IDENTIFICATION and CHARACTERIZATION of ALTERNATIVE SPLICE VARIANTS of the MOUSE Trek2/Kcnk10 GENE
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Potassium Channels in Epilepsy
Downloaded from http://perspectivesinmedicine.cshlp.org/ on September 28, 2021 - Published by Cold Spring Harbor Laboratory Press Potassium Channels in Epilepsy Ru¨diger Ko¨hling and Jakob Wolfart Oscar Langendorff Institute of Physiology, University of Rostock, Rostock 18057, Germany Correspondence: [email protected] This review attempts to give a concise and up-to-date overview on the role of potassium channels in epilepsies. Their role can be defined from a genetic perspective, focusing on variants and de novo mutations identified in genetic studies or animal models with targeted, specific mutations in genes coding for a member of the large potassium channel family. In these genetic studies, a demonstrated functional link to hyperexcitability often remains elusive. However, their role can also be defined from a functional perspective, based on dy- namic, aggravating, or adaptive transcriptional and posttranslational alterations. In these cases, it often remains elusive whether the alteration is causal or merely incidental. With 80 potassium channel types, of which 10% are known to be associated with epilepsies (in humans) or a seizure phenotype (in animals), if genetically mutated, a comprehensive review is a challenging endeavor. This goal may seem all the more ambitious once the data on posttranslational alterations, found both in human tissue from epilepsy patients and in chronic or acute animal models, are included. We therefore summarize the literature, and expand only on key findings, particularly regarding functional alterations found in patient brain tissue and chronic animal models. INTRODUCTION TO POTASSIUM evolutionary appearance of voltage-gated so- CHANNELS dium (Nav)andcalcium (Cav)channels, Kchan- nels are further diversified in relation to their otassium (K) channels are related to epilepsy newer function, namely, keeping neuronal exci- Psyndromes on many different levels, ranging tation within limits (Anderson and Greenberg from direct control of neuronal excitability and 2001; Hille 2001). -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
Transcriptomic Analysis of Native Versus Cultured Human and Mouse Dorsal Root Ganglia Focused on Pharmacological Targets Short
bioRxiv preprint doi: https://doi.org/10.1101/766865; this version posted September 12, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-ND 4.0 International license. Transcriptomic analysis of native versus cultured human and mouse dorsal root ganglia focused on pharmacological targets Short title: Comparative transcriptomics of acutely dissected versus cultured DRGs Andi Wangzhou1, Lisa A. McIlvried2, Candler Paige1, Paulino Barragan-Iglesias1, Carolyn A. Guzman1, Gregory Dussor1, Pradipta R. Ray1,#, Robert W. Gereau IV2, # and Theodore J. Price1, # 1The University of Texas at Dallas, School of Behavioral and Brain Sciences and Center for Advanced Pain Studies, 800 W Campbell Rd. Richardson, TX, 75080, USA 2Washington University Pain Center and Department of Anesthesiology, Washington University School of Medicine # corresponding authors [email protected], [email protected] and [email protected] Funding: NIH grants T32DA007261 (LM); NS065926 and NS102161 (TJP); NS106953 and NS042595 (RWG). The authors declare no conflicts of interest Author Contributions Conceived of the Project: PRR, RWG IV and TJP Performed Experiments: AW, LAM, CP, PB-I Supervised Experiments: GD, RWG IV, TJP Analyzed Data: AW, LAM, CP, CAG, PRR Supervised Bioinformatics Analysis: PRR Drew Figures: AW, PRR Wrote and Edited Manuscript: AW, LAM, CP, GD, PRR, RWG IV, TJP All authors approved the final version of the manuscript. 1 bioRxiv preprint doi: https://doi.org/10.1101/766865; this version posted September 12, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. -
