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Potassium Channels

Isabel D Derera, Katalin Cs Smith, Bret N Smith
Sudden unexpected death in epilepsy (SUDEP) is among the leading causes of death in people with epilepsy. Individuals with temporal lobe epilepsy (TLE) have a high risk for SUDEP because the seizures are often medically intractable. Neurons in the nucleus tractus solitarius (NTS) have been implicated in mouse models of SUDEP and play a critical role in modulating cardiorespiratory and autonomic output. Increased neuronal excitability of inhibitory, GABAergic neurons in the NTS develops during epileptogenesis and NTS dysfunction has been implicated in mouse models of SUDEP...
December 5, 2018: Journal of Neurophysiology
Sandra A Jones, Richard D Walton, Michael Morton, Matthew K Lancaster
INTRODUCTION: K2p 3.1, also known as TASK-1, is a twin-pore acid-sensitive repolarizing K+ channel, responsible for a background potassium current that significantly contributes to setting the resting membrane potential of cardiac myocytes. Inhibition of IK2p3.1 alters cardiac repolarization and is pro-arrhythmogenic. In this study, we have examined the expression of K2p 3.1 and function of this channel in tissue and myocytes from across the left ventricular free wall. METHODS AND RESULTS: Using fluorescence immunocytochemistry, the expression of K2p 3...
December 5, 2018: Journal of Cardiovascular Electrophysiology
Didhiti Mukherjee, Greta Sokoloff, Mark S Blumberg
In week-old rats, somatosensory input arises predominantly from external stimuli or from sensory feedback (reafference) associated with myoclonic twitches during active sleep. A previous study suggested that the brainstem motor structures that produce twitches also send motor copies (or corollary discharge, CD) to the cerebellum. We tested this possibility by recording from two precerebellar nuclei-the inferior olive (IO) and lateral reticular nucleus (LRN). In most IO and LRN neurons, twitch-related activity peaked sharply around twitch onset, consistent with CD...
December 5, 2018: ELife
Qiang Wu, Guihua Wei, Fengtao Ji, Shushan Jia, Shaogen Wu, Xinying Guo, Long He, Zhiqiang Pan, Xuerong Miao, Qingxiang Mao, Yong Yang, Minghui Cao, Yuan-Xiang Tao
Peripheral nerve injury downregulates the expression of the μ-opioid receptor (MOR) and voltage-gated potassium channel subunit Kv1.2 by increasing their DNA methylation in the dorsal root ganglion (DRG). Ten-eleven translocation methylcytosine dioxygenase 1 (TET1) causes DNA demethylation. Given that DRG MOR and Kv1.2 downregulation contribute to neuropathic pain genesis, this study investigated the effect of DRG TET1 overexpression on neuropathic pain. Overexpression of TET1 in the DRG through microinjection of herpes simplex virus expressing full-length TET1 mRNA into the injured rat DRG significantly alleviated the fifth lumbar spinal nerve ligation (SNL)-induced pain hypersensitivities during the development and maintenance periods, without altering acute pain or locomotor function...
December 4, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Nisha Panth, Keshav Raj Paudel, Dal-Seong Gong, Min-Ho Oak
Morus alba (white mulberry) is native to the northern part of Korea and popularly used as a traditional medicine due to its numerous health benefits against human's disease. However, the possibility that M. alba may also affect the cardiovascular system remains unexplored. This study sought to investigate the vascular protective effects of the root bark extract of M. alba (MAE). Vascular reactivity was performed in organ baths using isolated rat thoracic aorta, while platelet derived growth factor (PDGF) induced proliferation and migration of vascular smooth muscle cells (VSMCs) were studied by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) and wound healing assay, respectively...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
Xiao-Yan Wu, Xue-Yan Yu
KCNJ4 (potassium voltage-gated channel subfamily J member 4) belongs to the inward rectifier potassium channel family, which is inhibited by novel anticancer agents. However, the biologic significance of KCNJ4 in lung adenocarcinoma (LADC) is largely unknown. Therefore, in this study, we evaluated the expression, clinical correlation, and prognostic value of KCNJ4 in LADC and normal lung tissues according to data from The Cancer Genome Atlas datasets. A small interfering RNA (siRNA)-mediated technology was used to inhibit the expression level of KCNJ4...
December 4, 2018: Journal of Biochemical and Molecular Toxicology
Kailin Zhang, Hong Jiang, Nan Li
Genetic generalized epilepsies (GGEs) are a group of epilepsy syndromes caused by genetic factors. A few of GGEs conform to the Mendelian patterns, while most of them show polygene inheritance. Researchers initially found that most of the genes associated with GGEs are related to ion channels including voltage-gated sodium channels, potassium channels, calcium channels and chloride channels, and ligand-gated gamma-aminobutyric acid receptor channels. Further researches have shown that certain non-ion channel genes are also related to GGEs, and that de novo mutations and copy number variants also play an important role in the pathogenesis of GGEs...
