DOCSLIB.ORG

The Transient Receptor Potential A1 Ion Channel (TRPA1) Modifies in Vivo Autonomous Ureter Peristalsis in Rats

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Transient Receptor Potential A1 Ion Channel (TRPA1) Modifies in Vivo Autonomous Ureter Peristalsis in Rats Received: 7 September 2020 | Revised: 23 October 2020 | Accepted: 5 November 2020 DOI: 10.1002/nau.24579 ORIGINAL BASIC SCIENCE ARTICLE The transient receptor potential A1 ion channel (TRPA1) modifies in vivo autonomous ureter peristalsis in rats Philipp Weinhold1 | Luca Villa2 | Frank Strittmatter1 | Christian Gratzke3 | Christian G. Stief1 | Fabio Castiglione4,5 | Francesco Montorsi2 | Petter Hedlund6,7 1Department of Urology, Ludwig‐ Maximilians‐University, Munich, Abstract Germany Aims: The current study aimed to explore the expression of transient receptor 2 Department of Urology, San Rafaele potential A1 ion channels (TRPA1) in the rat ureter and to assess if TRPA1‐active University, Milan, Italy compounds modulate ureter function. 3Department of Urology, Albert Ludwigs University, Freiburg, Germany Methods: The expression of TRPA1 in rat ureter tissue was studied by im- 4Department of Urology, Leuven munofluorescence. The TRPA1 distribution was compared to calcitonin gene‐ University, Leuven, Belgium related peptide (CGRP), α‐actin (SMA1), anoctamin‐1 (ANO1), and c‐kit. For 5 Department of Urology, University in vivo analyses, a catheter was implanted in the right ureter of 50 rats. Ureter College of London, London, UK peristalsis and pressures were continuously recorded by a data acquisition set‐ 6Department of Clinical and Experimental Pharmacology, Lund University, Lund, up during intraluminal infusion of saline (baseline), saline plus protamine Sweden sulfate (PS; to disrupt the urothelium), saline plus PS with hydrogen sulfide 7Department of Drug Research and (NaHS) or cinnamaldehyde (CA). Comparisons were made between rats Pharmacology, Linköping University, treated systemically with vehicle or a TRPA1‐antagonist (HC030031). Linköping, Sweden Results: TRPA1‐immunoreactive nerves co‐expressed CGRP and were mainly Correspondence located in the suburothelial region of the ureter. Immunoreactivity for TRPA1 Philipp Weinhold, Department of Urology, ‐ ‐ ‐ Ludwig‐Maximilians‐Universität was also encountered in c kit positive but ANO1 negative cells of the ureter München, Marchioninistraße 15, 81377 suburothelium and wall. Munich, Germany. In vivo, HC030031‐treated rats had elevated baseline peristaltic frequency Email: [email protected] muenchen.de (p < 0.05) and higher intraluminal pressures (p < 0.01). PS increased the frequency of ureter peristalsis versus baseline in vehicle‐treated rats (p <0.001)butnotin Funding information HC030031‐treated rats. CA (p <0.001) and NaHS (p < 0.001) decreased ureter Gester Foundation, Helsingborg, Sweden peristalsis. This was counteracted by HC030031 (p <0.05and p <0.01). Conclusions: In rats, TRPA1 is expressed on cellular structures considered of importance for peristaltic and mechanoafferent functions of the ureter. Functional data indicate that TRPA1‐mediated signals regulate ureter peri- stalsis. This effect was pronounced after mucosal disruption and suggests a role for TRPA1 in ureter pathologies involving urothelial damage. KEYWORDS ankyrin 1, cinnamaldehyde, H2S, interstitial cell, nerve, pacing ------------------------------------------------------------------------------------------------------------------------------------------- This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. © 2020 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC Neurourology and Urodynamics. 