Ion Channels 3 1
r r r Cell Signalling Biology Michael J. Berridge Module 3 Ion Channels 3 1 Module 3 Ion Channels Synopsis Ion channels have two main signalling functions: either they can generate second messengers or they can function as effectors by responding to such messengers. Their role in signal generation is mainly centred on the Ca2 + signalling pathway, which has a large number of Ca2+ entry channels and internal Ca2+ release channels, both of which contribute to the generation of Ca2 + signals. Ion channels are also important effectors in that they mediate the action of different intracellular signalling pathways. There are a large number of K+ channels and many of these function in different + aspects of cell signalling. The voltage-dependent K (KV) channels regulate membrane potential and + excitability. The inward rectifier K (Kir) channel family has a number of important groups of channels + + such as the G protein-gated inward rectifier K (GIRK) channels and the ATP-sensitive K (KATP) + + channels. The two-pore domain K (K2P) channels are responsible for the large background K current. Some of the actions of Ca2 + are carried out by Ca2+-sensitive K+ channels and Ca2+-sensitive Cl − channels. The latter are members of a large group of chloride channels and transporters with multiple functions. There is a large family of ATP-binding cassette (ABC) transporters some of which have a signalling role in that they extrude signalling components from the cell. One of the ABC transporters is the cystic − − fibrosis transmembrane conductance regulator (CFTR) that conducts anions (Cl and HCO3 )and contributes to the osmotic gradient for the parallel flow of water in various transporting epithelia. -
Ion Channels
UC Davis UC Davis Previously Published Works Title THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Ion channels. Permalink https://escholarship.org/uc/item/1442g5hg Journal British journal of pharmacology, 176 Suppl 1(S1) ISSN 0007-1188 Authors Alexander, Stephen PH Mathie, Alistair Peters, John A et al. Publication Date 2019-12-01 DOI 10.1111/bph.14749 License https://creativecommons.org/licenses/by/4.0/ 4.0 Peer reviewed eScholarship.org Powered by the California Digital Library University of California S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2019/20: Ion channels. British Journal of Pharmacology (2019) 176, S142–S228 THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Ion channels Stephen PH Alexander1 , Alistair Mathie2 ,JohnAPeters3 , Emma L Veale2 , Jörg Striessnig4 , Eamonn Kelly5, Jane F Armstrong6 , Elena Faccenda6 ,SimonDHarding6 ,AdamJPawson6 , Joanna L Sharman6 , Christopher Southan6 , Jamie A Davies6 and CGTP Collaborators 1School of Life Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK 2Medway School of Pharmacy, The Universities of Greenwich and Kent at Medway, Anson Building, Central Avenue, Chatham Maritime, Chatham, Kent, ME4 4TB, UK 3Neuroscience Division, Medical Education Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK 4Pharmacology and Toxicology, Institute of Pharmacy, University of Innsbruck, A-6020 Innsbruck, Austria 5School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, BS8 1TD, UK 6Centre for Discovery Brain Science, University of Edinburgh, Edinburgh, EH8 9XD, UK Abstract The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. -
