chloride channels

Summary

Summary: Cell membrane glycoproteins selective for chloride ions.

Top Publications

  1. doi Ca2+-activated Cl− currents are dispensable for olfaction
    Gwendolyn M Billig
    Leibniz Institut für Molekulare Pharmakologie FMP Max Delbrück Centrum für Molekulare Medizin MDC, Berlin, Germany
    Nat Neurosci 14:763-9. 2011
  2. pmc Drosophila bestrophin-1 chloride current is dually regulated by calcium and cell volume
    Li Ting Chien
    Department of Cell Biology, Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA 30322, USA
    J Gen Physiol 130:513-24. 2007
  3. pmc Structure of a eukaryotic CLC transporter defines an intermediate state in the transport cycle
    Liang Feng
    Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, Howard Hughes Medical Institute, 1230 York Avenue, New York, NY 10065, USA
    Science 330:635-41. 2010
  4. pmc Reversal of RNA dominance by displacement of protein sequestered on triplet repeat RNA
    Thurman M Wheeler
    Departments of Neurology, Pharmacology and Physiology, University of Rochester, Rochester, NY 14642, USA
    Science 325:336-9. 2009
  5. ncbi Loss of the muscle-specific chloride channel in type 1 myotonic dystrophy due to misregulated alternative splicing
    Nicolas Charlet-B
    Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA
    Mol Cell 10:45-53. 2002
  6. pmc Chloride channels as drug targets
    Alan S Verkman
    Departments of Medicine and Physiology, University of California, San Francisco, California 94143 0521, USA
    Nat Rev Drug Discov 8:153-71. 2009
  7. ncbi Calcium-activated chloride channels
    Criss Hartzell
    Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    Annu Rev Physiol 67:719-58. 2005
  8. doi Anoctamins
    Karl Kunzelmann
    Institut fur Physiologie, Universitat Regensburg, Universitätsstraße 31, Regensburg, Germany
    Pflugers Arch 462:195-208. 2011
  9. pmc The novel marker, DOG1, is expressed ubiquitously in gastrointestinal stromal tumors irrespective of KIT or PDGFRA mutation status
    Robert B West
    Department of Pathology, Stanford University Medical Center, 300 Pasteur Drive, Stanford, CA 94305, USA
    Am J Pathol 165:107-13. 2004
  10. ncbi Expanded CUG repeats trigger aberrant splicing of ClC-1 chloride channel pre-mRNA and hyperexcitability of skeletal muscle in myotonic dystrophy
    Ami Mankodi
    Department of Neurology, School of Medicine and Dentistry, University of Rochester, Box 673, 601 Elmwood Avenue, New York 14642, USA
    Mol Cell 10:35-44. 2002

Detail Information

Publications351 found, 100 shown here

  1. doi Ca2+-activated Cl− currents are dispensable for olfaction
    Gwendolyn M Billig
    Leibniz Institut für Molekulare Pharmakologie FMP Max Delbrück Centrum für Molekulare Medizin MDC, Berlin, Germany
    Nat Neurosci 14:763-9. 2011
    ..In contrast with the current view, cyclic nucleotide-gated cation channels do not need a boost by Cl(-) channels to achieve near-physiological levels of olfaction...
  2. pmc Drosophila bestrophin-1 chloride current is dually regulated by calcium and cell volume
    Li Ting Chien
    Department of Cell Biology, Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA 30322, USA
    J Gen Physiol 130:513-24. 2007
    ..We conclude that in addition to being regulated by intracellular Ca(2+), Drosophila bestrophins are also novel members of the volume-regulated anion channel (VRAC) family that are necessary for cell volume homeostasis...
  3. pmc Structure of a eukaryotic CLC transporter defines an intermediate state in the transport cycle
    Liang Feng
    Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, Howard Hughes Medical Institute, 1230 York Avenue, New York, NY 10065, USA
    Science 330:635-41. 2010
    ..Comparison with prokaryotic CLC shows that a gating glutamate residue changes conformation and suggests a basis for 2:1 Cl(-)/H(+) exchange and a simple mechanistic connection between CLC channels and transporters...
  4. pmc Reversal of RNA dominance by displacement of protein sequestered on triplet repeat RNA
    Thurman M Wheeler
    Departments of Neurology, Pharmacology and Physiology, University of Rochester, Rochester, NY 14642, USA
    Science 325:336-9. 2009
    ..These findings suggest an alternative use of antisense methods, to inhibit deleterious interactions of proteins with pathogenic RNAs...
  5. ncbi Loss of the muscle-specific chloride channel in type 1 myotonic dystrophy due to misregulated alternative splicing
    Nicolas Charlet-B
    Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA
    Mol Cell 10:45-53. 2002
    ..We propose that disruption of alternative splicing regulation causes a predominant pathological feature of DM1...
  6. pmc Chloride channels as drug targets
    Alan S Verkman
    Departments of Medicine and Physiology, University of California, San Francisco, California 94143 0521, USA
    Nat Rev Drug Discov 8:153-71. 2009
    b>Chloride channels represent a relatively under-explored target class for drug discovery as elucidation of their identity and physiological roles has lagged behind that of many other drug targets...
  7. ncbi Calcium-activated chloride channels
    Criss Hartzell
    Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    Annu Rev Physiol 67:719-58. 2005
    Calcium-activated chloride channels (CaCCs) play important roles in cellular physiology, including epithelial secretion of electrolytes and water, sensory transduction, regulation of neuronal and cardiac excitability, and regulation of ..
  8. doi Anoctamins
    Karl Kunzelmann
    Institut fur Physiologie, Universitat Regensburg, Universitätsstraße 31, Regensburg, Germany
    Pflugers Arch 462:195-208. 2011
    ..In order to understand how anoctamins produce Ca(2+)-activated Cl(-) currents, it will be necessary to obtain better insight into their molecular structure, interactions with partner proteins, and mode of activation...
  9. pmc The novel marker, DOG1, is expressed ubiquitously in gastrointestinal stromal tumors irrespective of KIT or PDGFRA mutation status
    Robert B West
    Department of Pathology, Stanford University Medical Center, 300 Pasteur Drive, Stanford, CA 94305, USA
    Am J Pathol 165:107-13. 2004
    ..Reactivity for DOG1 may aid in the diagnosis of GISTs, including PDGFRA mutants that fail to express KIT antigen, and lead to appropriate treatment with imatinib mesylate, an inhibitor of the KIT tyrosine kinase...
  10. ncbi Expanded CUG repeats trigger aberrant splicing of ClC-1 chloride channel pre-mRNA and hyperexcitability of skeletal muscle in myotonic dystrophy
    Ami Mankodi
    Department of Neurology, School of Medicine and Dentistry, University of Rochester, Box 673, 601 Elmwood Avenue, New York 14642, USA
    Mol Cell 10:35-44. 2002
    ..We propose that a transdominant effect of mutant RNA on RNA processing leads to chloride channelopathy and membrane hyperexcitability in DM...
  11. pmc The acute nociceptive signals induced by bradykinin in rat sensory neurons are mediated by inhibition of M-type K+ channels and activation of Ca2+-activated Cl- channels
    Boyi Liu
    Department of Pharmacology, Hebei Medical University, Shijiazhuang, China
    J Clin Invest 120:1240-52. 2010
    ..These results provide a framework for understanding spontaneous inflammatory pain and may suggest new drug targets for treatment of such pain...