2021;40:147–157. wileyonlinelibrary.com/journal/nau | 147 148 | WEINHOLD ET AL. 1 | INTRODUCTION 2 | MATERIALS AND METHODS The ureters ensure unidirectional transport of urine 2.1 | Ethical considerations from the kidneys to the urinary bladder by peristalsis that is described to involve activities of pacemaker All experiments were approved by the Institutional Animal cells, mechanosensory signals, and electromechanical Ethics Care and Use Committees of the Lund and Linköping ‐ coupling of myogenic functions.1 3 The interface be- Universities, Sweden, and San Raffaele Scientific Institute, tween components of the ureter peristalsis system is Milan, Italy. Experiments were carried out in accordance not fully known. Electrical recordings during with the ARRIVE Guidelines.11 pyeloureteric motility have been correlated to peri- stalsis in various species and the pacing of such signals are proposed to arise from atypical smooth muscle cells 2.2 | Animals and interstitial cells of Cajal‐like cells (ICC‐LC).1,3,4 Plasticity in the expression or function of these cells are Fifty male Sprague–Dawley rats (250–300 g; Charles proposed to cause discordant regulation of ureter River) were used. Animals were maintained under stan- peristalsis in relation to vesicoureteral reflux, con- dard laboratory conditions with a 12:12 h light:dark cycle, genital ureteropelvic junction obstruction, and free access to food, water, and enrichments. Isoflurane obstructive megaureter.2,3 (alveolar concentration of 5% for induction and 2% for Besides its barrier function, the mucosa of the ur- maintenance) was used as anesthesia. After experiments, inary tract is a sensory unit that responds to mechan- rats were killed during anesthesia by carbon dioxide as- ical or chemical provocation with local release of phyxia. Ureters were harvested for immunofluorescence factors that regulate activities of other cell types that investigations from six naive separate male rats. are involved in, for example, motor functions, cell turn‐over, inflammation, or pain perception.5 As such, pressure‐dependent signals from the urothelium has 2.3 | Immunofluorescence been reported to modify the activity of sensory neurons of the perfused ureter, and capsaicin‐dependent sig- Ureter specimens were processed for immuno- nals and tachykinins are reported to modify sponta- fluorescence as previously described.12 Primary anti- neous contractile activities of upper urinary tract bodies: rabbit anti‐TRPA1 (1:500; Alomone Labs), guinea preparations.3,6 Cellular structures within the ureter pig anti‐calcitonin gene‐related peptide (CGRP; a marker mucosa, that is, the urothelium, interstitial cells, and for sensory nerves, 1:750; Euro‐Diagnostica), mouse anti‐ neurons, are express multimodal transient receptor smooth muscle α‐actin (SMA; 1:1000; Abcam), goat anti‐ potential ion channels (TRPs) that respond to chemi- anoctamin‐1 (ANO1; a marker for interstitial cells, 1:250; cal, mechanical, and thermal stimuli.7,8 Information is Santa Cruz), and a mouse anti‐c‐kit (a marker for inter- scarce on the functional role of TRPs in normal ureter stitial cells, 1:250; Santa Cruz). Secondary antibodies: peristalsis or ureter disease. The ankyrin 1 subtype Alexa Fluor, Molecular Probes Inc. (1:800). Sections were TRP (TRPA1) has been located to sensory neurons, and analyzed using a laser fluorescence microscope (Olympus interstitial cells of the proximal human ureter, and Corporation). Images were acquired using Viewfinder TRPA1‐mediated signals have been proposed involved Lite version 2.0 (Pixera Corp.). in modulation of neuromuscular functions of the isolated human and pig ureters.8,9 The TRPA1 is a cold‐ and mechanoreceptor that also acts as a sensor to 2.4 | In vivo experimental procedures irritants and bacterial lipopolysaccharides, is activated by hypoxia, and is described to be involved in neu- Animals were randomized to experimental groups roinflammatory