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Potassium current voltage clamp

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https://www.readbyqxmd.com/read/28327344/direct-activation-of-ca-2-and-voltage-gated-potassium-channels-of-large-conductance-by-anandamide-in-endothelial-cells-does-not-support-the-presence-of-endothelial-atypical-cannabinoid-receptor
#1
Alexander I Bondarenko, Olga Panasiuk, Iryna Okhai, Fabrizio Montecucco, Karim J Brandt, Francois Mach
Endocannabinoid anandamide induces endothelium-dependent relaxation commonly attributed to stimulation of the G-protein coupled endothelial anandamide receptor. The study addressed the receptor-independent effect of anandamide on large conductance Ca(2+)-dependent K(+) channels expressed in endothelial cell line EA.hy926. Under resting conditions, 10µM anandamide did not significantly influence the resting membrane potential. In a Ca(2+)-free solution the cells were depolarized by ~10 mV. Further administration of 10µM anandamide hyperpolarized the cells by ~8 mV...
March 19, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28325748/halogenated-ether-alcohol-and-alkane-anesthetics-activate-task-3-tandem-pore-potassium-channels-likely-through-a-common-mechanism
#2
Anita Luethy, James D Boghosian, Rithu Srikantha, Joseph Cotten
TASK-3 (KCNK9) tandem pore potassium channel function is activated by halogenated anesthetics through binding at a putative anesthetic binding cavity. To understand pharmacological requirements for TASK-3 activation, we studied the concentration-response of TASK-3 to several anesthetics (isoflurane, desflurane, sevoflurane, halothane, α-chloralose, 2,2,2-trichloroethanol(TCE), and chloral hydrate), to ethanol, and to a panel of halogenated methanes and alcohols. We used mutagenesis to probe the anesthetic binding cavity as observed in a TASK-3 homology model...
March 21, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28315292/hypoxic-culture-promotes-dopaminergic-neuronal-differentiation-of-nasal-olfactory-mucosa-mesenchymal-stem-cells-via-up-regulation-of-hypoxia-inducible-factor-1%C3%AE
#3
Yi Zhuo, Lei Wang, Lite Ge, Xuan Li, Ping Chen, Da Duan, Xiaohua Teng, Miao Jiang, Kai Liu, Ting Yuan, Pei Wu, Hao Wang, Yujia Deng, Huali Xie, Ying Xia, Ming Lu
<p><b>Background</b> Olfactory mucosa mesenchymal stem cells (OM-MSCs) display significant clonogenicactivity and may be easily propagated for Parkinson's disease therapies. Methods of inducing OM-MSCs to differentiate into dopaminergic (DAergic) neurons using olfactory ensheathing cells (OECs) is thus an attractive topic of research.</p><p><b>Methods</b> We designed a hypoxic-induction protocol to generate DAergic neurons from OM-MSCs using a physiological oxygen (O2) level of 3% and OEC-conditioned medium (HI group)...
March 17, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28306530/ascorbic-acid-does-not-modulate-potassium-currents-in-cultured-human-lymphocytes
#4
Saravanakumar Snekalatha, Praghalathan Kanthakumar
BACKGROUND: Ascorbic acid (AA) is known to modulate lymphocyte function, but the mechanism of action is not clearly understood. As voltage-gated potassium currents play an important role in lymphocyte function, the effect of AA on voltage-gated potassium currents was studied. METHODS: Peripheral blood mononuclear cells were cultured in the presence of increasing concentrations of AA (0, 0.125, 0.25, 0.5, and 1 mM). Potassium currents in resting lymphocytes were studied by whole cell patch clamp technique using a depolarizing protocol...
March 17, 2017: Journal of Basic and Clinical Physiology and Pharmacology
https://www.readbyqxmd.com/read/28288868/inhibition-of-kir4-1-potassium-channels-by-quinacrine
#5
Leticia G Marmolejo-Murillo, Iván A Aréchiga-Figueroa, Meng Cui, Eloy G Moreno-Galindo, Ricardo A Navarro-Polanco, José A Sánchez-Chapula, Tania Ferrer, Aldo A Rodríguez Menchaca
Inwardly rectifying potassium (Kir) channels are expressed in many cell types and contribute to a wide range of physiological processes. Particularly, Kir4.1 channels are involved in the astroglial spatial potassium buffering. In this work, we examined the effects of the cationic amphiphilic drug quinacrine on Kir4.1 channels heterologously expressed in HEK293 cells, employing the patch clamp technique. Quinacrine inhibited the currents of Kir4.1 channels in a concentration and voltage dependent manner. In inside-out patches, quinacrine inhibited Kir4...