  12. ncbi Excitatory actions of gaba during development: the nature of the nurture
    Yehezkel Ben-Ari
    Institut de Neurobiologie de la Méditerranée INMED, INSERM Unit 29, Parc Scientifique de Luminy, 13273 Marseille Cedex 09, France
    Nat Rev Neurosci 3:728-39. 2002
    ..As key elements of this cascade are activity dependent, the formation of inhibition adds an element of nurture to the construction of cortical networks...
  13. ncbi TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity
    Antonella Caputo
    Laboratorio di Genetica Molecolare, Istituto Giannina Gaslini, Genova 16148, Italy
    Science 322:590-4. 2008
    Calcium-dependent chloride channels are required for normal electrolyte and fluid secretion, olfactory perception, and neuronal and smooth muscle excitability. The molecular identity of these membrane proteins is still unclear...
  14. doi TMEM16A protein: a new identity for Ca(2+)-dependent Cl⁻ channels
    Loretta Ferrera
    Laboratory of Molecular Genetics, Istituto Giannina Gaslini, Genova, Italy
    Physiology (Bethesda) 25:357-63. 2010
    ..The recent identification of TMEM16A protein as an important component of CaCCs should allow a better understanding of their physiological role, structure-function relationship, and regulatory mechanisms...
  15. doi DOG1 antibody is a highly sensitive and specific marker for gastrointestinal stromal tumors in cytology cell blocks
    Dick G Hwang
    Dept of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Am J Clin Pathol 135:448-53. 2011
    ..KIT was positive in 46 (88%) of the GIST cases, with sensitivity dependent on the FNA method. Both markers were highly specific: KIT was negative in all 44 non-GIST cases, whereas DOG1 showed weak positivity in only 1 leiomyosarcoma...
  16. doi Expression and function of epithelial anoctamins
    Karl Kunzelmann
    Universitat Regensburg, Institut fur Physiologie, Universitätsstraße 31, Regensburg, Germany
    Exp Physiol 97:184-92. 2012
    ..Most available data on anoctamins were obtained from mouse tissues and from cultured cells, which may not be representative of native human tissues...
  17. pmc Anoctamin/TMEM16 family members are Ca2+-activated Cl- channels
    H Criss Hartzell
    Department of Cell Biology, Emory University School of Medicine, 615 Michael Street, 535 Whitehead Bldg, Atlanta, GA 30322, USA
    J Physiol 587:2127-39. 2009
    ..Some members of this family are up-regulated in a number of tumours and functional deficiency in others is linked to developmental defects...
  18. doi The spectrum of ocular phenotypes caused by mutations in the BEST1 gene
    Camiel J F Boon
    Department of Ophthalmology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Prog Retin Eye Res 28:187-205. 2009
    ..The genotype-phenotype correlations that are observed in association with BEST1 mutations are discussed. In addition, in vitro studies and animal models that clarify the pathophysiological mechanisms are reviewed...
  19. pmc Chloride channels: often enigmatic, rarely predictable
    Charity Duran
    Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA
    Annu Rev Physiol 72:95-121. 2010
    ....
  20. ncbi Volume-sensitive chloride channels involved in apoptotic volume decrease and cell death
    Y Okada
    Department of Cell Physiology, National Institute for Physiological Sciences, Okazaki 444 8585, Japan
    J Membr Biol 209:21-9. 2006
    ..The apoptosis-inducing VSOR Cl(-) channel is distinct from ClC-3 and its molecular identity remains to be determined...
  21. pmc Expression of anoctamin 1/TMEM16A by interstitial cells of Cajal is fundamental for slow wave activity in gastrointestinal muscles
    Sung Jin Hwang
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA
    J Physiol 587:4887-904. 2009
    ..Loss of function of ANO1 did not inhibit the development of ICC networks that appeared structurally normal as indicated by Kit antibodies. These data demonstrate the fundamental role of ANO1 in the generation of slow waves in GI ICC...
  22. pmc Correction of ClC-1 splicing eliminates chloride channelopathy and myotonia in mouse models of myotonic dystrophy
    Thurman M Wheeler
    Department of Neurology, University of Rochester, Rochester, New York 14618, USA
    J Clin Invest 117:3952-7. 2007
    ....
  23. pmc Studies on expression and function of the TMEM16A calcium-activated chloride channel
    Fen Huang
    Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA
    Proc Natl Acad Sci U S A 106:21413-8. 2009
    Calcium-activated chloride channels (CaCC) with similar hallmark features are present in many cell types and mediate important physiological functions including epithelial secretion, sensory signal transduction, and smooth muscle ..
  24. ncbi Noninvasive measurement of chloride concentration in rat olfactory receptor cells with use of a fluorescent dye
    H Kaneko
    Department of Applied Physics and Chemistry, Division of Bio-Informatics, The University of Electro-Communications, Chofu, Tokyo 182 - 8585, Japan
    Am J Physiol Cell Physiol 280:C1387-93. 2001
    ..They provide a starting point for the decrease in ciliary [Cl(-)] predicted to occur during transduction...
  25. pmc Distinct expression/function of potassium and chloride channels contributes to the diverse volume regulation in cortical astrocytes of GFAP/EGFP mice
    Jana Benesova
    Department of Cellular Neurophysiology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic
    PLoS ONE 7:e29725. 2012
    ..Thus, we propose that the diverse volume changes displayed by cortical astrocytes during OGD mainly result from their distinct expression patterns of ClC2 and K(2P) channels...
  26. ncbi Chloride intracellular channel 1 identified using proteomic analysis plays an important role in the radiosensitivity of HEp-2 cells via reactive oxygen species production
    Jae Sung Kim
    Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
    Proteomics 10:2589-604. 2010
    ....
  27. pmc Muscarinic activation of Ca2+-activated Cl- current in interstitial cells of Cajal
    Mei Hong Zhu
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA
    J Physiol 589:4565-82. 2011
    ..These data suggest that different ionic conductances are responsible for electrical responses elicited by bath-applied CCh and cholinergic nerve stimulation...
  28. doi Anoctamin 2/TMEM16B: a calcium-activated chloride channel in olfactory transduction
    Simone Pifferi
    SISSA, International School for Advanced Studies, and Italian Institute of Technology, SISSA Unit, via Bonomea 265, 34136 Trieste, Italy
    Exp Physiol 97:193-9. 2012
    ..Finally, we discuss the involvement of Ca(2+)-activated Cl(-) channels in the transduction process of vomeronasal sensory neurons and the physiological role of these channels in olfaction...
  29. pmc Sorting motifs of the endosomal/lysosomal CLC chloride transporters
    Tobias Stauber
    Leibniz Institut für Molekulare Pharmakologie and Max Delbrück Centrum für Molekulare Medizin, Berlin D 13125, Germany
    J Biol Chem 285:34537-48. 2010
    The CLC protein family contains plasma membrane chloride channels and the intracellular chloride-proton exchangers ClC-3-7...
  30. ncbi Cell secretome analysis using hollow fiber culture system leads to the discovery of CLIC1 protein as a novel plasma marker for nasopharyngeal carcinoma
    Ying Hwa Chang
    Institute of Biopharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
    J Proteome Res 8:5465-74. 2009
    ..Our results indicate that the analytical platform could provide a feasible strategy to profile tumor cell secretome for identifying cancer biomarkers, and CLIC1 may be a novel plasma tumor marker for NPC...