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Supplemental Information Biological and Pharmaceutical Bulletin Promoter Methylation Profiles between Human Lung Adenocarcinoma Multidrug Resistant A549/Cisplatin (A549/DDP) Cells and Its Progenitor A549 Cells Ruiling Guo, Guoming Wu, Haidong Li, Pin Qian, Juan Han, Feng Pan, Wenbi Li, Jin Li, and Fuyun Ji © 2013 The Pharmaceutical Society of Japan Table S1. Gene categories involved in biological functions with hypomethylated promoter identified by MeDIP-ChIP analysis in lung adenocarcinoma MDR A549/DDP cells compared with its progenitor A549 cells Different biological Genes functions transcription factor MYOD1, CDX2, HMX1, THRB, ARNT2, ZNF639, HOXD13, RORA, FOXO3, HOXD10, CITED1, GATA1, activity HOXC6, ZGPAT, HOXC8, ATOH1, FLI1, GATA5, HOXC4, HOXC5, PHTF1, RARB, MYST2, RARG, SIX3, FOXN1, ZHX3, HMG20A, SIX4, NR0B1, SIX6, TRERF1, DDIT3, ASCL1, MSX1, HIF1A, BAZ1B, MLLT10, FOXG1, DPRX, SHOX, ST18, CCRN4L, TFE3, ZNF131, SOX5, TFEB, MYEF2, VENTX, MYBL2, SOX8, ARNT, VDR, DBX2, FOXQ1, MEIS3, HOXA6, LHX2, NKX2-1, TFDP3, LHX6, EWSR1, KLF5, SMAD7, MAFB, SMAD5, NEUROG1, NR4A1, NEUROG3, GSC2, EN2, ESX1, SMAD1, KLF15, ZSCAN1, VAV1, GAS7, USF2, MSL3, SHOX2, DLX2, ZNF215, HOXB2, LASS3, HOXB5, ETS2, LASS2, DLX5, TCF12, BACH2, ZNF18, TBX21, E2F8, PRRX1, ZNF154, CTCF, PAX3, PRRX2, CBFA2T2, FEV, FOS, BARX1, PCGF2, SOX15, NFIL3, RBPJL, FOSL1, ALX1, EGR3, SOX14, FOXJ1, ZNF92, OTX1, ESR1, ZNF142, FOSB, MIXL1, PURA, ZFP37, ZBTB25, ZNF135, HOXC13, KCNH8, ZNF483, IRX4, ZNF367, NFIX, NFYB, ZBTB16, TCF7L1, HIC1, TSC22D1, TSC22D2, REXO4, POU3F2, MYOG, NFATC2, ENO1, -
Electrophysiological Characterization of Ipsc-Derived Cortical Neurons Using Automated Patch Clamp Kadla R
Electrophysiological Characterization of iPSC-derived Cortical Neurons Using Automated Patch Clamp Kadla R. Rosholm1, Ivy Pin-Fang Chen3, Daniel R. Sauter2, Anders Lindqvist1, Taylor E. Forman3, Sean A. Dwyer3, Cindy Yang3, Elizabeth D. Buttermore3 1. Sophion Bioscience A/S, Baltorpvej 154, 2750 Ballerup – Denmark 2. Sophion Bisocience Inc., 400 Trade Center Drive, Suite 6900, Woburn, MA 01801 – United States 3. Human Neuron Core, Translational Neuroscience Center, Boston Children’s Hospital, Boston, MA – United States Introduction Imaging Automated patch clamp Ion channel analysis Electrophysiological comparison of CDKL5 proband and control iPSC neurons: Control neurons reveal the presence of Tuj1-positive and MAP2-positive cells with short neurites Experiment setup: Human induced pluripotent stem cells (hiPSCs) can be differentiated NaV analysis The measurements were fi ltered to include only neurons expressing both voltage-gated NaV and KV channels, which is a sign 24 hours after plating. CDKL5 proband neurons reveal more immature morphology, with large hiPSC derived cell lines are expensive and it is therefore of interest to limit cell con- into many cell types, including neurons and cardiomyocytes, and In agreement with literature, biophysical evaluation of the NaV currents indicate that only of maturity. The membrane resistance (Rmem), cell capacitance (Ccell) and resting membrane potential (RMP) were compared neural rosettes still present and Tuj1-positive neurons just beginning to emerge from the rosettes. sumption as much as possible. For that reason, we used a cell transfer plate (CTP), which therefore constitute a novel way to model human diseases1. However, tetrodotoxin (TTX)-sensitive NaV channels (i.e. NaV1.1, NaV1.2, NaV1.6) are present in the between the proband and isogenic control. -
1 1 2 3 Cell Type-Specific Transcriptomics of Hypothalamic
1 2 3 4 Cell type-specific transcriptomics of hypothalamic energy-sensing neuron responses to 5 weight-loss 6 7 Fredrick E. Henry1,†, Ken Sugino1,†, Adam Tozer2, Tiago Branco2, Scott M. Sternson1,* 8 9 1Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 10 20147, USA. 11 2Division of Neurobiology, Medical Research Council Laboratory of Molecular Biology, 12 Cambridge CB2 0QH, UK 13 14 †Co-first author 15 *Correspondence to: [email protected] 16 Phone: 571-209-4103 17 18 Authors have no competing interests 19 1 20 Abstract 21 Molecular and cellular processes in neurons are critical for sensing and responding to energy 22 deficit states, such as during weight-loss. AGRP neurons are a key hypothalamic population 23 that is activated during energy deficit and increases appetite and weight-gain. Cell type-specific 24 transcriptomics can be used to identify pathways that counteract weight-loss, and here we 25 report