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https://www.readbyqxmd.com/read/29205356/molecular-and-functional-characterization-of-inwardly-rectifying-k-currents-in-murine-proximal-colon
#1
Xu Huang, Si Hyung Lee, Hongli Lu, Kenton M Sanders, Sang Don Koh
Membrane potentials of gastrointestinal (GI) muscles are important because voltage dependent Ca2+ channels in smooth muscle cells (SMC) provide the Ca2+ that triggers contraction. Regulation of membrane potential is complicated because SMC are electrically coupled to interstitial cells of Cajal (ICC) and PDGFRα+ cells. Activation of conductances in any of these cells affects the excitability of the syncytium. We explored the role of inward rectifier K+ conductances in colonic ICC that might contribute to regulation of membrane potential...
December 3, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29055952/aloe-emodin-relieves-high-fat-diet-induced-qt-prolongation-via-mir-1-inhibition-and-ik1-up-regulation-in-rats
#2
Yan Bai, Zhenli Su, Hanqi Sun, Wei Zhao, Xue Chen, Pengzhou Hang, Wenliang Zhu, Zhimin Du
BACKGROUND/AIMS: High-fat diet (HFD) causes cardiac electrical remodeling and increases the risk of ventricular arrhythmias. Aloe-emodin (AE) is an anthraquinone component isolated from rhubarb and has a similar chemical structure with emodin. The protective effect of emodin against cardiac diseases has been reported in the literature. However, the cardioprotective property of AE is still unknown. The present study investigated the effect of AE on HFD-induced QT prolongation in rats. METHODS: Adult male Wistar rats were randomly divided into three groups: control, HFD, and AE-treatment groups...
October 20, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29020060/phosphatidylinositol-4-5-bisphosphate-is-required-for-kcnq1-kcne1-channel-function-but-not-anterograde-trafficking
#3
Alice A Royal, Andrew Tinker, Stephen C Harmer
The slow delayed-rectifier potassium current (IKs) is crucial for human cardiac action potential repolarization. The formation of IKs requires co-assembly of the KCNQ1 α-subunit and KCNE1 β-subunit, and mutations in either of these subunits can lead to hereditary long QT syndrome types 1 and 5, respectively. It is widely recognised that the KCNQ1/KCNE1 (Q1/E1) channel requires phosphatidylinositol-4,5-bisphosphate (PIP2) binding for function. We previously identified a cluster of basic residues in the proximal C-terminus of KCNQ1 that form a PIP2/phosphoinositide binding site...
2017: PloS One
https://www.readbyqxmd.com/read/29017447/characterization-of-a-novel-kcnj2-sequence-variant-detected-in-andersen-tawil-syndrome-patients
#4
Stefanie Scheiper, Brigitte Hertel, Britt-Maria Beckmann, Stefan Kääb, Gerhard Thiel, Silke Kauferstein
BACKGROUND: Mutations in the KCNJ2 gene encoding the ion channel Kir2.1 have been linked to the Andersen-Tawil syndrome (ATS). Molecular genetic screening performed in a family exhibiting clinical ATS phenotypes unmasked a novel sequence variant (c.434A > G, p.Y145C) in this gene. The aim of this study was to investigate the effect of this variant on Kir2.1 ion channel functionality. METHODS: Mutant as well as wild type GFP tagged Kir2.1 channels were expressed in HEK293 cells...
October 10, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28957802/overexpression-of-m3-muscarinic-receptor-suppressed-adverse-electrical-remodeling-in-hypertrophic-myocardium-via-increasing-repolarizing-k-currents
#5
Xue Chen, Yan Bai, Hanqi Sun, Zhenli Su, Jing Guo, Chuan Sun, Zhimin Du
BACKGROUND/AIMS: Cardiac hypertrophy (CH) is an adaptive response to diverse cardiovascular conditions, which is accompanied by adverse electrical remodeling manifested as abnormal K+ channel activities. M3 subtype of muscarinic acetylcholine receptor (M3-mAChR) is a novel regulator of cardiac electrical activity. In this study we aim to explore if the overexpression of M3-mAChR could attenuate the adverse electrical remodeling in CH and then uncover its underlying electrophysiological mechanisms...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28830445/responses-of-rat-and-mouse-primary-microglia-to-pro-and-anti-inflammatory-stimuli-molecular-profiles-k-channels-and-migration
#6
Doris Lam, Starlee Lively, Lyanne C Schlichter
BACKGROUND: Acute CNS damage is commonly studied using rat and mouse models, but increasingly, molecular analysis is finding species differences that might affect the ability to translate findings to humans. Microglia can undergo complex molecular and functional changes, often studied by in vitro responses to discrete activating stimuli. There is considerable evidence that pro-inflammatory (M1) activation can exacerbate tissue damage, while anti-inflammatory (M2) states help resolve inflammation and promote tissue repair...