  31. doi Distinct neuropathologic phenotypes after disrupting the chloride transport proteins ClC-6 or ClC-7/Ostm1
    Sarah N R Pressey
    Pediatric Storage Disorders Laboratory, Department of Neuroscience, Centre for the Cellular Basis of Behavior, Institute of Psychiatry, King s College London, UK
    J Neuropathol Exp Neurol 69:1228-46. 2010
    ....
  32. ncbi Astrocytes from mouse brain slices express ClC-2-mediated Cl- currents regulated during development and after injury
    Judit K Makara
    Department of Physiology and Laboratory of Cellular and Molecular Physiology, Semmelweis University Medical School, Budapest, Hungary
    Mol Cell Neurosci 23:521-30. 2003
    b>Chloride channels are important for astrocytic volume regulation and K+ buffering...
  33. pmc Requirement of calcium-activated chloride channels in the activation of mouse vomeronasal neurons
    Sangseong Kim
    Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA
    Nat Commun 2:365. 2011
    ..Recently, calcium-activated chloride channels have been shown to contribute to VNO activation...
  34. pmc ClC-7 is a slowly voltage-gated 2Cl(-)/1H(+)-exchanger and requires Ostm1 for transport activity
    Lilia Leisle
    Leibniz Institut für Molekulare Pharmakologie FMP and Max Delbrück Centrum für Molekulare Medizin MDC, Berlin, Germany
    EMBO J 30:2140-52. 2011
    ..Our work suggests that gating underlies the rectification of all endosomal/lysosomal CLCs and extends the concept of voltage gating beyond channels to ion exchangers...
  35. pmc Bestrophin, the product of the Best vitelliform macular dystrophy gene (VMD2), localizes to the basolateral plasma membrane of the retinal pigment epithelium
    A D Marmorstein
    Department of Ophthalmic Research, Cole Eye Institute, and Department of Cell Biology, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland OH 44195, USA
    Proc Natl Acad Sci U S A 97:12758-63. 2000
    ..The basolateral plasma membrane localization of bestrophin suggests the possibility that bestrophin plays a role in generating the altered electrooculogram of individuals with Best disease...
  36. pmc TMEM16F forms a Ca2+-activated cation channel required for lipid scrambling in platelets during blood coagulation
    Huanghe Yang
    Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, 94143, USA
    Cell 151:111-22. 2012
    ..This study thus identifies a Ca(2+)-activated channel permeable to Ca(2+) and critical for Ca(2+)-dependent scramblase activity during blood coagulation. PAPERFLICK:..
  37. ncbi Small-molecule screen identifies inhibitors of a human intestinal calcium-activated chloride channel
    Ricardo de la Fuente
    1246 Health Sciences East Tower, Box 0521, University of California, San Francisco CA 94143 0521, USA
    Mol Pharmacol 73:758-68. 2008
    Calcium-activated chloride channels (CaCCs) are widely expressed in mammalian tissues, including intestinal epithelia, where they facilitate fluid secretion. Potent, selective CaCC inhibitors have not been available...
  38. pmc Rescue of volume-regulated anion current by bestrophin mutants with altered charge selectivity
    Li Ting Chien
    Department of Cell Biology and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA 30322, USA
    J Gen Physiol 132:537-46. 2008
    ..VRACs were identical in wild-type and best1(-/-)/best2(-/-) mice, showing that bestrophins are unlikely to be the classical VRAC in mammalian cells...
  39. ncbi A flow-activated chloride-selective membrane current in vascular endothelial cells
    A I Barakat
    Department of Mechanical and Aeronautical Engineering, University of California, Davis, CA 95616, USA
    Circ Res 85:820-8. 1999
    ..Membrane potential sensitivity to flow was unchanged by flow preconditioning that elongated and aligned the cells...
  40. pmc Functional and clinical data of Best vitelliform macular dystrophy patients with mutations in the BEST1 gene
    Giuseppe Querques
    Department of Ophthalmology, Hopital Intercommunal de Creteil, University Paris XII, Paris, France
    Mol Vis 15:2960-72. 2009
    ..To analyze functional and clinical data of Best vitelliform macular dystrophy (VMD) patients with mutations in the BEST1 gene...
  41. pmc Principles of activation and permeation in an anion-selective Cys-loop receptor
    Ryan E Hibbs
    Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA
    Nature 474:54-60. 2011
    ..GluCl provides a framework for understanding mechanisms of fast inhibitory neurotransmission and allosteric modulation of Cys-loop receptors...
  42. pmc Pathophysiology and puzzles of the volume-sensitive outwardly rectifying anion channel
    Yasunobu Okada
    Department of Cell Physiology, National Institute for Physiological Sciences, Myodaiji cho, Okazaki 444 8585, Japan
    J Physiol 587:2141-9. 2009
    ..Molecular identification of VSOR is required to address the question of how cells sense volume expansion and activate VSOR...
  43. ncbi A point mutation in a Drosophila GABA receptor confers insecticide resistance
    R H ffrench-Constant
    Department of Entomology, 237 Russell Laboratories, University of Wisconsin, Madison 53706
    Nature 363:449-51. 1993
    ....
  44. doi Tmem16b is specifically expressed in the cilia of olfactory sensory neurons
    Sebastian Rasche
    Neuroscience Research Center, Charite, Universitatsmedizin Berlin, 10117 Berlin, Germany
    Chem Senses 35:239-45. 2010
    Calcium-activated chloride channels (CaCCs) are involved in many physiological processes, including sensory signal transduction, but only little is known to date about their structure and function...
  45. ncbi A muscleblind knockout model for myotonic dystrophy
    Rahul N Kanadia
    Department of Molecular Genetics and Microbiology, Powell Gene Therapy Center, Gainesville, FL 32610, USA
    Science 302:1978-80. 2003
    ..Our results support the hypothesis that manifestations of DM can result from sequestration of specific RNA binding proteins by a repetitive element expansion in a mutant RNA...
  46. pmc Expression cloning of TMEM16A as a calcium-activated chloride channel subunit
    Björn Christian Schroeder
    Department of Physiology, Howard Hughes Medical Institute, University of California San Francisco, San Francisco, CA 94143, USA
    Cell 134:1019-29. 2008
    Calcium-activated chloride channels (CaCCs) are major regulators of sensory transduction, epithelial secretion, and smooth muscle contraction...
  47. pmc CLC channels and transporters: proteins with borderline personalities
    Alessio Accardi
    Department of Molecular Physiology and Biophysics, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
    Biochim Biophys Acta 1798:1457-64. 2010
    ..This review focuses on the recent mechanistic insights on the how the structural similarities between CLC channels and transporters translate in unexpected mechanistic analogies between these two sub-classes...
  48. ncbi Calcium-activated chloride channels: (un)known, (un)loved?
    Jan Eggermont
    Laboratory of Physiology, Katholieke Universiteit Leuven, Campus Gasthuisberg, B 3000 Leuven, Belgium
    Proc Am Thorac Soc 1:22-7. 2004
    Calcium-activated chloride channels (CaCCs) participate in many different physiologic processes such as transepithelial transport, excitability of neurons and muscle cells, and oocyte fertilization...
  49. ncbi Modulation of GABAergic transmission by activity via postsynaptic Ca2+-dependent regulation of KCC2 function
    Hubert Fiumelli
    Division of Neurobiology, Department of Molecular and Cell Biology and Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, California 94720, USA
    Neuron 48:773-86. 2005
    ..Thus, repetitive postsynaptic spiking reduces the inhibitory action of GABA through a Ca2+-dependent downregulation of KCC2 function...
