Pain-Enhancing Mechanism Through Interaction Between TRPV1 and Anoctamin 1 in Sensory Neurons
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Combined Pharmacological Administration of AQP1 Ion Channel
www.nature.com/scientificreports OPEN Combined pharmacological administration of AQP1 ion channel blocker AqB011 and water channel Received: 15 November 2018 Accepted: 13 August 2019 blocker Bacopaside II amplifes Published: xx xx xxxx inhibition of colon cancer cell migration Michael L. De Ieso 1, Jinxin V. Pei 1, Saeed Nourmohammadi1, Eric Smith 1,2, Pak Hin Chow1, Mohamad Kourghi1, Jennifer E. Hardingham 1,2 & Andrea J. Yool 1 Aquaporin-1 (AQP1) has been proposed as a dual water and cation channel that when upregulated in cancers enhances cell migration rates; however, the mechanism remains unknown. Previous work identifed AqB011 as an inhibitor of the gated human AQP1 cation conductance, and bacopaside II as a blocker of AQP1 water pores. In two colorectal adenocarcinoma cell lines, high levels of AQP1 transcript were confrmed in HT29, and low levels in SW480 cells, by quantitative PCR (polymerase chain reaction). Comparable diferences in membrane AQP1 protein levels were demonstrated by immunofuorescence imaging. Migration rates were quantifed using circular wound closure assays and live-cell tracking. AqB011 and bacopaside II, applied in combination, produced greater inhibitory efects on cell migration than did either agent alone. The high efcacy of AqB011 alone and in combination with bacopaside II in slowing HT29 cell motility correlated with abundant membrane localization of AQP1 protein. In SW480, neither agent alone was efective in blocking cell motility; however, combined application did cause inhibition of motility, consistent with low levels of membrane AQP1 expression. Bacopaside alone or combined with AqB011 also signifcantly impaired lamellipodial formation in both cell lines. Knockdown of AQP1 with siRNA (confrmed by quantitative PCR) reduced the efectiveness of the combined inhibitors, confrming AQP1 as a target of action. -
Action Potential and Synapses
SENSORY RECEPTORS RECEPTORS GATEWAY TO THE PERCEPTION AND SENSATION Registering of inputs, coding, integration and adequate response PROPERTIES OF THE SENSORY SYSTEM According the type of the stimulus: According to function: MECHANORECEPTORS Telereceptors CHEMORECEPTORS Exteroreceptors THERMORECEPTORS Proprioreceptors PHOTORECEPTORS interoreceptors NOCICEPTORS STIMULUS Reception Receptor – modified nerve or epithelial cell responsive to changes in external or internal environment with the ability to code these changes as electrical potentials Adequate stimulus – stimulus to which the receptor has lowest threshold – maximum sensitivity Transduction – transformation of the stimulus to membrane potential – to generator potential– to action potential Transmission – stimulus energies are transported to CNS in the form of action potentials Integration – sensory information is transported to CNS as frequency code (quantity of the stimulus, quantity of environmental changes) •Sensation is the awareness of changes in the internal and external environment •Perception is the conscious interpretation of those stimuli CLASSIFICATION OF RECEPTORS - adaptation NONADAPTING RECEPTORS WITH CONSTANT FIRING BY CONSTANT STIMULUS NONADAPTING – PAIN TONIC – SLOWLY ADAPTING With decrease of firing (AP frequency) by constant stimulus PHASIC– RAPIDLY ADAPTING With rapid decrease of firing (AP frequency) by constant stimulus ACCOMODATION – ADAPTATION CHARACTERISTICS OF PHASIC RECEPTORS ALTERATIONS OF THE MEMBRANE POTENTIAL ACTION POTENTIAL TRANSMEMBRANE POTENTIAL -
Ion Channels of Nociception
International Journal of Molecular Sciences Editorial Ion Channels of Nociception Rashid Giniatullin A.I. Virtanen Institute, University of Eastern Finland, 70211 Kuopio, Finland; Rashid.Giniatullin@uef.fi; Tel.: +358-403553665 Received: 13 May 2020; Accepted: 15 May 2020; Published: 18 May 2020 Abstract: The special issue “Ion Channels of Nociception” contains 13 articles published by 73 authors from different countries united by the main focusing on the peripheral mechanisms of pain. The content covers the mechanisms of neuropathic, inflammatory, and dental pain as well as pain in migraine and diabetes, nociceptive roles of P2X3, ASIC, Piezo and TRP channels, pain control through GPCRs and pharmacological agents and non-pharmacological treatment with