responses of viscera.8,10 If TRPA1‐ (QuickCalcs; GraphPad Software Inc.). Briefly, during related transmission is involved in the regulation of anesthesia, an abdominal incision was performed. A ureter peristalsis has, to the best of our knowledge, not polyethylene catheter (PE‐10; Clay‐Adams) was introduced been explored. Therefore, the aim of this study was to into the ureteropelvic junction of the left ureter.13 investigate the effects by various TRPA1‐active com- The catheter was attached to a microsyringe pump (CMA pounds on ureter peristalsis in vivo in a rat model. In 100; Carnegie Medicine AB) and connected to a pressure addition, we assessed the expression of TRPA1 in the transducer (see Supplementary Information). Room tem- rat ureter in comparison to our previous findings of the perature physiological saline was infused at a speed of − human ureter.8 0.4 ml h 1 simulating normal urine production.13 Ureteral WEINHOLD ET AL. | 149 intraluminal pressure was recorded with an MP100 data also expressed immunoreactivity for CGRP (Figure 2). acquisition system (Biopac Systems Inc.). The bladder Intense TRPA1 immunoreactivity was also located in cells was incised to avoid interference on ureter pressures from interspersed in the suburothelial region (Figures 1 and 2). detrusor contractions.13 Single TRPA1‐positive cells were encountered in the In pilot experiments (data not shown), the TRPA1 muscular layer of the ureter wall (Figure 1). Co‐stainings of agonists did not effect ureter peristalsis or pressures when sectioned rat ureter tissue with antibodies for TRPA1 given intraluminally in naive rats. Therefore, after a base- and ANO1 disclosed no overlap of immunoreactivities line registration (20–30 min) with a saline infusion to (Figure 2) In contrast, TRPA1‐immunoreactive cells also achieve stable autonomous peristaltic ureter activity, an expressed c‐kit‐immunoreactivity (Figure 2). infusion with a protamine sulfate (PS)‐containing (10 mg/ ml) saline solution to disrupt the
Load more

Recommended publications
  • Expression Profiling of Ion Channel Genes Predicts Clinical Outcome in Breast Cancer
    UCSF UC San Francisco Previously Published Works Title Expression profiling of ion channel genes predicts clinical outcome in breast cancer Permalink https://escholarship.org/uc/item/1zq9j4nw Journal Molecular Cancer, 12(1) ISSN 1476-4598 Authors Ko, Jae-Hong Ko, Eun A Gu, Wanjun et al. Publication Date 2013-09-22 DOI http://dx.doi.org/10.1186/1476-4598-12-106 Peer reviewed eScholarship.org Powered by the California Digital Library University of California Ko et al. Molecular Cancer 2013, 12:106 http://www.molecular-cancer.com/content/12/1/106 RESEARCH Open Access Expression profiling of ion channel genes predicts clinical outcome in breast cancer Jae-Hong Ko1, Eun A Ko2, Wanjun Gu3, Inja Lim1, Hyoweon Bang1* and Tong Zhou4,5* Abstract Background: Ion channels play a critical role in a wide variety of biological processes, including the development of human cancer. However, the overall impact of ion channels on tumorigenicity in breast cancer remains controversial. Methods: We conduct microarray meta-analysis on 280 ion channel genes. We identify candidate ion channels that are implicated in breast cancer based on gene expression profiling. We test the relationship between the expression of ion channel genes and p53 mutation status, ER status, and histological tumor grade in the discovery cohort. A molecular signature consisting of ion channel genes (IC30) is identified by Spearman’s rank correlation test conducted between tumor grade and gene expression. A risk scoring system is developed based on IC30. We test the prognostic power of IC30 in the discovery and seven validation cohorts by both Cox proportional hazard regression and log-rank test.