  50. doi Molecular physiology of bestrophins: multifunctional membrane proteins linked to best disease and other retinopathies
    H Criss Hartzell
    Department of Cell Biology, Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    Physiol Rev 88:639-72. 2008
    ..Bestrophins are also regulated by cell volume and may be a member of the volume-regulated anion channel family...
  51. ncbi TMEM16A confers receptor-activated calcium-dependent chloride conductance
    Young Duk Yang
    Sensory Research Center, CRI, College of Pharmacy, Seoul National University, Seoul 151 742, Korea
    Nature 455:1210-5. 2008
    Calcium (Ca(2+))-activated chloride channels are fundamental mediators in numerous physiological processes including transepithelial secretion, cardiac and neuronal excitation, sensory transduction, smooth muscle contraction and ..
  52. pmc Missense mutations in a retinal pigment epithelium protein, bestrophin-1, cause retinitis pigmentosa
    Alice E Davidson
    Genetic Medicine, The University of Manchester, Manchester Academic Heath Science Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
    Am J Hum Genet 85:581-92. 2009
    ..L140V and p.D228N) caused mislocalization of bestrophin-1 from the basolateral membrane to the cytoplasm. Mutations in bestrophin-1 are increasingly recognized as an important cause of inherited retinal dystrophy...
  53. ncbi Absence of the skeletal muscle sarcolemma chloride channel ClC-1 in myotonic mice
    C A Gurnett
    Howard Hughes Medical Institute, Department of Physiology and Biophysics, University of Iowa, College of Medicine, Iowa City 52242, USA
    J Biol Chem 270:9035-8. 1995
    ..Immunohistochemistry of skeletal muscle from ADR and other mouse models of human muscle disease demonstrate that the absence of ClC-1 chloride channel is a defect specific to ADR mice...
  54. ncbi Cell-based assay for high-throughput quantitative screening of CFTR chloride transport agonists
    L V Galietta
    Department of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, California 94143-0521, USA
    Am J Physiol Cell Physiol 281:C1734-42. 2001
    ..The fluorescence assay and cell lines should facilitate the screening of novel CFTR activators and the characterization of alternative Cl(-) channels and transporters...
  55. ncbi Lysosomal pathology and osteopetrosis upon loss of H+-driven lysosomal Cl- accumulation
    Stefanie Weinert
    Leibniz Institut fur Molekulare Pharmakologie FMP, 13125 Berlin, Germany
    Science 328:1401-3. 2010
    ..This conductance was even deleterious in Clcn7(+/unc) mice. Clcn7(-/-) and Clcn7(unc/unc) mice accumulated less Cl- in lysosomes than did wild-type mice. Thus, lowered lysosomal chloride may underlie their common phenotypes...
  56. ncbi Endosomal chloride-proton exchange rather than chloride conductance is crucial for renal endocytosis
    Gaia Novarino
    Leibniz Institut für Molekulare Pharmakologie FMP and Max Delbrück Centrum für Molekulare Medizin MDC, 13125 Berlin, Germany
    Science 328:1398-401. 2010
    ..However, their proximal tubular endocytosis was also impaired. Thus, endosomal chloride concentration, which is raised by ClC-5 in exchange for protons accumulated by the H+-ATPase, may play a role in endocytosis...
  57. pmc Drug-resistant Drosophila indicate glutamate-gated chloride channels are targets for the antiparasitics nodulisporic acid and ivermectin
    N S Kane
    Merck Research Laboratories, Merck and Co, Inc, PO Box 2000, R80Y 250, Rahway, NJ 07065, USA
    Proc Natl Acad Sci U S A 97:13949-54. 2000
    ....
  58. ncbi Mutations in the VMD2 gene are associated with juvenile-onset vitelliform macular dystrophy (Best disease) and adult vitelliform macular dystrophy but not age-related macular degeneration
    F Kramer
    Institut fur Humangenetik, Universitat Wurzburg, Germany
    Eur J Hum Genet 8:286-92. 2000
    ..There were no mutations found in the AMD group. In addition, four frequent intragenic polymorphisms did not reveal allelic association of the VMD2 locus with AMD. These data exclude a direct role of VMD2 in the predisposition to AMD...
  59. pmc Crofelemer, an antisecretory antidiarrheal proanthocyanidin oligomer extracted from Croton lechleri, targets two distinct intestinal chloride channels
    Lukmanee Tradtrantip
    Department of Medicine, University of California, San Francisco, San Francisco, CA 94143 0521, USA
    Mol Pharmacol 77:69-78. 2010
    ..5 microM. The dual inhibitory action of crofelemer on two structurally unrelated prosecretory intestinal Cl(-) channels may account for its intestinal antisecretory activity...
  60. pmc Functional properties of murine bestrophin 1 channel
    Kate E O'Driscoll
    Department of Physiology and Cell Biology, University of Nevada, School of Medicine, 1664 N Virginia Street, Reno, NV 89557, USA
    Biochem Biophys Res Commun 384:476-81. 2009
    ..Our study provides the first characterization of the biophysical properties of mBest1 and a framework for the elucidation of the physiological role of bestrophins...
  61. pmc Anoctamins and gastrointestinal smooth muscle excitability
    Kenton M Sanders
    Department of Physiology and Cell Biology, University of Nevada, School of Medicine, Reno, NV 89557, USA
    Exp Physiol 97:200-6. 2012
    ..Anoctamin 1 is a prominent conductance in ICC, and these channels appear to be involved in pacemaker activity and in responses to enteric excitatory neurotransmitters...
  62. ncbi Contribution of chloride channels to volume regulation of cortical astrocytes
    Kimberly A Parkerson
    Department of Neurobiology, Civitan International Research Center, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
    Am J Physiol Cell Physiol 284:C1460-7. 2003
    ..These data suggest that Cl(-) flux through ion channels rather than transporters is essential for volume regulation of cultured astrocytes in response to hypotonic challenge...
  63. pmc Ano1 as a regulator of proliferation
    Jennifer E Stanich
    Enteric Neuroscience Program, Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota 55905, USA
    Am J Physiol Gastrointest Liver Physiol 301:G1044-51. 2011
    ..These data led us to conclude that Ano1 regulates proliferation at the G(1)/S transition of the cell cycle and may play a role in tumorigenesis...
  64. ncbi D2-like dopamine receptors promote interactions between calcium and chloride channels that diminish rod synaptic transfer in the salamander retina
    Wallace B Thoreson
    Department of Ophthalmology, University of Nebraska Medical Center, Omaha 68198 5540, USA
    Vis Neurosci 19:235-47. 2002
    ..The net result is a Cl- efflux that inhibits depolarization-evoked increases in [Ca2+]i and synaptic transmission from rods...
  65. pmc Ligand-gated chloride channels are receptors for biogenic amines in C. elegans
    Niels Ringstad
    Howard Hughes Medical Institute, Department of Biology, and McGovern Institute for Brain Research, MIT, Cambridge, MA 02139, USA
    Science 325:96-100. 2009
    ..We have identified in the nematode Caenorhabditis elegans three ligand-gated chloride channels that are receptors for biogenic amines: LGC-53 is a high-affinity dopamine receptor, LGC-55 is a high-..