electroacupuncture. Keywords: pain; nociception; sensory neurons; ion channels; P2X3; TRPV1; TRPA1; ASIC; Piezo channels; migraine; tooth pain Sensation of pain is one of the fundamental attributes of most species, including humans. Physiological (acute) pain protects our physical and mental health from harmful stimuli, whereas chronic and pathological pain are debilitating and contribute to the disease state. Despite active studies for decades, molecular mechanisms of pain—especially of pathological pain—remain largely unaddressed, as evidenced by the growing number of patients with chronic forms of pain. There are, however, some very promising advances emerging. A new field of pain treatment via neuromodulation is quickly growing, as well as novel mechanistic explanations unleashing the efficiency of traditional techniques of Chinese medicine. New molecular actors with important roles in pain mechanisms are being characterized, such as the mechanosensitive Piezo ion channels [1]. Pain signals are detected by specialized sensory neurons, emitting nerve impulses encoding pain in response to noxious stimuli. -
The Cys-Loop Ligand-Gated Ion Channel Gene Superfamily of the Parasitoid Wasp, Nasonia Vitripennis
Heredity (2010) 104, 247–259 & 2010 Macmillan Publishers Limited All rights reserved 0018-067X/10 $32.00 www.nature.com/hdy ORIGINAL ARTICLE The cys-loop ligand-gated ion channel gene superfamily of the parasitoid wasp, Nasonia vitripennis AK Jones, AN Bera, K Lees and DB Sattelle MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK Members of the cys-loop ligand-gated ion channel (cysLGIC) Nasonia possesses ion channels predicted to be gated superfamily mediate chemical neurotransmission and by acetylcholine, g-amino butyric acid, glutamate and are studied extensively as potential targets of drugs used histamine, as well as orthologues of the Drosophila to treat neurological disorders, such as Alzheimer’s disease. pH-sensitive chloride channel (pHCl), CG8916 and Insect cys-loop LGICs also have central roles in the nervous CG12344. Similar to other insects, wasp cysLGIC diversity system and are targets of highly successful insecticides. is broadened by alternative splicing and RNA A-to-I editing, Here, we describe the cysLGIC superfamily of the parasitoid which may also serve to generate species-specific recep- wasp, Nasonia vitripennis, which is emerging as a highly tor isoforms. These findings on N. vitripennis enhance useful model organism and is deployed as a biological our understanding of cysLGIC functional genomics and control of insect pests. The wasp superfamily consists of 26 provide a useful basis for the study of their function in the genes, which is the largest insect cysLGIC superfamily wasp model, as well as for the development of improved characterized, whereas Drosophila melanogaster, Apis insecticides that spare a major beneficial insect species. -
The Basic Hypothesis for Mechanotransduction in Sensory Receptors
Trakia Journal of Sciences, Vol. 17, Suppl. 2, pp 22-26, 2019 Copyright © 2019 Trakia University Available online at: http://www.uni-sz.bg ISSN 1313-3551 (online) doi:10.15547/tjs.2019.s.02.006 THE BASIC HYPOTHESIS FOR MECHANOTRANSDUCTION IN SENSORY RECEPTORS Ch. Chouchkov, Iv. Maslarski* Department of Anatomy, Histology, Pathology and Forensic Medicine, Faculty of Medicine, SU “St. Kliment Ohridski”, Sofia, Bulgaria ABSTRACT One of the most involving problem in the nerve tissue organization is the process of information transduction in the sеnsory receptors and the associated with them sensory cells. The aim of the present report is to review and discuss the data during the latter twenty years about the localization of molecules recently localized in different structural elements of sensory corpuscles and their possible role in the process of mechanotransduction. The most important obligatory parts in the process of mechanotransduction of all sensory receptors are their non-myelinated parts and their bulbous ends or so called nerve endings, like Pacinian and Meissner corpuscles, Krauses bulb, Golgi-Mazzoni corpuscle and Merkel disk. In conclusion, it is still a matter of elucidation in the future to precisely localize the proteins making up the mechanosensitive ion channels. There also exist difficulties regarding the correlation of the physiological with morphological data due to the fact that the receptor axolemma is surrounded by complex cellular structures whose isolation is hard to perform. Key words: Merkel disk, Pacinian corpuscle, Schwann inner core complex, neurotransmission INTRODUCTION mechanotransduction. The sensory receptors, One of the most intriguing problem in the responsible for the process of nerve tissue organization is the process of mechanotransduction are designed as information transduction in the sеnsory mechanoreceptors. -