March 10, 2017: Brain Research
https://www.readbyqxmd.com/read/28282785/peimine-inhibits-herg-potassium-channels-through-the-channel-inactivation-states
#6
Liandi Kan, Wei Zhao, Lanying Pan, Jianwei Xu, Qingmao Chen, Kai Xu, Liping Xiao, Yuan Chen
BACKGROUND AND OBJECTIVE: Fritillaria is a Chinese traditional herb. It has a long history and many medicinal usages including antitussive, anti-inflammatory and pain relieving actions. It is also used as food. However, its cardiac safety has not been tested. Peimine is one of the main active compounds of Fritillaria. To be listed as an herb in the Chinese Pharmacopoeia, a special minimal percentage of Peimine in the dry sample of Fritillaria is required. The main concern for cardiac safety determination is the possible inhibition of hERG ion channels...
March 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28265686/inhibition-of-cloned-herg-potassium-channels-by-risperidone-and-paliperidone
#7
Hong Joon Lee, Jin-Sung Choi, Bok Hee Choi, Sang June Hahn
Risperidone and one of its active metabolites, paliperidone, are widely used for the treatment of schizophrenia. We used a patch-clamp study to investigate the effects of paliperidone on hERG potassium channels expressed in HEK cells. Western blot analyses were used to study the effects of risperidone and paliperidone on hERG and hERG 3.1 isoform channel trafficking. Risperidone and paliperidone inhibited the hERG tail currents in a concentration-dependent manner with IC50 values of 0.16 and 0.57 μM, respectively...
March 6, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28262417/cell-autonomous-excitation-of-midbrain-dopamine-neurons-by-endocannabinoid-dependent-lipid-signaling
#8
Stephanie C Gantz, Bruce P Bean
The major endocannabinoid in the mammalian brain is the bioactive lipid 2-arachidonoylglycerol (2-AG). The best-known effects of 2-AG are mediated by G-protein-coupled cannabinoid receptors. In principle, 2-AG could modify neuronal excitability by acting directly on ion channels, but such mechanisms are poorly understood. Using a preparation of dissociated mouse midbrain dopamine neurons to isolate effects on intrinsic excitability, we found that 100 nM 2-AG accelerated pacemaking and steepened the frequency-current relationship for burst-like firing...
March 22, 2017: Neuron
https://www.readbyqxmd.com/read/28248535/bis-3-tacrine-inhibits-the-sustained-potassium-current-in-cultured-rat-hippocampal-neurons
#9
D Huang, R-J Wen, Y Zhang, Y-W Liu
Bis(3)-tacrine is a dimeric AChE inhibitor derived from tacrine with a potential to treat Alzheimer's disease. It was recently been reported to act as a fast off-rate antagonist of NMDA receptors with moderate affinity. In the present study, we aimed to explore whether bis(3)-tacrine could modulate the function of native sustained potassium current in cultured rat hippocampal neurons using whole-cell patch-clamp technique. We found that bis(3)-tacrine inhibited the amplitude of sustained potassium current in a reversible and concentration-dependent manner, with a potency two orders of magnitude higher than that of tacrine...
February 28, 2017: Physiological Research
https://www.readbyqxmd.com/read/28242439/kv3-1-kv3-2-channel-positive-modulators-enable-faster-activating-kinetics-and-increase-firing-frequency-in-fast-spiking-gabaergic-interneurons
#10
Kim Boddum, Charlotte Hougaard, Julie Xiao-Ying Lin, Nadia Lybøl von Schoubye, Henrik Sindal Jensen, Morten Grunnet, Thomas Jespersen
Due to their fast kinetic properties, Kv3.1 voltage gated potassium channels are important in setting and controlling firing frequency in neurons and pivotal in generating high frequency firing of interneurons. Pharmacological activation of Kv3.1 channels may possess therapeutic potential for treatment of epilepsy, hearing disorders, schizophrenia and cognitive impairments. Here we thoroughly investigate the selectivity and positive modulation of the two small molecules, EX15 and RE01, on Kv3 channels. Selectivity studies, conducted in Xenopus laevis oocytes confirmed a positive modulatory effect of the two compounds on Kv3...