    [Show full text]
  • Goblet Cell LRRC26 Regulates BK Channel Activation and Protects Against Colitis in Mice
    Goblet cell LRRC26 regulates BK channel activation and protects against colitis in mice Vivian Gonzalez-Pereza,1, Pedro L. Martinez-Espinosaa, Monica Sala-Rabanala, Nikhil Bharadwaja, Xiao-Ming Xiaa, Albert C. Chena,b, David Alvaradoc, Jenny K. Gustafssonc,d,e, Hongzhen Hua, Matthew A. Ciorbab, and Christopher J. Linglea aDepartment of Anesthesiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110; bMcKelvey School of Engineering, Washington University in St. Louis, St. Louis, MO 63130; cDepartment of Internal Medicine, Division of Gastroenterology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110; dDepartment of Medical Chemistry and Cell Biology, University of Gothenburg, 405 30 Gothenburg, Sweden; and eDepartment of Physiology, University of Gothenburg, 405 30 Gothenburg, Sweden Edited by Richard W. Aldrich, The University of Texas at Austin, Austin, TX, and approved December 21, 2020 (received for review September 16, 2020) Goblet cells (GCs) are specialized cells of the intestinal epithelium Despite this progress, ionic transport in GCs and its implications contributing critically to mucosal homeostasis. One of the func- in GC physiology is a topic that remains poorly understood. tions of GCs is to produce and secrete MUC2, the mucin that forms Here, we address the role of the Ca2+- and voltage-activated K+ the scaffold of the intestinal mucus layer coating the epithelium channel (BK channel) in GCs. and separates the luminal pathogens and commensal microbiota GCs play two primary roles: One related to the maintenance from the host tissues. Although a variety of ion channels and of the mucosal barrier (reviewed in refs.
    [Show full text]
  • Anoctamin 1 (Tmem16a) Ca -Activated Chloride Channel Stoichiometrically Interacts with an Ezrin–Radixin–Moesin Network
    Anoctamin 1 (Tmem16A) Ca2+-activated chloride channel stoichiometrically interacts with an ezrin–radixin–moesin network Patricia Perez-Cornejoa,1, Avanti Gokhaleb,1, Charity Duranb,1, Yuanyuan Cuib, Qinghuan Xiaob, H. Criss Hartzellb,2, and Victor Faundezb,2 aPhysiology Department, School of Medicine, Universidad Autónoma de San Luis Potosí, San Luis Potosí, SLP 78210, Mexico; and bDepartment of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322 Edited by David E. Clapham, Howard Hughes Medical Institute, Children’s Hospital Boston, Boston, MA, and approved May 9, 2012 (received for review January 4, 2012) The newly discovered Ca2+-activated Cl− channel (CaCC), Anocta- approach to identify Ano1-interacting proteins. We find that min 1 (Ano1 or TMEM16A), has been implicated in vital physiolog- Ano1 forms a complex with two high stochiometry interactomes. ical functions including epithelial fluid secretion, gut motility, and One protein network is centered on the signaling/scaffolding smooth muscle tone. Overexpression of Ano1 in HEK cells or Xen- actin-binding regulatory proteins ezrin, radixin, moesin, and opus oocytes is sufficient to generate Ca2+-activated Cl− currents, RhoA. The ezrin–radixin–moesin (ERM) proteins organize the but the details of channel composition and the regulatory factors cortical cytoskeleton by linking actin to the plasma membrane that control channel biology are incompletely understood. We and coordinate cell signaling events by scaffolding signaling used a highly sensitive quantitative SILAC proteomics approach molecules (19). The other major interactome is centered on the to obtain insights into stoichiometric protein networks associated SNARE and SM proteins VAMP3, syntaxins 2 and -4, and the with the Ano1 channel.
    [Show full text]
  • 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.