  66. pmc Voltage- and calcium-dependent gating of TMEM16A/Ano1 chloride channels are physically coupled by the first intracellular loop
    Qinghuan Xiao
    Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA
    Proc Natl Acad Sci U S A 108:8891-6. 2011
    ..This mechanism provides a unified explanation of CaCC channel gating by voltage and ligand that has long been enigmatic...
  67. pmc ANOs 3-7 in the anoctamin/Tmem16 Cl- channel family are intracellular proteins
    Charity Duran
    Department of Cell Biology and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, Georgia 30322 3030, USA
    Am J Physiol Cell Physiol 302:C482-93. 2012
    ..Determining the role of anoctamin family members in ion transport will be critical to understanding their functions in physiology and disease...
  68. ncbi Volume-activated chloride currents contribute to the resting conductance and invasive migration of human glioma cells
    C B Ransom
    Department of Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
    J Neurosci 21:7674-83. 2001
    ..We propose that I(Cl,Vol) contributes to cell shape and volume changes required for glioma cell migration through brain tissue...
  69. pmc Mechanism of action of the insecticides, lindane and fipronil, on glycine receptor chloride channels
    Robiul Islam
    Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia
    Br J Pharmacol 165:2707-20. 2012
    ..We also investigated the mechanisms by which lindane and fipronil inhibit α1 glycine receptors...
  70. ncbi Two splice variants derived from a Drosophila melanogaster candidate ClC gene generate ClC-2-type Cl- channels
    Carlos A Flores
    Centro de Estudios Cientificos CECS, Valdivia, Chile
    Mol Membr Biol 23:149-56. 2006
    ....
  71. pmc The role of CLCA proteins in inflammatory airway disease
    Anand C Patel
    Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Annu Rev Physiol 71:425-49. 2009
    ....
  72. pmc Chloride regulation in the pain pathway
    Theodore J Price
    University of Arizona, Department of Pharmacology, USA
    Brain Res Rev 60:149-70. 2009
    ....
  73. pmc Detailed analysis of retinal function and morphology in a patient with autosomal recessive bestrophinopathy (ARB)
    Christina Gerth
    Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, University of Toronto, Toronto, Canada
    Doc Ophthalmol 118:239-46. 2009
    ..For the first time, high-resolution imaging provided in vivo evidence of RPE and photoreceptor involvement in ARB...
  74. ncbi Variant phenotype of Best vitelliform macular dystrophy associated with compound heterozygous mutations in VMD2
    Patrik Schatz
    Department of Ophthalmology, Lund University Hospital, Lund, Sweden
    Ophthalmic Genet 27:51-6. 2006
    ..To characterize the phenotype of members of a Swedish family with Best macular dystrophy and two distinct mutations in VMD2...
  75. doi Autosomal recessive vitelliform macular dystrophy in a large cohort of vitelliform macular dystrophy patients
    Tyson R Kinnick
    Department of Ophthalmology and Visual Sciences, Carver Family Center for Macular Degeneration, University of Iowa, Iowa City, Iowa 52242, USA
    Retina 31:581-95. 2011
    ..To report 11 cases of autosomal recessive vitelliform macular dystrophy and to compare their molecular findings and phenotypic characteristics with those of patients with the more common and well-described dominant form of the disease...
  76. pmc Residues important for nitrate/proton coupling in plant and mammalian CLC transporters
    Eun Yeong Bergsdorf
    Department of Physiology and Pathology of Ion Transport, Leibniz Institut für Molekulare Pharmakologie FMP and Max Delbrück Centrum für Molekulare Medizin MDC, D 13125 Berlin, Germany
    J Biol Chem 284:11184-93. 2009
    Members of the CLC gene family either function as chloride channels or as anion/proton exchangers. The plant AtClC-a uses the pH gradient across the vacuolar membrane to accumulate the nutrient NO(3)(-) in this organelle...
  77. ncbi Novel and homozygous BEST1 mutations in Chinese patients with Best vitelliform macular dystrophy
    Raymond L M Wong
    Department of Ophthalmology and Visual Sciences, Chinese University of Hong Kong, Kowloon, Hong Kong SAR, China
    Retina 30:820-7. 2010
    ..The purpose of this study was to investigate the BEST1 gene mutations in Chinese patients with Best vitelliform macular dystrophy (BVMD)...
  78. pmc Expression profile and protein translation of TMEM16A in murine smooth muscle
    Alison J Davis
    Division of Biomedical Sciences, St George s, University of London, London, United Kingdom
    Am J Physiol Cell Physiol 299:C948-59. 2010
    ..This study shows that TMEM16A expression is robust in murine vascular smooth muscle cells, consolidating the view that this gene is a viable candidate for the native Ca(2+)-activated Cl(-) channel in this cell type...
  79. ncbi Bestrophin gene mutations in patients with Best vitelliform macular dystrophy
    G M Caldwell
    Department of Cancer Genetics, Roswell Park Cancer Institute, 666 Elm Street, Buffalo, New York 14263, USA
    Genomics 58:98-101. 1999
    ..Finally, we have evidence that some mutations are associated with variable expression of the disease, suggesting the involvement of other factors or genes in the disease phenotype...
  80. ncbi Clinical expression of Best's vitelliform macular dystrophy in Swedish families with mutations in the bestrophin gene
    V Ponjavic
    Department of Ophthalmology, University Hospital, Lund, Sweden
    Ophthalmic Genet 20:251-7. 1999
    ..To examine the clinical phenotype of three Swedish families with Best's vitelliform macular dystrophy (BMD) and three different mutations in the recently identified bestrophin gene...
  81. ncbi A normal electro-oculography in a family affected by best disease with a novel spontaneous mutation of the BEST1 gene
    F Testa
    Department of Ophthalmology, Second University of Naples, Naples, Italy
    Br J Ophthalmol 92:1467-70. 2008
    ..To describe clinical and genetic findings in an Italian family affected by Best disease...
  82. doi Role of chloride channels in regulating the volume of acinar cells of the rabbit superior lacrimal gland
    George H Herok
    Co operative Research Centre for Eye Research and Technology, University of New South Wales, Kensington, NSW, Australia
    Invest Ophthalmol Vis Sci 49:5517-25. 2008
    ..To characterize the outward chloride currents (Cl(OR)) in single acinar cells isolated from the rabbit superior lacrimal gland (RSLG) to investigate the hypothesis that Cl(OR) may have a role in regulating the volume of RSLG acini...
  83. ncbi The avermectin receptors of Haemonchus contortus and Caenorhabditis elegans
    Darran M Yates
    Department of Biology and Biochemistry, University of Bath, Claverton Down, BA2 7AY, Bath, UK
    Int J Parasitol 33:1183-93. 2003
    ..that the avermectin/milbemycin family of anthelmintics act via specific interactions with glutamate-gated chloride channels. These channels are encoded by a small family of genes in nematodes, though the composition of the gene ..
  84. ncbi Genetic CLC-1 chloride channel deficiency modifies diaphragm muscle isometric contractile properties
    Erik van Lunteren
    Pulmonary and Critical Care Medicine, Case Western Reserve University, Louis Stokes Cleveland Department of Veterans Affairs, Cleveland, OH 44106, USA
    Respir Physiol Neurobiol 155:220-6. 2007
    ..These findings indicate that genetic CLC-1 deficiency not only affects muscle relaxation (myotonia) but also modulates diaphragm performance during the contractile phase of the contraction-relaxation cycle...