The ATP-Releasing Maxi-Cl Channel: Its Identity, Molecular Partners, and Physiological/Pathophysiological Implications
life Review The ATP-Releasing Maxi-Cl Channel: Its Identity, Molecular Partners, and Physiological/Pathophysiological Implications Ravshan Z. Sabirov 1,2,*, Md. Rafiqul Islam 1,3, Toshiaki Okada 1,4, Petr G. Merzlyak 1,2 , Ranokhon S. Kurbannazarova 1,2, Nargiza A. Tsiferova 1,2 and Yasunobu Okada 1,5,6,* 1 Division of Cell Signaling, National Institute for Physiological Sciences (NIPS), Okazaki 444-8787, Japan; rafi[email protected] (M.R.I.); [email protected] (T.O.); [email protected] (P.G.M.); [email protected] (R.S.K.); [email protected] (N.A.T.) 2 Institute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent 100174, Uzbekistan 3 Department of Biochemistry and Molecular Biology, Jagannath University, Dhaka 1100, Bangladesh 4 Veneno Technologies Co. Ltd., Tsukuba 305-0031, Japan 5 Department of Physiology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan 6 Department of Physiology, School of Medicine, Aichi Medical University, Nagakute 480-1195, Japan * Correspondence: [email protected] (R.Z.S.); [email protected] (Y.O.); Tel.: +81-46-858-1501 (Y.O.); Fax: +81-46-858-1542 (Y.O.) Abstract: The Maxi-Cl phenotype accounts for the majority (app. 60%) of reports on the large- conductance maxi-anion channels (MACs) and has been detected in almost every type of cell, including placenta, endothelium, lymphocyte, cardiac myocyte, neuron, and glial cells, and in cells originating from humans to frogs. A unitary conductance of 300–400 pS, linear current-to- Citation: Sabirov, R.Z.; Islam, M..R.; voltage relationship, relatively high anion-to-cation selectivity, bell-shaped voltage dependency, Okada, T.; Merzlyak, P.G.; and sensitivity to extracellular gadolinium are biophysical and pharmacological hallmarks of the Kurbannazarova, R.S.; Tsiferova, Maxi-Cl channel. -
Beyond Water Homeostasis: Diverse Functional Roles of Mammalian Aquaporins Philip Kitchena, Rebecca E. Dayb, Mootaz M. Salmanb
CORE Metadata, citation and similar papers at core.ac.uk Provided by Aston Publications Explorer © 2015, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ Beyond water homeostasis: Diverse functional roles of mammalian aquaporins Philip Kitchena, Rebecca E. Dayb, Mootaz M. Salmanb, Matthew T. Connerb, Roslyn M. Billc and Alex C. Connerd* aMolecular Organisation and Assembly in Cells Doctoral Training Centre, University of Warwick, Coventry CV4 7AL, UK bBiomedical Research Centre, Sheffield Hallam University, Howard Street, Sheffield S1 1WB, UK cSchool of Life & Health Sciences and Aston Research Centre for Healthy Ageing, Aston University, Aston Triangle, Birmingham, B4 7ET, UK dInstitute of Clinical Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK * To whom correspondence should be addressed: Alex C. Conner, School of Clinical and Experimental Medicine, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. 0044 121 415 8809 ([email protected]) Keywords: aquaporin, solute transport, ion transport, membrane trafficking, cell volume regulation The abbreviations used are: GLP, glyceroporin; MD, molecular dynamics; SC, stratum corneum; ANP, atrial natriuretic peptide; NSCC, non-selective cation channel; RVD/RVI, regulatory volume decrease/increase; TM, transmembrane; ROS, reactive oxygen species 1 Abstract BACKGROUND: Aquaporin (AQP) water channels are best known as passive transporters of water that are vital for water homeostasis. SCOPE OF REVIEW: AQP knockout studies in whole animals and cultured cells, along with naturally occurring human mutations suggest that the transport of neutral solutes through AQPs has important physiological roles. Emerging biophysical evidence suggests that AQPs may also facilitate gas (CO2) and cation transport. -
Neurotransmission