high-quality gene expression profiles of AGRP neurons from well-fed and food-deprived 26 young adult mice. For comparison, we also analyzed POMC neurons, an intermingled 27 population that suppresses appetite and body weight. We find that AGRP neurons are 28 considerably more sensitive to energy deficit than POMC neurons. Furthermore, we identify cell 29 type-specific pathways involving endoplasmic reticulum-stress, circadian signaling, ion 30 channels, neuropeptides, and receptors. Combined with methods to validate and manipulate 31 these pathways, this resource greatly expands molecular insight into neuronal regulation of 32 body weight, and may be useful for devising therapeutic strategies for obesity and eating 33 disorders. -
KCNK10, a Tandem Pore Domain Potassium Channel, Is a Regulator of Mitotic Clonal Expansion During the Early Stage of Adipocyte Differentiation
Int. J. Mol. Sci. 2014, 15, 22743-22756; doi:10.3390/ijms151222743 OPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 www.mdpi.com/journal/ijms Article KCNK10, a Tandem Pore Domain Potassium Channel, Is a Regulator of Mitotic Clonal Expansion during the Early Stage of Adipocyte Differentiation Makoto Nishizuka, Takahiro Hayashi, Mami Asano, Shigehiro Osada and Masayoshi Imagawa * Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan; E-Mails: [email protected] (M.N.); [email protected] (T.H.); [email protected] (M.A.); [email protected] (S.O.) * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +81-52-836-3455; Fax: +81-52-836-3765. External Editor: Julian Borejdo Received: 10 September 2014; in revised form: 10 November 2014 / Accepted: 26 November 2014 / Published: 9 December 2014 Abstract: KCNK10, a member of tandem pore domain potassium channel family, gives rise to leak K+ currents. It plays important roles in stabilizing the negative resting membrane potential and in counterbalancing depolarization. We previously demonstrated that kcnk10 expression is quickly elevated during the early stage of adipogenesis of 3T3-L1 cells and that reduction of kcnk10 expression inhibits adipocyte differentiation. However, the molecular mechanism of KCNK10 in adipocyte differentiation remains unclear. Here we revealed that kcnk10 is induced by 3-isobutyl-1-methylxanthine, a cyclic nucleotide phosphodiesterase inhibitor and a potent inducer of adipogenesis, during the early stage of adipocyte differentiation. -
GENE LIST ANTI-CORRELATED Systematic Common Description
GENE LIST ANTI-CORRELATED Systematic Common Description 210348_at 4-Sep Septin 4 206155_at ABCC2 ATP-binding cassette, sub-family C (CFTR/MRP), member 2 221226_s_at ACCN4 Amiloride-sensitive cation channel 4, pituitary 207427_at ACR Acrosin 214957_at ACTL8 Actin-like 8 207422_at ADAM20 A disintegrin and metalloproteinase domain 20 216998_s_at ADAM5 synonym: tMDCII; Homo sapiens a disintegrin and metalloproteinase domain 5 (ADAM5) on chromosome 8. 216743_at ADCY6 Adenylate cyclase 6 206807_s_at ADD2 Adducin 2 (beta) 208544_at ADRA2B Adrenergic, alpha-2B-, receptor 38447_at ADRBK1 Adrenergic, beta, receptor kinase 1 219977_at AIPL1 211560_s_at ALAS2 Aminolevulinate, delta-, synthase 2 (sideroblastic/hypochromic anemia) 211004_s_at ALDH3B1 Aldehyde dehydrogenase 3 family, member B1 204705_x_at ALDOB Aldolase B, fructose-bisphosphate 220365_at ALLC Allantoicase 204664_at ALPP Alkaline phosphatase, placental (Regan isozyme) 216377_x_at ALPPL2 Alkaline phosphatase, placental-like 2 221114_at AMBN Ameloblastin, enamel matrix protein 206892_at AMHR2 Anti-Mullerian hormone receptor, type II 217293_at ANGPT1 Angiopoietin 1 210952_at AP4S1 Adaptor-related protein complex 4, sigma 1 subunit 207158_at APOBEC1 Apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 213611_at AQP5 Aquaporin 5 216219_at AQP6 Aquaporin 6, kidney specific 206784_at AQP8 Aquaporin 8 214490_at ARSF Arylsulfatase F 216204_at ARVCF Armadillo repeat gene deletes in velocardiofacial syndrome 214070_s_at ATP10B ATPase, Class V, type 10B 221240_s_at B3GNT4 UDP-GlcNAc:betaGal -
