present in mHippoE-14 cells were investigated. RESULTS: Addition of Rot produced an inhibitory action on the peak amplitude of INa with an IC50 value of 39...
May 11, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29759541/the-phenotypic-spectrum-of-a-mutation-hotspot-responsible-for-the-short-qt-syndrome
#12
Dan Hu, Yang Li, Jiancheng Zhang, Ryan Pfeiffer, Michael H Gollob, Jeff Healey, Daniel Toshio Harrell, Naomasa Makita, Haruhiko Abe, Yaxun Sun, Jihong Guo, Li Zhang, Ganxin Yan, Douglas Mah, Edward P Walsh, Harris B Leopold, Carla Giustetto, Fiorenzo Gaita, Agnieszka Zienciuk-Krajka, Andrea Mazzanti, Silvia G Priori, Charles Antzelevitch, Hector Barajas-Martinez
OBJECTIVES: This study sought to evaluate the phenotypic and functional expression of an apparent hotspot mutation associated with short QT syndrome (SQTS). BACKGROUND: SQTS is a rare channelopathy associated with a high risk of life-threatening arrhythmias and sudden cardiac death (SCD). METHODS: Probands diagnosed with SQTS and their family members were evaluated clinically and genetically. KCNH2 wild-type (WT) and mutant genes were transiently expressed in HEK293 cells, and currents were recorded using whole-cell patch clamp and action potential (AP) clamp techniques...
July 2017: JACC. Clinical Electrophysiology
https://www.readbyqxmd.com/read/29758584/inhibition-of-sympathetic-sprouting-in-ccd-rats-by-lacosamide
#13
Yuying Wang, Fuquan Huo
BACKGROUND: Early hyperexcitability activity of injured nerve/neuron is critical for developing sympathetic nerve sprouting within dorsal root ganglia (DRG). Since lacosamide (LCM), an anticonvulsant, inhibits Na+ channel. The present study tried to test the potential effect of LCM on inhibiting sympathetic sprouting in vivo. METHODS: LCM (50 mg/kg) was daily injected intraperitoneally into rats subjected to chronic compression DRG (CCD), an animal model of neuropathic pain that exhibits sympathetic nerve sprouting, for the 1st 7 days after injury...
May 14, 2018: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/29758359/probing-flecainide-block-of-i-na-using-human-pluripotent-stem-cell-derived-ventricular-cardiomyocytes-adapted-to-automated-patch-clamping-and-2d-monolayers
#14
Lin Geng, Chi-Wing Kong, Andy O T Won, Angie Man-Yee Shum, Maggie Z Y Chow, Hui Che, Chenzi Zhang, Ka-Long Yau, Camie W Chan, Wendy Keung, Ronald A Li
Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) are emerging tools for applications such as drug discovery and screening for pro-arrhythmogenicity and cardiotoxicity as leading causes for drug attrition. Understanding the electrophysiology (EP) of hPSC-CMs is essential but conventional manual patch-clamping is highly laborious and low-throughput. Here we adapted hPSC-CMs derived from two human embryonic stem cell (hESC) lines, HES2 and H7, for a 16-channel automated planar-recording approach for single-cell EP characterization...
May 11, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29758302/plasminogen-binding-inhibitors-demonstrate-unwanted-activities-on-gaba-a-and-glycine-receptors-in-human-ipsc-derived-neurons
#15
Lisbeth Kristensson, Anders Lundin, David Gustafsson, Jan Fryklund, Tomas Fex, Delsing Louise, Erik Ryberg
Plasminogen binding inhibitors (PBIs) reduce the risk of bleeding in hemorrhagic conditions. However, generic PBIs are also associated with an increased risk of seizures, an adverse effect linked to unwanted activities towards inhibitory neuronal receptors. Development of novel PBIs serve to remove compounds with such properties, but progress is limited by a lack of higher throughput methods with human translatability. Herein we apply human induced pluripotent stem cell (hiPSC) derived neurons in combination with dynamic mass redistribution (DMR) technology to demonstrate robust and reproducible modulation of both GABAA and glycine receptors...