August 22, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28711067/pa-6-inhibits-inward-rectifier-currents-carried-by-v93i-and-d172n-gain-of-function-kir2-1-channels-but-increases-channel-protein-expression
#7
Yuan Ji, Marlieke G Veldhuis, Jantien Zandvoort, Fee L Romunde, Marien J C Houtman, Karen Duran, Gijs van Haaften, Eva-Maria Zangerl-Plessl, Hiroki Takanari, Anna Stary-Weinzinger, Marcel A G van der Heyden
BACKGROUND: The inward rectifier potassium current IK1 contributes to a stable resting membrane potential and phase 3 repolarization of the cardiac action potential. KCNJ2 gain-of-function mutations V93I and D172N associate with increased IK1, short QT syndrome type 3 and congenital atrial fibrillation. Pentamidine-Analogue 6 (PA-6) is an efficient (IC50 = 14 nM with inside-out patch clamp methodology) and specific IK1 inhibitor that interacts with the cytoplasmic pore region of the KIR2...
July 15, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28660286/hydrocinnamic-acid-inhibits-the-currents-of-wt-and-sqt3-syndrome-related-mutants-of-kir2-1-channel
#8
Shuxi Ren, Chunli Pang, Yayue Huang, Chengfen Xing, Yong Zhan, Hailong An
Gain of function in mutations, D172N and E299V, of Kir2.1 will induce type III short QT syndrome. In our previous work, we had identified that a mixture of traditional Chinese medicine, styrax, is a blocker of Kir2.1. Here, we determined a monomer, hydrocinnamic acid (HA), as the effective component from 18 compounds of styrax. Our data show that HA can inhibit the currents of Kir2.1 channel in both excised inside-out and whole-cell patch with the IC50 of 5.21 ± 1.02 and 10.08 ± 0.46 mM, respectively...
October 2017: Journal of Membrane Biology
https://www.readbyqxmd.com/read/28408648/azithromycin-causes-a-novel-proarrhythmic-syndrome
#9
Zhenjiang Yang, Joseph K Prinsen, Kevin R Bersell, Wangzhen Shen, Liudmila Yermalitskaya, Tatiana Sidorova, Paula B Luis, Lynn Hall, Wei Zhang, Liping Du, Ginger Milne, Patrick Tucker, Alfred L George, Courtney M Campbell, Robert A Pickett, Christian M Shaffer, Nagesh Chopra, Tao Yang, Bjorn C Knollmann, Dan M Roden, Katherine T Murray
BACKGROUND: The widely used macrolide antibiotic azithromycin increases risk of cardiovascular and sudden cardiac death, although the underlying mechanisms are unclear. Case reports, including the one we document here, demonstrate that azithromycin can cause rapid, polymorphic ventricular tachycardia in the absence of QT prolongation, indicating a novel proarrhythmic syndrome. We investigated the electrophysiological effects of azithromycin in vivo and in vitro using mice, cardiomyocytes, and human ion channels heterologously expressed in human embryonic kidney (HEK 293) and Chinese hamster ovary (CHO) cells...
April 2017: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/28389584/control-of-kir-channel-gating-by-cytoplasmic-domain-interface-interactions
#10
William F Borschel, Shizhen Wang, Sunjoo Lee, Colin G Nichols
Inward rectifier potassium (Kir) channels are expressed in almost all mammalian tissues and play critical roles in the control of excitability. Pancreatic ATP-sensitive K (KATP) channels are key regulators of insulin secretion and comprise Kir6.2 subunits coupled to sulfonylurea receptors. Because these channels are reversibly inhibited by cytoplasmic ATP, they link cellular metabolism with membrane excitability. Loss-of-function mutations in the pore-forming Kir6.2 subunit cause congenital hyperinsulinism as a result of diminished channel activity...