    [Show full text]
  • Figure S1. Development of YK Resistant Cell Lines. (A) A4573-R Tolerated a Maximum YK Concentration of 3.475 Μm with the Most Recent IC50 Value of 14.90 Μm
    Figure S1. Development of YK resistant cell lines. (A) A4573-R tolerated a maximum YK concentration of 3.475 µM with the most recent IC50 value of 14.90 µM. (B) TC71-R tolerated a maximum YK concentration of 0.876 µM with the most recent IC50 value of 1.857 µM. Drops in YK concentration in media represent the time points at which resistant cells were frozen and thawed. YK, YK-4-279; R, resistant. Figure S2. Viability curves comparing sensitive and resistant TC71 cell lines with (A) YK, (B) doxorubicin, (C) etoposide and (D) vincristine. IC50 values are presented. Resistant cells demonstrated significantly reduced sensitivity to YK (P<0.0001 vs. sensitive). YK resistant cells were significantly also resistant doxorubicin (P<0.0001 vs. sensitive), but did not demonstrate cross-resistance to etoposide or vincristine. YK, YK-4-279. Figure S3. CD99 expression is increased in TC71-R cells. (A) Quantitative PCR analysis for EF, CD99 and 18S ribosomal RNA in TC71 sensitive cells and resistant cells at multiple time points. CD99 RNA expression is significantly elevated when compared with sensitive cells at all time points. ***P<0.001 and ****P<0.0001 vs. sensitive. (B) Western blot analysis of CD99 and EF in TC71 sensitive and resistant cells. Expression levels were calculated using densitometry analysis relative to sensitive cell lines. EF, EWS-FLI1. Figure S4. Quantitative PCR for upregulated genes identified through RNA sequencing in TC71 cells. Relative expres- sion was evaluated at multiple time points in resistant cells compared with sensitive cell expression. (A) Upregulated genes included ANO1, BRSK2 and IGSF21.
    [Show full text]
  • 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.
    [Show full text]
  • The Role of TRP Channels in Pain and Taste Perception
    International Journal of Molecular Sciences Review Taste the Pain: The Role of TRP Channels in Pain and Taste Perception Edwin N. Aroke 1 , Keesha L. Powell-Roach 2 , Rosario B. Jaime-Lara 3 , Markos Tesfaye 3, Abhrarup Roy 3, Pamela Jackson 1 and Paule V. Joseph 3,* 1 School of Nursing, University of Alabama at Birmingham, Birmingham, AL 35294, USA; [email protected] (E.N.A.); [email protected] (P.J.) 2 College of Nursing, University of Florida, Gainesville, FL 32611, USA; keesharoach@ufl.edu 3 Sensory Science and Metabolism Unit (SenSMet), National Institute of Nursing Research, National Institutes of Health, Bethesda, MD 20892, USA; [email protected] (R.B.J.-L.); [email protected] (M.T.); [email protected] (A.R.) * Correspondence: [email protected]; Tel.: +1-301-827-5234 Received: 27 July 2020; Accepted: 16 August 2020; Published: 18 August 2020 Abstract: Transient receptor potential (TRP) channels are a superfamily of cation transmembrane proteins that are expressed in many tissues and respond to many sensory stimuli. TRP channels play a role in sensory signaling for taste, thermosensation, mechanosensation, and nociception. Activation of TRP channels (e.g., TRPM5) in taste receptors by food/chemicals (e.g., capsaicin) is essential in the acquisition of nutrients, which fuel metabolism, growth, and development. Pain signals from these nociceptors are essential for harm avoidance. Dysfunctional TRP channels have been associated with neuropathic pain, inflammation, and reduced ability to detect taste stimuli. Humans have long recognized the relationship between taste and pain. However, the mechanisms and relationship among these taste–pain sensorial experiences are not fully understood.
    [Show full text]
  • ANO1 Plays a Critical Role in Prostatic Hyperplasia
    COMMENTARY COMMENTARY ANO1 plays a critical role in prostatic hyperplasia Umamaheswar Duvvuria,b,1 which Ano1 is regulated and (ii)whether aDepartment of Otolaryngology, University of Pittsburgh, Pittsburgh, PA 15213; and chloride flux through this channel is re- bVeterans Affairs Pittsburgh Health System, Pittsburgh, PA 15240 quired for the growth-promoting phenotype that is ascribed to ANO1 overexpression. Benign prostatic hyperplasia (BPH) is a trou- phenomenon was ascribed to chloride Cha et al. (2) shed light on these important bling problem that affects many older men transport across the epithelium, which is issues in the context of BPH and prostate worldwide (1). This condition poses a treat- controlled by calcium-activated chloride cell proliferation (Fig. 1). Through an ele- ment challenge because current pharmacologic channels (CaCCs) (see review in ref. 3). gant set of experiments, the authors dem- therapies can have untoward side effects. A The molecular identity of these channels onstrate that ANO1 plays a crucial role in the development and progression of benign better understanding of the pathogenesis of had eluded scientists for several decades prostatic hyperplasia. It is well known that BPH would allow for the development of until the anoctamin family of proteins the prostate gland is sensitive to testoster- novel therapies for this condition. The prostate was described in 2008 (4–6). The identifi- one and its active form dihydrotestosterone gland functions to secrete fluids that nourish cation of Anoctamin 1 (ANO1/ TMEM16A) (DHT). DHT is the active form of testoster- and protect sperm. One of the key mecha- as a bona fide CaCC was met with great in- one that is generated by 5α-reductase.