February 24, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28228734/%C3%AE-subunits-functionally-differentiate-human-kv4-3-potassium-channel-splice-variants
#11
Geoffrey W Abbott
The human ventricular cardiomyocyte transient outward K(+) current (Ito) mediates the initial phase of myocyte repolarization and its disruption is implicated in Brugada Syndrome and heart failure (HF). Human cardiac Ito is generated primarily by two Kv4.3 splice variants (Kv4.3L and Kv4.3S, diverging only by a C-terminal, S6-proximal, 19-residue stretch unique to Kv4.3L), which are differentially remodeled in HF, but considered functionally alike at baseline. Kv4.3 is regulated in human heart by β subunits including KChIP2b and KCNEs, but their effects were previously assumed to be Kv4...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28197715/vacuolar-ion-channels-in-the-liverwort-marchantia-polymorpha-influence-of-ion-channel-inhibitors
#12
Mateusz Koselski, Kazimierz Trebacz, Halina Dziubinska
Potassium-permeable slow activating vacuolar channels (SV) and chloride-permeable channels in the vacuole of the liverwort Marchantia polymorpha were characterized in respect to calcium dependence, selectivity, and pharmacology. The patch-clamp method was used in the study of ion channel activity in the vacuoles from the liverwort Marchantia polymorpha. The whole-vacuole recordings allowed simultaneous observation of two types of currents-predominant slow activated currents recorded at positive voltages and fast activated currents recorded at negative voltages...
February 14, 2017: Planta
https://www.readbyqxmd.com/read/28119399/an-als-associated-mutant-sod1-rapidly-suppresses-kcnt1-slack-na-activated-k-channels-in-aplysia-neurons
#13
Yalan Zhang, Weiming Ni, Arthur L Horwich, Leonard K Kaczmarek
Mutations that alter levels of Slack (KCNT1) Na(+)-activated K(+) current produce devastating effects on neuronal development and neuronal function. We now find that Slack currents are rapidly suppressed by oligomers of mutant human Cu/Zn superoxide dismutase 1 (SOD1), which are associated with motor neuron toxicity in an inherited form of amyotrophic lateral sclerosis (ALS). We recorded from bag cell neurons of Aplysia californica, a model system to study neuronal excitability. We found that injection of fluorescent wild-type SOD1 (wt SOD1YFP) or monomeric mutant G85R SOD1YFP had no effect on net ionic currents measured under voltage clamp...
February 22, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28119170/existence-of-atp-sensitive-potassium-currents-on-human-periodontal-ligament-cells
#14
Phuong Thi Huyen Tran, Young Hee Lee, Janardhan Prasad Bhattarai, Soo Joung Park, Ho-Keun Yi, Seong Kyu Han
OBJECTIVE: Potassium channels of the ATP-sensitive family (KATP channel) are inhibited by increase in intracellular ATP. Electrophysiological studies have demonstrated that the kinetics and pharmacological properties of KATP channels vary among different tissues, suggesting structurally and functionally distinct types. There are studies showing human periodontal ligament (PDL) cells respond to mechanical stress by increasing ATP release, which participates in bone resorption or bone homeostasis...
January 17, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28096388/competition-of-calcified-calmodulin-n-lobe-and-pip2-to-an-lqt-mutation-site-in-kv7-1-channel
#15
William Sam Tobelaim, Meidan Dvir, Guy Lebel, Meng Cui, Tal Buki, Asher Peretz, Milit Marom, Yoni Haitin, Diomedes E Logothetis, Joel Alan Hirsch, Bernard Attali
Voltage-gated potassium 7.1 (Kv7.1) channel and KCNE1 protein coassembly forms the slow potassium current IKS that repolarizes the cardiac action potential. The physiological importance of the IKS channel is underscored by the existence of mutations in human Kv7.1 and KCNE1 genes, which cause cardiac arrhythmias, such as the long-QT syndrome (LQT) and atrial fibrillation. The proximal Kv7.1 C terminus (CT) binds calmodulin (CaM) and phosphatidylinositol-4,5-bisphosphate (PIP2), but the role of CaM in channel function is still unclear, and its possible interaction with PIP2 is unknown...