May 1, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28383527/activation-of-the-hypoglossal-to-tongue-musculature-motor-pathway-by-remote-control
#11
Garret A Horton, Jimmy J Fraigne, Zoltan A Torontali, Matthew B Snow, Jennifer L Lapierre, Hattie Liu, Gaspard Montandon, John H Peever, Richard L Horner
Reduced tongue muscle tone precipitates obstructive sleep apnea (OSA), and activation of the tongue musculature can lessen OSA. The hypoglossal motor nucleus (HMN) innervates the tongue muscles but there is no pharmacological agent currently able to selectively manipulate a channel (e.g., Kir2.4) that is highly restricted in its expression to cranial motor pools such as the HMN. To model the effect of manipulating such a restricted target, we introduced a "designer" receptor into the HMN and selectively modulated it with a "designer" drug...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28365825/inhibition-of-inwardly-rectifying-kir2-x-channels-by-the-novel-anti-cancer-agent-gambogic-acid-depends-on-both-pore-block-and-pip2-interference
#12
Daniel Scherer, Benedikt Schworm, Claudia Seyler, Panagiotis Xynogalos, Eberhard P Scholz, Dierk Thomas, Hugo A Katus, Edgar Zitron
The caged xanthone gambogic acid (GA) is a novel anti-cancer agent which exhibits anti-proliferative, anti-inflammatory and cytotoxic effects in many types of cancer tissues. In a recent phase IIa study, GA exhibits a favourable safety profile. However, limited data are available concerning its interaction with cardiac ion channels. Heteromeric assembly of Kir2.x channels underlies the cardiac inwardly rectifying IK1 current which is responsible for the stabilization of the diastolic resting membrane potential...
July 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28345117/inwardly-rectifying-k-currents-in-cultured-oligodendrocytes-from-rat-optic-nerve-are-insensitive-to-ph
#13
Alberto Pérez-Samartín, Edith Garay, Juan Pablo H Moctezuma, Abraham Cisneros-Mejorado, María Victoria Sánchez-Gómez, Guadalupe Martel-Gallegos, Leticia Robles-Martínez, Manuel Canedo-Antelo, Carlos Matute, Rogelio O Arellano
Inwardly rectifying K(+) (Kir) channel expression signals at an advanced stage of maturation during oligodendroglial differentiation. Knocking down their expression halts the generation of myelin and produces severe abnormalities in the central nervous system. Kir4.1 is the main subunit involved in the tetrameric structure of Kir channels in glial cells; however, the precise composition of Kir channels expressed in oligodendrocytes (OLs) remains partially unknown, as participation of other subunits has been proposed...
September 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28301408/k-cl-cotransporter-2-mediated-cl-extrusion-determines-developmental-stage-dependent-impact-of-propofol-anesthesia-on-dendritic-spines
#14
Martin Puskarjov, Hubert Fiumelli, Adrian Briner, Timea Bodogan, Kornel Demeter, Claudia-Marvine Lacoh, Martina Mavrovic, Peter Blaesse, Kai Kaila, Laszlo Vutskits
BACKGROUND: General anesthetics potentiating γ-aminobutyric acid (GABA)-mediated signaling are known to induce a persistent decrement in excitatory synapse number in the cerebral cortex when applied during early postnatal development, while an opposite action is produced at later stages. Here, the authors test the hypothesis that the effect of general anesthetics on synaptogenesis depends upon the efficacy of GABA receptor type A (GABAA)-mediated inhibition controlled by the developmental up-regulation of the potassium-chloride (K-Cl) cotransporter 2 (KCC2)...
May 2017: Anesthesiology
https://www.readbyqxmd.com/read/28289282/the-schizophrenia-and-autism-associated-gene-transcription-factor-4-regulates-the-columnar-distribution-of-layer-2-3-prefrontal-pyramidal-neurons-in-an-activity-dependent-manner
#15
S C Page, G R Hamersky, R A Gallo, M D Rannals, N E Calcaterra, M N Campbell, B Mayfield, A Briley, B N Phan, A E Jaffe, B J Maher
Disruption of the laminar and columnar organization of the brain is implicated in several psychiatric disorders. Here, we show in utero gain-of-function of the psychiatric risk gene transcription factor 4 (TCF4) severely disrupts the columnar organization of medial prefrontal cortex (mPFC) in a transcription- and activity-dependent manner. This morphological phenotype was rescued by co-expression of TCF4 plus calmodulin in a calcium-dependent manner and by dampening neuronal excitability through co-expression of an inwardly rectifying potassium channel (Kir2...