    [Show full text]
  • 'Targeting Chloride Transport in Autosomal Dominant
    Zurich Open Repository and Archive University of Zurich Main Library Strickhofstrasse 39 CH-8057 Zurich www.zora.uzh.ch Year: 2020 Targeting chloride transport in autosomal dominant polycystic kidney disease Jouret, François ; Devuyst, Olivier Abstract: Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent inherited kidney disease. Transepithelial fluid secretion is one of the key factors of cystogenesis in ADPKD. Multiple studies have suggested that fluid secretion across ADPKD cyst-lining cells is driven by the secretion of chloride, essentially mediated by the CFTR channel and stimulated by increased intracellular levels of 3฀,5฀-cyclic adenosine monophosphate. This review focuses on the pathophysiology of fluid secretion in ADPKD based on the pioneering studies of Jared Grantham and colleagues, and on the follow-up investigations from the molecular level to the potential applications in ADPKD patients. Altogether, the studies of fluid and chloride transport in ADPKD paved the way for innovative therapeutic targets to prevent cyst volume expansion and thus, kidney disease progression. DOI: https://doi.org/10.1016/j.cellsig.2020.109703 Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-189492 Journal Article Published Version The following work is licensed under a Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) License. Originally published at: Jouret, François; Devuyst, Olivier (2020). Targeting chloride transport
    [Show full text]
  • Pain-Enhancing Mechanism Through Interaction Between TRPV1 and Anoctamin 1 in Sensory Neurons
    Pain-enhancing mechanism through interaction between TRPV1 and anoctamin 1 in sensory neurons Yasunori Takayamaa, Daisuke Utab, Hidemasa Furuec,d, and Makoto Tominagaa,d,1 aDivision of Cell Signaling, Okazaki Institute for Integrative Bioscience, Okazaki 444-8787, Japan; bDepartment of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan; cDivision of Neural Signaling, National Institute for Physiological Sciences, Okazaki 444-8787, Japan; and dDepartment of Physiological Sciences, Graduate University for Advanced Studies, Okazaki 444-8787, Japan Edited by David Julius, University of California, San Francisco, CA, and approved March 20, 2015 (received for review November 11, 2014) The capsaicin receptor transient receptor potential cation channel channels. Mammalian TRPV1 is activated by noxious heat, acid, and vanilloid 1 (TRPV1) is activated by various noxious stimuli, and the many chemical compounds including capsaicin (16–18). The calcium stimuli are converted into electrical signals in primary sensory permeability of TRPV1 is more than 10 times that of sodium, neurons. It is believed that cation influx through TRPV1 causes suggesting that TRPV1 could activate anoctamins readily, leading depolarization, leading to the activation of voltage-gated sodium to further depolarization. ANO1 plays an important role in noci- channels, followed by the generation of action potential. Here we ception in primary sensory neurons (19), and bradykinin-induced report that the capsaicin-evoked action potential could be induced and neuropathic pain-related behaviors were reduced in ANO1 by two components: a cation influx-mediated depolarization caused conditional-knockout mice (20, 21), suggesting that interaction be- by TRPV1 activation and a subsequent anion efflux-mediated de- tween the two proteins could strongly enhance nociceptive signals.