May 11, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29757278/a-microbiomechanical-system-for-studying-varicosity-formation-and-recovery-in-central-neuron-axons
#16
Dustin Servello, Yuanzheng Gu, Chen Gu
Axonal varicosities are enlarged structures along the shafts of axons with a high degree of heterogeneity. They are present not only in brains with neurodegenerative diseases or injuries, but also in the normal brain. Here, we describe a newly-established micromechanical system to rapidly, reliably, and reversibly induce axonal varicosities, allowing us to understand the mechanisms governing varicosity formation and heterogeneous protein composition. This system represents a novel means to evaluate the effects of compression and shear stress on different subcellular compartments of neurons, different from other in vitro systems that mainly focus on the effect of stretching...
April 30, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29755550/the-effects-of-buthotus-schach-scorpion-venom-on-electrophysiological-properties-of-magnocellular-neurons-of-rat-supraoptic-nucleus
#17
Akram Aboutorabi, Nima Naderi, Hamid Gholami Pourbadie, Hossein Zolfagharian, Hossein Vatanpour
Bothutous Schach  (BS) scorpion venom consists of several polypeptides that could modulate ion channels. In this study, the effects of BS crude venom on passive and active electrophysiological properties of rat neurons in supraoptic nucleus (SON) of hypothalamus was investigated using whole-cell patch clamp technique. The results showed that bath application of BS venom produced significant change in passive properties of SON neurons, namely a decrease in resting membrane potential and an increase in input resistance of the cells...
2018: Iranian Journal of Pharmaceutical Research: IJPR
https://www.readbyqxmd.com/read/29752983/orexin-b-modulates-spontaneous-excitatory-and-inhibitory-transmission-in-lamina-ii-neurons-of-adult-rat-spinal-cord
#18
Chong Wang, Tsugumi Fujita, Eiichi Kumamoto
Cellular mechanisms underlying the antinociceptive properties of orexins, a group of neuropeptides produced by the hypothalamus, in the spinal dorsal horn have not been thoroughly investigated. We examined how orexin B affects spontaneous synaptic transmission in lamina II neurons, which play a pivotal role in regulating nociceptive transmission, by applying a whole-cell patch-clamp technique to lamina II neurons in adult rat spinal cord slices. In 66% of neurons tested, bath-applied orexin B concentration-dependently produced an inward current at -70 mV and/or increased the frequency of glutamatergic spontaneous excitatory postsynaptic current (sEPSC) without changing its amplitude, in a manner resistant to the voltage-gated Na+ -channel blocker tetrodotoxin...
May 9, 2018: Neuroscience
https://www.readbyqxmd.com/read/29752414/ligand-binding-and-activation-properties-of-the-purified-bacterial-cyclic-nucleotide-gated-channel-sthk
#19
Philipp A M Schmidpeter, Xiaolong Gao, Vikrant Uphadyay, Jan Rheinberger, Crina M Nimigean
Cyclic nucleotide-modulated ion channels play several essential physiological roles. They are involved in signal transduction in photoreceptors and olfactory sensory neurons as well as pacemaking activity in the heart and brain. Investigations of the molecular mechanism of their actions, including structural and electrophysiological characterization, are restricted by the availability of stable, purified protein obtained from accessible systems. Here, we establish that SthK, a cyclic nucleotide-gated (CNG) channel from Spirochaeta thermophila , is an excellent model for investigating the gating of eukaryotic CNG channels at the molecular level...
May 11, 2018: Journal of General Physiology
https://www.readbyqxmd.com/read/29752336/the-role-and-mechanism-of-chaperones-calnexin-calreticulin-in-which-alln-selectively-rescues-the-trafficking-defective-of-herg-a561v-mutation
#20
Ying Wang, Tingting Shen, Peiliang Fang, Junbo Zhou, Kenan Lou, Zemin Cen, Hai Qian, Jianqing Zhou, Ningsheng Liu, Jiangfang Lian
Background: LQT2 was caused by HERG mutation. L539fs/47 encodes a truncated protein,and its mechanisms in HERG mutation is unknown. Method: HERG mutation plasmids were overexpressed in HEK293T cells respectively, followed by analyzing lysates with western-blot. Transfected HEK293T cells were treated with or without ALLN and Propranolol 24hrs or 48hrs. HERG-WT, HERG-A561V, WT/A561V, HERG-L539fs/47, WT/L539fs/47 and calnexin/calreticulin protein expressing and their interactions were detected by western blot and immunoprecipitation...
May 11, 2018: Bioscience Reports
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