March 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28284503/renal-denervation-regulates-the-atrial-arrhythmogenic-substrates-through-reverse-structural-remodeling-in-heart-failure-rabbit-model
#16
Shinya Yamada, Li-Wei Lo, Yu-Hui Chou, Wei-Lun Lin, Shih-Lin Chang, Yenn-Jiang Lin, Shih-Ann Chen
BACKGROUND: Heart failure (HF) causes atrial remodeling and increases the incidence of atrial fibrillation (AF). Renal denervation (RDN) has been shown to decrease the development of AF. This study aimed to identify the effects of RDN on the atrial arrhythmogenic substrates in HF. METHODS: Rabbits were classified into four groups: control (n=9), RDN (n=10), HF (n=6) and HF-RDN (n=9). Surgical and chemical RDN was approached through bilateral retroperitoneal flank incisions in RDN and HF-RDN...
May 15, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28148533/inhibition-of-vascular-smooth-muscle-inward-rectifier-k-channels-restores-myogenic-tone-in-mouse-urinary-bladder-arterioles
#17
Nathan R Tykocki, Adrian D Bonev, Thomas A Longden, Thomas J Heppner, Mark T Nelson
Prolonged decreases in urinary bladder blood flow are linked to overactive and underactive bladder pathologies. However, the mechanisms regulating bladder vascular reactivity are largely unknown. To investigate these mechanisms, we examined myogenic and vasoactive properties of mouse bladder feed arterioles (BFAs). Unlike similar-sized arterioles from other vascular beds, BFAs failed to constrict in response to increases in intraluminal pressure (5-80 mmHg). Consistent with this lack of myogenic tone, arteriolar smooth muscle cell membrane potential was hyperpolarized (-72...
May 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28112313/soluble-epoxide-hydrolase-inhibitors-might-prevent-ischemic-arrhythmias-via-microrna-1-repression-in-primary-neonatal-mouse-ventricular-myocytes
#18
Qiong Liu, Xuan Zhao, Ran Peng, Mi Wang, Wang Zhao, Ya-Jun Gui, Cai-Xiu Liao, Dan-Yan Xu
Ischemic arrhythmias are the main causes of sudden cardiac death. It has been reported that soluble epoxide hydrolase inhibitors (sEHis) could prevent arrhythmias; however, the underlying molecular mechanisms remain unclear. In recent years, the proarrhythmic role of microRNA-1 (miR-1) has been investigated. This study aimed to elucidate whether sEHis prevented ischemic arrhythmias by suppressing miR-1. The primary neonatal mouse ventricular myocyte model of miR-1 overexpression was established by incubating with agonist microONTM mmu-miR-1a-3p agomir (DAEDstain(TM) Dye) (agomiR-1)...
February 28, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28007664/effects-of-seasonal-acclimatization-on-action-potentials-and-sarcolemmal-k-currents-in-roach-rutilus-rutilus-cardiac-myocytes
#19
Ahmed Badr, Minna Hassinen, Mohamed F El-Sayed, Matti Vornanen
Temperature sensitivity of electrical excitability is a potential limiting factor for high temperature tolerance of ectotherms. The present study examines whether heat resistance of electrical excitability of cardiac myocytes is modified by seasonal thermal acclimatization in roach (Rutilus rutilus), a eurythermal teleost species. To this end, temperature dependencies of ventricular action potentials (APs), and atrial and ventricular K(+) currents were measured from winter-acclimatized (WiR) and summer-acclimatized (SuR) roach...
March 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/27882143/expression-of-connexin-43-ion-channels-and-ca-2-handling-proteins-in-rat-pulmonary-vein-cardiomyocytes
#20
Yaqiong Xiao, Xue Cai, Andrew Atkinson, Sunil Jit Logantha, Mark Boyett, Halina Dobrzynski
Atrial fibrillation (AF) is the most common cardiac arrhythmia. AF is thought to be triggered by ectopic beats, originating primarily in the myocardial sleeves surrounding the pulmonary veins (PVs). The mechanisms underlying these cardiac arrhythmias remain unclear. To investigate this, frozen sections of heart and lung tissue from adult rats without arrhythmia were obtained in different planes, stained with Masson's trichrome, and immunolabeled for connexin 43 (Cx43), caveolin-3 (Cav3), hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4), Nav1...
November 2016: Experimental and Therapeutic Medicine
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