  85. ncbi Emerging roles of chloride channels in human diseases
    Livia Puljak
    Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390 8887, USA
    Biochim Biophys Acta 1762:404-13. 2006
    ..This review discusses the proposed roles of abnormal Cl(-) channel activity in the pathogenesis of human diseases...
  86. pmc Differential regulation of Ca(2+)-activated Cl(-) currents in rabbit arterial and portal vein smooth muscle cells by Ca(2+)-calmodulin-dependent kinase
    I A Greenwood
    Department of Pharmacology and Clinical Pharmacology, St George s Hospital Medical School, London, UK
    J Physiol 534:395-408. 2001
    ..5. The present study shows that regulation of Ca(2+)-dependent Cl(-) channels by CaMKII differs between arterial and portal vein myocytes...
  87. pmc Functional roles of bestrophins in ocular epithelia
    Alan D Marmorstein
    Department of Ophthalmology and Vision Science, University of Arizona, Tucson, AZ 85711, USA
    Prog Retin Eye Res 28:206-26. 2009
    ....
  88. pmc GLC-3: a novel fipronil and BIDN-sensitive, but picrotoxinin-insensitive, L-glutamate-gated chloride channel subunit from Caenorhabditis elegans
    L Horoszok
    Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY
    Br J Pharmacol 132:1247-54. 2001
    ..Expression of glc-3 cRNA in XENOPUS oocytes resulted in the formation of homo-oligomeric L-glutamate-gated chloride channels with robust and rapidly desensitizing currents, an EC(50) of 1.9+/-0.03 mM and a Hill coefficient of 1.5+/-0...
  89. ncbi Discovery of pyrrolo[2,3-b]pyrazines derivatives as submicromolar affinity activators of wild type, G551D, and F508del cystic fibrosis transmembrane conductance regulator chloride channels
    Sabrina Noel
    IPBC CNRS UMR 6187, Universite de Poitiers, 40 Avenue du Recteur Pineau, 86022 Poitiers, France
    J Pharmacol Exp Ther 319:349-59. 2006
    ..The potency of these agents indicates that compounds in this class may be of therapeutic benefit in CFTR-related diseases, including cystic fibrosis...
  90. pmc An ivermectin-sensitive glutamate-gated chloride channel from the parasitic nematode Haemonchus contortus
    Samantha McCavera
    Dept of Biology and Biochemistry, University of Bath, UK
    Mol Pharmacol 75:1347-55. 2009
    Nematode glutamate-gated chloride channels are targets of the macrocyclic lactones, the most important group of anthelmintics available...
  91. doi Morphological and functional changes in multifocal vitelliform retinopathy and biallelic mutations in BEST1
    Elisabeth Wittström
    Department of Ophthalmology, Lund University, Sweden
    Ophthalmic Genet 32:83-96. 2011
    ..To describe morphological and functional changes in a single patient with multifocal Best vitelliform macular dystrophy (BVMD) and to perform a genotype/phenotype correlation...
  92. ncbi Enhanced accumulation of A2E in individuals homozygous or heterozygous for mutations in BEST1 (VMD2)
    B Bakall
    Department of Ophthalmology and Vision Science, University of Arizona, Tucson, AZ 85724, USA
    Exp Eye Res 85:34-43. 2007
    ..Finally, the changes we observe in the granules suggest that the histopathology and eventual vision loss associated with BMD may be due to defects in the ability of the RPE to fully degrade phagocytosed photoreceptor outer segments...
  93. ncbi Differential macular and peripheral expression of bestrophin in human eyes and its implication for best disease
    Robert F Mullins
    Carver Family Center for Macular Degeneration, Department of Ophthalmology and Visual Science, The University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA
    Invest Ophthalmol Vis Sci 48:3372-80. 2007
    ..The nature of the vitelliform material and the reason the development of such lesions is usually restricted to the macula are two unsolved questions in the pathogenesis of this disorder...
  94. doi TMEM16B, a novel protein with calcium-dependent chloride channel activity, associates with a presynaptic protein complex in photoreceptor terminals
    Heidi Stohr
    Institut fur Humangenetik, Universitat Regensburg, 93053 Regensburg, Germany
    J Neurosci 29:6809-18. 2009
    ..The compartmentalized localization and the electrophysiological properties suggest TMEM16B to be a strong candidate for the long sought-after Ca(2+)-dependent chloride channel in the photoreceptor synapse...
  95. pmc Chloride conductance in the transverse tubular system of rat skeletal muscle fibres: importance in excitation-contraction coupling and fatigue
    T L Dutka
    Department of Zoology, La Trobe University, Melbourne, Victoria, Australia
    J Physiol 586:875-87. 2008
    ..When the t-system chloride conductance was eliminated, either by removal of all Cl(-) or by block of the chloride channels with 9-anthracene carboxylic acid (9-AC) or by treating muscles with phorbol 12,13-dibutyrate, there was a ..
  96. ncbi The Drosophila tweety family: molecular candidates for large-conductance Ca2+-activated Cl- channels
    Makoto Suzuki
    Department of Pharmacology, Division of Molecular Pharmacology, Jichi Medical School 3311 1, Yakushiji, Minamikawachi, Tochigi, 329 0498, Japan
    Exp Physiol 91:141-7. 2006
    ..I conclude that investigation of the tweety family will provide important information about large-conductance Cl- channel molecules...
  97. pmc Bestrophins and retinopathies
    Qinghuan Xiao
    Department of Cell Biology and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA 30322, USA
    Pflugers Arch 460:559-69. 2010
    ....
  98. pmc Expression and function of epithelial anoctamins
    Rainer Schreiber
    Institut fur Physiologie, Universitat Regensburg, Universitatsstrasse 31, D 93053 Regensburg, Germany
    J Biol Chem 285:7838-45. 2010
    ..We conclude that each tissue expresses a set of anoctamins that form cell- and tissue-specific Ca(2+)-dependent Cl(-) channels...
  99. ncbi Intracellular acidosis enhances the excitability of working muscle
    Thomas H Pedersen
    Department of Physiology, University of Aarhus, DK 8000, Denmark
    Science 305:1144-7. 2004
    ..These results implicate chloride ion channels in muscle function and emphasize that intracellular acidosis of muscle has protective effects during muscle fatigue...
  100. pmc Activation of the basolateral membrane Cl- conductance essential for electrogenic K+ secretion suppresses electrogenic Cl- secretion
    Quanhua He
    Department of Neuroscience, Cell Biology and Physiology, Wright State University Boonshoft School of Medicine, 3640 Colonel Glenn Highway, Dayton, OH 45435, USA
    Exp Physiol 96:305-16. 2011
    ..Maximal physiological Cl(-) secretion occurs only for synergistic activation mechanisms that close these basolateral membrane Cl(-) channels...
  101. ncbi Presence of a calcium-activated chloride current in mouse ventricular myocytes
    Yanfang Xu
    Division of Cardiovascular Medicine, Department of Medicine, University of California, Davis, California 95616, USA
    Am J Physiol Heart Circ Physiol 283:H302-14. 2002
    ..Niflumic acid (in the presence of 4-AP) leads to prolongation of the early repolarization. Thus this current may contribute to early repolarization of action potentials in mouse ventricular myocytes...

Research Grants85

  1. Glycine Channels and Hippocampal Excitability
    Lori McMahon; Fiscal Year: 2006
    An inhibitory role of strychnine-sensitive glycine-gated chloride channels (GlyRs) in the brain has largely been ignored, despite the known expression of these receptors throughout the CNS...