Neurotransmission Prof. Dr. Szabolcs Kéri University of Szeged, Faculty of Medicine, Department of Physiology 2021 Why studying synapses? Synaptopathy: diseases of the brain characterized by pathological synaptic structure and function Key points 1. Synapsis: definition and classification 2. Signal transduction in the synapsis 3. Neurotransmitters: definition and classification 4. Important transmitter systems and their functions 5. Non-conventional transmission: axon – glial connection, retrograde signals, and volume transmission 1. Definition and classification of synapses Definition and classification of synapses Synapsis: Axons do not form a continuous network. They make contacts with dendrites or cell bodies. Synapse is a connection point to pass electrical or chemical signals to another neuron or to a target cell. A. CHEMICAL (neurotransmitter and receptor) B. ELECTRIC (gap junction) I. Connection type: II. Transmitter type and function: • Axodendritic • Excitatory (Gray I: asymmetric, glutamate, spherical • Axosomatic vesicles) • Axoaxonal • Inhibitory (Gray II: symmetric, GABA, oval vesicles) • Axomyelinic • Modulatory (monoamines, small dense core vesicles) • Peptides (large dense core vesicles) Spine Clear vesicles Spine synapse Dense core vesicles Shaft snapse Gray I Gray II Asymmetric Symmetric Glutamate GABA Axodendritic Axoaxonal Posztszinaptikus Axosomatic Postsynapticdenzitás (PSD)density (PSD) Outlook: molecular diversity of the synapses 2. Signal transduction in the synapse Electric synapses: comparison with chemical synapses ELECTRIC • Connexon pore (6 connexins) • Bidirectional diffusion of small molecules • Fast: minimal synaptic delay • Synchronization of neuronal groups • Glial networks • Passing second messengers (cAMP) CHEMICAL • No pore in the membrane (transmitter and receptor needed) • Synaptic delay (1-1.5 ms) • One-way (pre → postsynaptic) Chemical neurotransmission 1. Transmitter stored in vesicles 2. 2. Action potential at the presynaptic terminal 1. -
Inward-Rectifier Chloride Currents in Reissner's
INWARD-RECTIFIER CHLORIDE CURRENTS IN REISSNER’S MEMBRANE EPITHELIAL CELLS by KYUNGHEE KIM B.S., Sookmyung Women’s University, Seoul, South Korea 1999-2003 M.S., KAIST (Korea Advanced Institute of Science and Technology), Daejeon, South Korea 2003-2005 A THESIS submitted in partial fulfillment of the requirements for the degree MASTER OF SCIENCE Department of Anatomy and Physiology College of Veterinary Medicine KANSAS STATE UNIVERSITY Manhattan, Kansas 2010 Approved by: Major Professor Dr. Daniel C. Marcus Abstract Sensory transduction in the cochlea depends on regulated ion secretion and absorption. Results of whole-organ experiments suggested that Reissner’s membrane may play a role in the control of luminal Cl-. We tested for the presence of Cl- transport pathways in isolated mouse Reissner’s membrane using whole-cell patch clamp recordings and gene transcript analyses using RT-PCR. The current-voltage (I-V) relationship in the presence of symmetrical NMDG-Cl was strongly inward-rectifying at negative voltages, with a small outward current at positive voltages. The inward-rectifying component of the I-V curve had several properties similar to those of the ClC- 2 Cl- channel. It was stimulated by extracellular acidity and inhibited by extracellular Cd2+, Zn2+, and intracellular ClC-2 antibody. Channel transcripts expressed in Reissner’s membrane include ClC-2, Slc26a7 and ClC-Ka, but not Cftr, ClC-1, ClCa1, ClCa2, ClCa3, ClCa4, Slc26a9, ClC-Kb, Best1, Best2, Best3 or the beta-subunit of ClC-K, barttin. ClC-2 is the only molecularly-identified channel present that is a strong inward rectifier. This thesis incorporates the publication by KX Kim and DC Marcus, Inward-rectifier chloride currents in Reissner’s membrane epithelial cells, Biochem. -
Educational Research Applications Detwiler PB., Educ Res Appl: ERCA-138 Review Article DOI: 10.29011/2575-7032/100038 Sensory Transduction: a Common Blue Print
Educational Research Applications Detwiler PB., Educ Res Appl: ERCA-138 Review Article DOI: 10.29011/2575-7032/100038 Sensory Transduction: A Common Blue Print Peter B Detwiler Ph.D.