January 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28075010/stimulatory-actions-of-a-novel-thiourea-derivative-on-large-conductance-calcium-activated-potassium-channels
#16
Sheng-Nan Wu, Jyh-Haur Chern, Santai Shen, Hwei-Hisen Chen, Ying-Ting Hsu, Chih-Chin Lee, Ming-Huan Chan, Ming-Chi Lai, Feng-Shiun Shie
AIM: In this study, we examine whether an anti-inflammatory thiourea derivative, compound #326, actions on ion channels. METHODS: The effects of compound #326 on Ca(2+) -activated K(+) channels were evaluated by patch-clamp recordings obtained in cell-attached, inside-out or whole-cell configuration. RESULTS: In pituitary GH3 cells, compound #326 increased the amplitude of Ca(2+) -activated K(+) currents (IK(Ca) ) with an EC50 value of 11...
January 11, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28072464/genistein-and-tyrphostin-ag556-decrease-ultra-rapidly-activating-delayed-rectifier-k-current-of-human-atria-by-inhibiting-egf-receptor-tyrosine-kinase
#17
Guo-Sheng Xiao, Yan-Hui Zhang, Wei Wu, Hai-Ying Sun, Yan Wang, Gui-Rong Li
BACKGROUND AND PURPOSE: The ultra-rapidly activating delayed rectifier K(+) current IKur (encoded by Kv 1.5 or KCNA5) plays an important role in human atrial repolarization. The present study investigates the regulation of this current by protein tyrosine kinases (PTKs). EXPERIMENTAL APPROACH: Whole-cell patch voltage clamp technique and immunoprecipitation and Western blotting analysis were used to investigate whether the PTK inhibitors genistein, tyrphostin AG556 (AG556) and PP2 regulate human atrial IKur and hKv1...
March 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28066143/acepromazine-inhibits-herg-potassium-ion-channels-expressed-in-human-embryonic-kidney-293-cells
#18
Young Shin Joo, Hong Joon Lee, Jin-Sung Choi, Ki-Wug Sung
The effects of acepromazine on human ether-à-go-go-related gene (hERG) potassium channels were investigated using whole-cell voltage-clamp technique in human embryonic kidney (HEK293) cells transfected with hERG. The hERG currents were recorded with or without acepromazine, and the steady-state and peak tail currents were analyzed for the evaluating the drug effects. Acepromazine inhibited the hERG currents in a concentration-dependent manner with an IC50 value of 1.5 µM and Hill coefficient of 1.1. Acepromazine blocked hERG currents in a voltage-dependent manner between -40 and +10 mV...
January 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28058990/restoration-of-the-response-of-the-middle-cerebral-artery-of-the-rat-to-acidosis-in-hyposmotic-hyponatremia-by-the-opener-of-large-conductance-calcium-sensitive-potassium-channels-bkca
#19
Marta Aleksandrowicz, Beata Dworakowska, Krzysztof Dolowy, Ewa Kozniewska
Hyposmotic hyponatremia (the decrease of extracellular concentration of sodium ions from 145 to 121 mM and the decrease of hyposmolality from 300 to 250 mOsm/kg H2O) impairs response of the middle cerebral artery (MCA) to acetylcholine and NO donor (S-nitroso-N-acetyl-DL-penicillamine). Since acidosis activates a similar intracellular signaling pathway, the present study was designed to verify the hypothesis that the response of the MCA to acidosis is impaired during acute hyposmotic hyponatremia due to abnormal NO-related signal transduction in vascular smooth muscle cells...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28056022/l-type-calcium-channel-inhibition-contributes-to-the-proarrhythmic-effects-of-aconitine-in-human-cardiomyocytes
#20
Jianjun Wu, Xiangchong Wang, Ying Ying Chung, Cai Hong Koh, Zhenfeng Liu, Huicai Guo, Qiang Yuan, Chuan Wang, Suwen Su, Heming Wei
Aconitine (ACO) is well-known for causing lethal ventricular tachyarrhythmias. While cardiac Na+ channel opening during repolarization has long been documented in animal cardiac myocytes, the cellular effects and mechanism of ACO in human remain unexplored. This study aimed to assess the proarrhythmic effects of ACO in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). ACO concentration-dependently (0.3 ~ 3.0 μM) shortened the action potentials (AP) durations (APD) in ventricular-like hiPSC-CMs by > 40% and induced delayed after-depolarization...
2017: PloS One
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