    [Show full text]
  • Calcium- and Voltage-Dependent Dual Gating ANO1 Is an Intrinsic Determinant of Repolarization in Rod Bipolar Cells of the Mouse Retina
    cells Article Calcium- and Voltage-Dependent Dual Gating ANO1 is an Intrinsic Determinant of Repolarization in Rod Bipolar Cells of the Mouse Retina 1, 1, 1,2, Sun-Sook Paik y, Yong Soo Park y and In-Beom Kim * 1 Department of Anatomy, College of Medicine, The Catholic University of Korea, Seoul 100744, Korea; [email protected] (S.-S.P.); [email protected] (Y.S.P.) 2 Catholic Institute for Applied Anatomy, College of Medicine, The Catholic University of Korea, Seoul 100744, Korea * Correspondence: [email protected]; Tel.: +82-2-2258-7263; Fax: +82-2-536-3110 These authors contributed equally to this work. y Received: 17 January 2020; Accepted: 24 February 2020; Published: 26 February 2020 2+ Abstract: TMEM16A/anoctamin1 (ANO1), a calcium (Ca )-activated chloride (Cl−) channel, has many functions in various excitable cells and modulates excitability in both Ca2+- and voltage-gating modes. However, its gating characteristics and role in primary neural cells remain unclear. Here, we characterized its Ca2+- and voltage-dependent components in rod bipolar cells using dissociated and slice preparations of the mouse retina. The I-V curves of Ca2+-dependent ANO1 tail current and voltage-gated Ca2+ channel (VGCC) are similar; as ANO1 is blocked by VGCC inhibitors, ANO1 may be gated by Ca2+ influx through VGCC. The voltage-dependent component of ANO1 has outward rectifying and sustained characteristics and is clearly isolated by the inhibitory effect of Cl− reduction and T16Ainh-A01, a selective ANO1 inhibitor, in high EGTA, a Ca2+ chelator. The voltage-dependent component disappears due to VGCC inhibition, suggesting that Ca2+ is the essential trigger for ANO1.
    [Show full text]
  • Detection of H3k4me3 Identifies Neurohiv Signatures, Genomic
    viruses Article Detection of H3K4me3 Identifies NeuroHIV Signatures, Genomic Effects of Methamphetamine and Addiction Pathways in Postmortem HIV+ Brain Specimens that Are Not Amenable to Transcriptome Analysis Liana Basova 1, Alexander Lindsey 1, Anne Marie McGovern 1, Ronald J. Ellis 2 and Maria Cecilia Garibaldi Marcondes 1,* 1 San Diego Biomedical Research Institute, San Diego, CA 92121, USA; [email protected] (L.B.); [email protected] (A.L.); [email protected] (A.M.M.) 2 Departments of Neurosciences and Psychiatry, University of California San Diego, San Diego, CA 92103, USA; [email protected] * Correspondence: [email protected] Abstract: Human postmortem specimens are extremely valuable resources for investigating trans- lational hypotheses. Tissue repositories collect clinically assessed specimens from people with and without HIV, including age, viral load, treatments, substance use patterns and cognitive functions. One challenge is the limited number of specimens suitable for transcriptional studies, mainly due to poor RNA quality resulting from long postmortem intervals. We hypothesized that epigenomic Citation: Basova, L.; Lindsey, A.; signatures would be more stable than RNA for assessing global changes associated with outcomes McGovern, A.M.; Ellis, R.J.; of interest. We found that H3K27Ac or RNA Polymerase (Pol) were not consistently detected by Marcondes, M.C.G. Detection of H3K4me3 Identifies NeuroHIV Chromatin Immunoprecipitation (ChIP), while the enhancer H3K4me3 histone modification was Signatures, Genomic Effects of abundant and stable up to the 72 h postmortem. We tested our ability to use H3K4me3 in human Methamphetamine and Addiction prefrontal cortex from HIV+ individuals meeting criteria for methamphetamine use disorder or not Pathways in Postmortem HIV+ Brain (Meth +/−) which exhibited poor RNA quality and were not suitable for transcriptional profiling.
    [Show full text]