(TREK2) Two-Pore-Domain K+ Channels
Biochimica et Biophysica Acta 1818 (2012) 33–41 Contents lists available at SciVerse ScienceDirect Biochimica et Biophysica Acta journal homepage: www.elsevier.com/locate/bbamem Identification and functional characterization of zebrafish K2P10.1 (TREK2) two-pore-domain K+ channels Jakob Gierten, David Hassel, Patrick A. Schweizer, Rüdiger Becker, Hugo A. Katus, Dierk Thomas ⁎ Department of Cardiology, Medical University Hospital Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany article info abstract + Article history: Two-pore-domain potassium (K2P) channels mediate K background currents that stabilize the resting Received 29 June 2011 membrane potential and contribute to repolarization of action potentials in excitable cells. The functional sig- Received in revised form 9 September 2011 nificance of K2P currents in cardiac electrophysiology remains poorly understood. Danio rerio (zebrafish) may Accepted 13 September 2011 be utilized to elucidate the role of cardiac K channels in vivo. The aim of this work was to identify and func- Available online 22 September 2011 2P tionally characterize a zebrafish otholog of the human K2P10.1 channel. K2P10.1 orthologs in the D. rerio ge- nome were identified by database analysis, and the full zK 10.1 coding sequence was amplified from Keywords: 2P fi fi Electrophysiology zebra sh cDNA. Human and zebra sh K2P10.1 proteins share 61% identity. High degrees of conservation Ion channel were observed in protein domains relevant for structural integrity and regulation. K2P10.1 channels were K+ leak current heterologously expressed in Xenopus oocytes, and currents were recorded using two-electrode voltage + K2P10.1 (TREK2) clamp electrophysiology. Human and zebrafish channels mediated K selective background currents lead- Membrane potential ing to membrane hyperpolarization. -
Viewed Papers: Yin K, Baillie GJ and Vetter I
A Pharmacological and Transcriptomic approach to exploring Novel Pain Targets Kathleen Yin Bachelor of Pharmacy A thesis submitted for the degree of Doctor of Philosophy at The University of Queensland in 2016 Institute for Molecular Bioscience i Abstract Ever since the discovery that mutations in the voltage-gated sodium channel 1.7 protein are responsible for human congenital insensitivity to pain, the voltage-gated sodium channel (NaV) family of ion channels has been the subject of intense research with the hope of discovering novel analgesics. We now know that NaV1.7 deletion in select neuronal populations yield different phenotypes, with the deletion of NaV1.7 in all sensory neurons being successful at abolishing mechanical and heat-induced pain. However, it is rapidly becoming apparent that a number of pain syndromes are not modulated by NaV1.7 at all, such as oxaliplatin-mediated neuropathy. It is particularly interesting to note that the loss of NaV1.7 function is also associated with the selective inhibition of pain mediated by specific stimuli, such as that observed in burn-induced pain where NaV1.7 gene knockout abolished thermal allodynia but did not affect mechanical allodynia. Accordingly, significant interests exist in delineating the contribution of other NaV isoforms in modality-specific pain pathways. Two other isoforms, NaV1.6 and NaV1.8, are now specifically implicated in some NaV1.7-independent conditions such as oxaliplatin-induced cold allodynia. Such selective contributions of specific ion channel isoforms to pain highlight the need to discover other putative protein targets involved in mediating nociception. The aim of my work is therefore to discover selective molecular inhibitors of NaV1.6 and NaV1.8, to find useful cell models for peripheral nociceptors, to investigate the roles of NaV1.6 and NaV1.8 in an animal model of burn-induced pain, and to screen for putative new targets for analgesia in burn-related pain.