  2. Cholesterol and Sphingolipid Perturbation of Membrane Traffic in Human Disease
    Richard Pagano; Fiscal Year: 2009
    ..The following studies will examine the role of these lipids in exacerbating the symptoms of Cystic fibrosis and will be used in developing new therapeutic approaches for this disease. ..
  3. Structure and function of chloride channels and transporters
    Alessio Accardi; Fiscal Year: 2009
    DESCRIPTION (provided by applicant): Chloride channels and transporters of the CLC family play crucial roles in a myriad of physiological processes including regulation of electrical excitability of nerve and muscle cells, modulation of ..
  4. Structure and function of chloride channels and transporters
    Alessio Accardi; Fiscal Year: 2009
    DESCRIPTION (provided by applicant): Chloride channels and transporters of the CLC family play crucial roles in a myriad of physiological processes including regulation of electrical excitability of nerve and muscle cells, modulation of ..
  5. Structure and function of chloride channels and transporters
    Alessio Accardi; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): Chloride channels and transporters of the CLC family play crucial roles in a myriad of physiological processes including regulation of electrical excitability of nerve and muscle cells, modulation of ..
  6. Molecular Physiology of Myotonia and Periodic Paralysis
    Stephen Cannon; Fiscal Year: 2009
    ..Mutations of sodium channels (NaV1.4), chloride channels (ClC-1), K channels (Kir2.1), or Ca channels (CaV1...
  7. Regulation of Epithelial Sodium Channel by CFTR chloride channel
    Bakhrom Berdiev; Fiscal Year: 2009
    ....
  8. GABAERGIC INSECTICIDE TOXICOLOGY
    JOHN CASIDA; Fiscal Year: 1999
    ....
  9. GABAERGIC INSECTICIDE TOXICOLOGY
    JOHN CASIDA; Fiscal Year: 2001
    ....
  10. GABAERGIC INSECTICIDE TOXICOLOGY
    JOHN CASIDA; Fiscal Year: 2000
    ....
  11. GABAERGIC INSECTICIDE TOXICOLOGY
    JOHN CASIDA; Fiscal Year: 2002
    ....
  12. REGULATION OF THE GABA RECEPTOR-CHLORIDE ION CHANNEL
    ROCHELLE SCHWARTZ BLOOM; Fiscal Year: 1990
    ..This research should reveal the importance of these mechanisms in the actions of convulsant and anticonvulsant drugs and in the physiology of seizure activity itself...
  13. REGULATION OF THE GABA RECEPTOR-CHLORIDE ION CHANNEL
    ROCHELLE SCHWARTZ BLOOM; Fiscal Year: 1991
    ..This research should reveal the importance of these mechanisms in the actions of convulsant and anticonvulsant drugs and in the physiology of seizure activity itself...
  14. FUNCTIONAL ANALYSIS OF NOVEL GABA RECEPTOR IN DROSOPHILA
    Richard ffrench Constant; Fiscal Year: 1999
    ..He has functionally expressed in Xenopus oocytes GABA-gated chloride channels composed of homomultimers of Rdl and rescued the susceptible phenotype by P element mediated germline ..
  15. CFTR REGULATION BY TARGETED KINASE AND PHOSPHATASE
    Neil Bradbury; Fiscal Year: 1999
    ..abstract_text> ..
  16. CFTR REGULATION BY TARGETED KINASE AND PHOSPHATASE
    Neil Bradbury; Fiscal Year: 2002
    ..abstract_text> ..
  17. Pathological Evaluation of a Cystic Fibrosis Ferret Model
    John F Engelhardt; Fiscal Year: 2010
    ..This model shows classic signs of human CF disease and may be a valuable resource for the CF research community following completion of the proposed project. ..
  18. CFTR REGULATION BY TARGETED KINASE AND PHOSPHATASE
    Neil Bradbury; Fiscal Year: 2000
    ..abstract_text> ..
  19. CFTR REGULATION BY TARGETED KINASE AND PHOSPHATASE
    Neil Bradbury; Fiscal Year: 2001
    ..abstract_text> ..
  20. CFTR REGULATION BY TARGETED KINASE AND PHOSPHATASE
    Neil Bradbury; Fiscal Year: 2001
    ..abstract_text> ..
  21. Pathological Evaluation of a Cystic Fibrosis Ferret Model
    JOHN ENGELHARDT; Fiscal Year: 2009
    ..This model shows classic signs of human CF disease and may be a valuable resource for the CF research community following completion of the proposed project. ..
  22. Radiovirotherapy for Multiple Myeloma
    Stephen J Russell; Fiscal Year: 2010
    ..The studies to be pursued in this grant combine the promising novel approach of oncolytic virotherapy with the use of radioactive iodine for the treatment of this disease. ..
  23. Radiovirotherapy for Multiple Myeloma
    Stephen Russell; Fiscal Year: 2009
    ..The studies to be pursued in this grant combine the promising novel approach of oncolytic virotherapy with the use of radioactive iodine for the treatment of this disease. ..
  24. Daily genistein injections stimulate intestinal secretion: How?
    Layla Al Nakkash; Fiscal Year: 2007
    ..Furthermore, we aim to identify the suitability of genistein as a potential therapeutic for the most common lethal genetic disease in Caucasians, cystic fibrosis (CF). [unreadable] [unreadable] [unreadable]..
  25. STUDIES ON SEROTONIN RECEPTORS AND CHLORIDE CHANNELS
    Ricardo Miledi; Fiscal Year: 1991
    ..b>Chloride channels are a very important element in central and peripheral neurons as well as in muscle, secretory and ..
  26. MECHANISMS OF CEREBRAL RESISTANCE ARTERY CONTRACTION
    Joseph Brayden; Fiscal Year: 2000
    ..Specific Aim #3 will test the hypothesis that chloride channels contribute to regulation of membrane potential in cerebral arteries...
  27. MECHANISMS OF CEREBRAL RESISTANCE ARTERY CONTRACTION
    Joseph Brayden; Fiscal Year: 1999
    ..Specific Aim #3 will test the hypothesis that chloride channels contribute to regulation of membrane potential in cerebral arteries...
  28. TGF-BETA, CHLORIDE CHANNELS AND MIGRATION OF EOSINOPHILS
    DEVENDRA AGRAWAL; Fiscal Year: 2009
    ..The information obtained from this study should provide an opportunity to formulate superior therapeutic approaches in chronic asthma. ..
  29. TGF-BETA, CHLORIDE CHANNELS AND MIGRATION OF EOSINOPHILS
    Devendra K Agrawal; Fiscal Year: 2010
    ..The information obtained from this study should provide an opportunity to formulate superior therapeutic approaches in chronic asthma. ..
  30. Infant Study of Inhaled Saline in Cystic Fibrosis (ISIS) - CCC - Lead Application
    Margaret Rosenfeld; Fiscal Year: 2009
    ..This would be the first multicenter clinical trial of a pulmonary maintenance therapy specifically in infants with CF, and the first to use measures of infant lung function as an endpoint. ..
  31. Role of Myosin VI in CFTR Endocytosis in the Intestine
    Nadia Ameen; Fiscal Year: 2006
    ..anion secretion in the intestine. The additional funds provided by this award will enable the PI to expand investigations and develop collaborations as she pursues these revised specific aims. [unreadable] [unreadable]..