* Department Physiology & Biophysics, School of Medicine, University of Washington, USA *Corresponding author: Peter B. Detwiler, Ph.D., Department Physiology & Biophysics, School of Medicine, University of Wash- ington, Seattle, WA 98195 USA. Tel: 1 (206) 543-0957; Email: [email protected] Citation: Detwiler PB (2017) Sensory Transduction: A Common Blue Print. Educ Res Appl: ERCA-138. DOI: 10.29011/2575- 7032/100038 Received Date: 17 October, 2017; Accepted Date: 30 October, 2017; Published Date: 07 November, 2017 Abstract Sensory receptors are transducers that convert a physical signal in the outside world into a cellular signal that can be inte- grated, transmitted, processed and interpreted by the nervous system. While the assortment of different types of sensory receptor is able to detect and selectively respond to a wide range of diverse extracellular signals they all work in basically the same way according to common blue print. They are compartmentalized input-output cells. For a specific signal to be detected it must first act on specialized membrane proteins (detector proteins) in the input or transduction region of the cell. This interaction generates a change in membrane voltage (receptor potential) by opening or closing ion channels either directly or indirectly via an enzyme cascade that controls the concentration of an intracellular second messenger (a cyclic nucleotide or calcium). The resulting electri- cal signal is communicated to the output region of the cell where it regulates Ca2+ dependent exocytosis of a chemical transmitter that carries the sensory signal to the next cell in the sensory pathway. -
Tutorial on Moa Mechanisms
Insecticide Mode of Action Training slide deck IRAC MoA Workgroup Version 1.0, April 2019 1 Details are accurate to the best of our knowledge but IRAC and its member companies cannot accept responsibility for how the information is used or interpreted. Protected by © Copyright What is an Insecticide’s ‘Mode of Action’? The Mode of action defines the process of how an insecticide works on an insect or mite at a molecular level Why is it good to know the Mode of Action of an Insecticide? Knowing the Mode of action of an insecticide is key to managing resistance The Insecticide Resistance Action Committee (IRAC) is a coordinated industry response to resistance management 2 Details are accurate to the best of our knowledge but IRAC and its member companies cannot accept responsibility for how the information is used or interpreted. Protected by © Copyright ADME is an important factor in an insecticide’s bioavailability n Absorption q Through the cuticle q Orally through consumption q Inhaled through spiracles as vapor n Distribution Metabolic q Through the body to target sites Enzymes n Metabolism (Break down) q By insect defense mechanisms n Excretion 3 Details are accurate to the best of our knowledge but IRAC and its member companies cannot accept responsibility for how the information is used or interpreted. Protected by © Copyright Insecticides act on key functional proteins that regulate vital processes Target protein e.g. ion channel binding pocket Small molecule insecticide Insecticides act on key functional proteins that regulate vital processes Altered protein function 1. A protein can have more than one binding pocket for small molecules Altered 2. -
Αcgrp Is Essential for Algesic Exocytotic Mobilization of TRPV1 Channels in Peptidergic Nociceptors
αCGRP is essential for algesic exocytotic mobilization of TRPV1 channels in peptidergic nociceptors Isabel Devesaa, Clotilde Ferrándiz-Huertasa, Sakthikumar Mathivanana, Christoph Wolfa, Rafael Lujánb, Jean-Pierre Changeuxc,d,1, and Antonio Ferrer-Montiela,e,1 aInstituto de Biología Molecular y Celular, Universidad Miguel Hernández, 03202 Elche, Spain; bDepartment Ciencias Médicas, Instituto de Investigación en Discapacidades Neurológicas, Facultad de Medicina, Universidad Castilla-La Mancha, 02006 Albacete, Spain; cCollège de France, 75005 Paris, France; dInstitut Pasteur, Centre National de la Recherche Scientifique, Unité de Recherche Associée, 7506 Paris, France; and eUnidad de Biofísica, Universidad del País Vasco/Euskal Herriko Unibertsitatea, Consejo Superior de Investigaciones Científicas, 48940 Leioa, Spain Contributed by Jean-Pierre Changeux, October 31, 2014 (sent for review August 12, 2014) Proalgesic sensitization of peripheral nociceptors in painful syn- LDCVs can also serve as carriers of a plethora of signaling dromes is a complex molecular process poorly understood that molecules, including ion channels and receptors that may enable involves mobilization of thermosensory receptors to the neuronal fast modulation of neuronal excitability (23). This finding raises surface. However, whether recruitment of vesicular thermoTRP the exciting hypothesis that proalgesic recruitment of TRPV1 channels is a general mechanism underlying sensitization of all channels is a mechanism occurring in peptidergic nociceptors. nociceptor types