December 10, 2018: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
Chen Lu, Xu Huang, Hong-Li Lu, Shao-Hua Liu, Jing-Yu Zang, Yu-Jia Li, Jie Chen, Wen-Xie Xu
AIM: To investigate the distribution and function of interstitial cells of Cajal (ICCs) and platelet-derived growth factor receptor-α positive (PDGFRα+ ) cells in the proximal and distal colon. METHODS: The comparison of colonic transit in the proximal and distal ends was performed by colonic migrating motor complexes (CMMCs). The tension of the colonic smooth muscle was examined by smooth muscle spontaneous contractile experiments with both ends of the smooth muscle strip tied with a silk thread...
November 28, 2018: World Journal of Gastroenterology: WJG
Masayuki Iwamoto, Shigetoshi Oiki
Molecular mechanisms underlying channel-membrane interplay have been extensively studied. Cholesterol, as a major component of the cell membrane, participates either in specific binding to channels or via modification of membrane physical features. Here, we examined the action of various sterols (cholesterol, epicholesterol, etc.) on a prototypical potassium channel (KcsA). Single-channel current recordings of the KcsA channel were performed in a water-in-oil droplet bilayer (contact bubble bilayer) with a mixed phospholipid composition (azolectin)...
December 3, 2018: Proceedings of the National Academy of Sciences of the United States of America
Ning Song, Da-Qing Liao, Fei Liu, Yan-Yan Zhang, Jiu Lin, Hang Wang, Jie-Fei Shen
PURPOSE: Titanium (Ti) is the key material used in dental implants because of its excellent biocompatibility. But wear and corrosion Ti particles had been widely reported to induce inflammation and promote bone absorption. However, little information is known about the damage of Ti particles on neurons. MATERIALS AND METHODS: Trigeminal root ganglion (TRG) neurons were exposed to Ti particles (<5 μm). The electrophysiological properties of 2 main subtypes of voltage-gated potassium channels (VGPCs) (KA and KV) were examined by whole-cell patch-clamp techniques...
November 30, 2018: Implant Dentistry
Christopher M Hearon, Jennifer C Richards, Mathew L Racine, Gary J Luckasen, Dennis G Larson, Frank A Dinenno
KEY POINTS: In humans, the vasodilatory response to skeletal muscle contraction is mediated in part by activation of inwardly rectifying potassium (KIR ) channels. Evidence from animal models suggest that KIR channels serve as electrical amplifiers of endothelium-dependent hyperpolarization (EDH). We found that skeletal muscle contraction amplifies vasodilatation to the endothelium-dependent agonist acetylcholine (ACh), whereas there was no change in the vasodilatory response to sodium nitroprusside, an endothelium-independent nitric oxide donor...
December 1, 2018: Journal of Physiology
Shigeki Sugawara
Silurus asotus egg lectin (SAL) is an α-galactoside-binding protein, isolated from the egg of catfish. It belongs to the rhamnose-binding lectin family that binds to Gb3 glycan (Galα1-4Galβ1-4Glc). SAL has resulted in the induction of early apoptosis in the Raji cell line, which is a Burkitt's lymphoma cell line expressing Gb3. The apoptosis was characterized by i) increased externalization of phosphatidylserin via multidrug resistance 1 P-glycoprotein (MDR1 P-gp), and ii) reduced cell size through the activation of voltage-gated potassium channel Kv1...
2018: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
Anna R Parker, Lori A Forster, Deborah J Baro
Neurons operate within defined activity limits, and feedback control mechanisms dynamically tune ionic currents to maintain this optimal range. This study describes a novel, rapid feedback mechanism that uses SUMOylation to continuously adjust ionic current densities according to changes in activity. <u>S</u>mall <u>U</u>biquitin-like <u>MO</u>difier (SUMO) is a peptide that can be post-translationally conjugated to ion channels to influence their surface expression and biophysical properties...
November 30, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Zhongwei Xiong, Kai Zhang, Tamaki Ishima, Qian Ren, Min Ma, Yaoyu Pu, Lijia Chang, Jincao Chen, Kenji Hashimoto
A recent study demonstrated a key role of astroglial potassium channel Kir4.1 in the lateral habenula in depression. We investigated whether Kir4.1 protein is altered in the brain regions from susceptible mice after a chronic social defeat stress (CSDS). Furthermore, we compared the rapid and sustained antidepressant actions of Kir4.1 inhibitors (quinacrine and sertraline) and (R)-ketamine, (R)-enantiomer of rapid-acting antidepressant (R,S)-ketamine, in a CSDS model. Western blot analysis of Kir4.1 protein in the brain regions (prefrontal cortex, nucleus accumbens, hippocampus) from CSDS susceptible mice and control mice (no CSDS) was performed...
November 28, 2018: Pharmacology, Biochemistry, and Behavior
P Tulay, S G Temel, M C Ergoren
Potassium channels are important in transmitting electrical signals through potassium ions transport. These potassium channels are made from signals encoded by KCNQ1 gene. KCNQ1 polymorphisms were associated with many diseases, including many metabolic and cardiovascular diseases and therefore they can be employed as biomarkers. In this study we aimed to investigate KCNQ1 polymorphisms in the Turkish Cypriot population to reveal the allele frequencies specific for this population and use these polymorphisms as biomarkers to develop preventative medical measures...
November 27, 2018: International Journal of Biological Macromolecules
Daniel T Infield, Kimberly Matulef, Jason D Galpin, Kin Lam, Emad Tajkhorshid, Christopher A Ahern, Francis I Valiyaveetil
Membrane proteins are universal signal decoders. The helical transmembrane segments of these proteins play central roles in sensory transduction, yet the mechanistic contributions of secondary structure remain unresolved. To investigate the role of main-chain hydrogen bonding on transmembrane function, we encoded amide-to-ester substitutions at sites throughout the S4 voltage-sensing segment of Shaker potassium channels, a region that undergoes rapid, voltage-driven movement during channel gating. Functional measurements of ester-harboring channels highlight a transitional region between α-helical and 310 segments where hydrogen bond removal is particularly disruptive to voltage-gating...
November 29, 2018: Nature Communications
Barbara Correia, Robert D Hancock, Luis Valledor, Glória Pinto
Previous knowledge suggested the involvement of specific pathways/proteins that could be identified as potential molecular indicators linked to enhanced drought tolerance in Eucalyptus globulus. Here, we looked for specific variations in key transcripts of two Eucalyptus globulus clones (AL-18 and AL-13) exposed to water deficit and rehydration with two main goals: (i) to check if and how transcripts potentially associated with stress response and protection are modulated in a controlled experiment; and (ii) to verify if the transcript response is robust in a field case study...
November 1, 2018: Tree Physiology
A Herpain, S Bouchez, M Girardis, F Guarracino, J Knotzer, B Levy, T Liebregts, P Pollesello, S-E Ricksten, H Riha, A Rudiger, F Sangalli
Levosimendan is an inodilator that promotes cardiac contractility primarily via calcium sensitization of cardiac troponin C and vasodilatation via opening of adenosine triphosphate-sensitive potassium (KATP) channels in vascular smooth muscle cells; the drug also exerts organ-protective effects via a similar effect on mitochondrial KATP channels.This pharmacological profile identifies levosimendan as a drug that may have applications in a wide range of critical illness situations encountered in intensive care unit medicine: hemodynamic support in cardiogenic or septic shock; weaning from mechanical ventilation or from extracorporeal membrane oxygenation; and in the context of cardiorenal syndrome...
November 22, 2018: Journal of Cardiovascular Pharmacology
Xiaomeng Zhang, Beilei Wang, Zhenzhen Liu, Yubin Zhou, Lupei Du
hERG (Human ether-a-go-go-related gene) potassium channel, which plays an essential role in cardiac action potential repolarization, is responsible for inherited and drug-induced long QT syndrome. Recently, the Cryo-EM structure capturing the open conformation of hERG channel was determined, thus pushing the study on hERG channel at 3.8 Å resolution. This report focuses primarily on summarizing the design rationale and application of several fluorescent probes that target hERG channels, which enables dynamic and real-time monitoring of potassium pore channel affinity to further advance the understanding of the channels...
November 28, 2018: Current Medicinal Chemistry
Meng Han, Miao Zhao, Chen Cheng, Yuan Huang, Shengna Han, Wenjuan Li, Xin Tu, Xuan Luo, Xiaoling Yu, Yinan Liu, Qiuyun Chen, Xiang Ren, Qing Kenneth Wang, Tie Ke
Atrial fibrillation (AF) is the most common cardiac arrhythmia. Here we show the identification and functional characterization of one AF-associated mutation p.Arg399Cys in lamin A/C. Co-immunoprecipitation and GST pull-down assays demonstrate that lamin A/C interacts with NUP155, which is a nucleoporin and causes AF when mutated. Lamin A/C mutation p.Arg399Cys impairs the interaction between lamin A/C and NUP155, and increases extractability of NUP155 from the nuclear envelope (NE). Mutation p.Arg399Cys leads to aggregation of lamin A/C in the nucleus, although it does not impair the integrity of NE upon cellular stress...
November 29, 2018: Human Mutation
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