  32. Infant Study of Inhaled Saline in Cystic Fibrosis (ISIS) - CCC - Lead Application
    MARGARET contact ROSENFELD; Fiscal Year: 2010
    ..This would be the first multicenter clinical trial of a pulmonary maintenance therapy specifically in infants with CF, and the first to use measures of infant lung function as an endpoint. ..
  33. Role of Myosin VI in CFTR Endocytosis in the Intestine
    Nadia Ameen; Fiscal Year: 2007
    ..anion secretion in the intestine. The additional funds provided by this award will enable the PI to expand investigations and develop collaborations as she pursues these revised specific aims. [unreadable] [unreadable]..
  34. Cell Biology of CFTR in Polarized Epithelia
    James Collawn; Fiscal Year: 2009
    ..In the proposed studies, we are examining the cell surface stability of this chloride channel and the cellular mechanisms that regulate its cell surface stability. ..
  35. Cell Biology of CFTR in Polarized Epithelia
    James F Collawn; Fiscal Year: 2010
    ..In the proposed studies, we are examining the cell surface stability of this chloride channel and the cellular mechanisms that regulate its cell surface stability. ..
  36. ACTIVATION OF CFTR MUTANTS IN VIVO FOR CF THERAPY
    MITCHELL DRUMM; Fiscal Year: 1999
    ..If beta-adrenergic agonists and class-specific phospho-diesterase inhibitors can significantly increase chloride transport, it is important to carry out studies on mechanism to determine if the process can be further improved. ..
  37. CFTR Biogenesis and Function in Epithelia
    Zsuzsanna Bebok; Fiscal Year: 2009
    ..Understanding these processes are important in understanding the cellular basis for a number of lung pathologies including cystic fibrosis and chronic obstructive pulmonary disease (COPD). ..
  38. CFTR Biogenesis and Function in Epithelia
    Zsuzsa Bebok; Fiscal Year: 2010
    ..Understanding these processes are important in understanding the cellular basis for a number of lung pathologies including cystic fibrosis and chronic obstructive pulmonary disease (COPD). ..
  39. MEMBRANE PROTEIN TOPOLOGY--CYTOCHROME C
    Martin Caffrey; Fiscal Year: 1992
    ....
  40. Tissue-specific regulation of a gene essential for normal airway epithelia
    Ann Harris; Fiscal Year: 2009
    ..Translational opportunities that may arise from this work include modulating CFTR expression in vivo and the construction of efficient, tissue-specific gene therapy vectors. ..
  41. Tissue-specific regulation of a gene essential for normal airway epithelia
    Ann Harris; Fiscal Year: 2010
    ..Translational opportunities that may arise from this work include modulating CFTR expression in vivo and the construction of efficient, tissue-specific gene therapy vectors. ..
  42. Generation and validation of a comprehensive human disease mutant ORF resource
    Luke J Whitesell; Fiscal Year: 2010
    ..The never before achievable insights will dramatically improve the translation of current genetic knowledge to actual improvements in treatment and outcome for patients. ..
  43. Molecular Physiology of CLC Chloride Channels
    Tsung Yu Chen; Fiscal Year: 2010
    ..PUBLIC HEALTH RELEVANCE: This application will study CLC channels, which are chloride channels critical for chloride ion transports across cell membranes...
  44. Molecular Physiology of CLC Chloride Channels
    Tsung Yu Chen; Fiscal Year: 2010
    ..PUBLIC HEALTH RELEVANCE: This application will study CLC channels, which are chloride channels critical for chloride ion transports across cell membranes...
  45. Molecular Physiology of CLC Chloride Channels
    Tsung Yu Chen; Fiscal Year: 2009
    ..PUBLIC HEALTH RELEVANCE: This application will study CLC channels, which are chloride channels critical for chloride ion transports across cell membranes...
  46. Rescue of CFTR-deltaF508 misfolding by pharmacological and genetic suppressors
    RYAN TYLER; Fiscal Year: 2007
    ..The broad objective of our studies is to uncover leads that could translate into new treatments for cystic fibrosis. ..
  47. Rescue of CFTR-deltaF508 misfolding by pharmacological and genetic suppressors
    RYAN TYLER; Fiscal Year: 2009
    ..The broad objective of our studies is to uncover leads that could translate into new treatments for cystic fibrosis. ..
  48. CHLORIDE CHANNELS IN A MODEL EPITHELIUM--GALLBLADDER
    ARTHUR FINN; Fiscal Year: 1990
    ..We plan to characterize these apical chloride channels in physiological terms, to develop a monoclonal antibody to them, and to characterize the specific protein(s)..
  49. Physiologic membrane traffic regulation: intestinal CFTR
    Nadia Ameen; Fiscal Year: 2005
    ..intestinal tissues to determine a role for membrane traffic in regulated CFTR and other potential alternate chloride channels and anion transport...
  50. Physiologic membrane traffic regulation: intestinal CFTR
    Nadia Ameen; Fiscal Year: 2004
    ..intestinal tissues to determine a role for membrane traffic in regulated CFTR and other potential alternate chloride channels and anion transport...
  51. Physiologic membrane traffic regulation: intestinal CFTR
    Nadia Ameen; Fiscal Year: 2006
    ..intestinal tissues to determine a role for membrane traffic in regulated CFTR and other potential alternate chloride channels and anion transport...
  52. Physiologic membrane traffic regulation: intestinal CFTR
    Nadia Ameen; Fiscal Year: 2002
    ..intestinal tissues to determine a role for membrane traffic in regulated CFTR and other potential alternate chloride channels and anion transport...
  53. Physiologic membrane traffic regulation: intestinal CFTR
    Nadia Ameen; Fiscal Year: 2003
    ..intestinal tissues to determine a role for membrane traffic in regulated CFTR and other potential alternate chloride channels and anion transport...
  54. Physiologic membrane traffic regulation: intestinal CFTR
    Nadia Ameen; Fiscal Year: 2002
    ..intestinal tissues to determine a role for membrane traffic in regulated CFTR and other potential alternate chloride channels and anion transport...
  55. Mi: Modulating Osteoclast Gene Expression and Function
    Michael C Ostrowski; Fiscal Year: 2010
    ..The genetics and molecular biology of MITF suggests that the MITF pathway may provide molecular targets for certain bone disorders. ..
  56. Mi: Modulating Osteoclast Gene Expression and Function
    Michael Ostrowski; Fiscal Year: 2009
    ..The genetics and molecular biology of MITF suggests that the MITF pathway may provide molecular targets for certain bone disorders. ..
  57. Mi: Modulating Osteoclast Gene Expression and Function
    Michael Ostrowski; Fiscal Year: 2009
    ..The genetics and molecular biology of MITF suggests that the MITF pathway may provide molecular targets for certain bone disorders. ..
  58. Limiting Inflammation in the CF Lung
    Pamela Davis; Fiscal Year: 2007
    ..The name of the principal investigator/program director must be provided at the top of each printed page and each continuation page. RESEARCH GRANT TABLE OF CONTENTS PageNumbers Face Page ' Description, ..
  59. Cholesterol and Sphingolipid Perturbation of Membrane Traffic in Human Disease
    Andrew H Limper; Fiscal Year: 2010
    ..The following studies will examine the role of these lipids in exacerbating the symptoms of Cystic fibrosis and will be used in developing new therapeutic approaches for this disease. ..
  60. Cholesterol and Sphingolipid Perturbation of Membrane Traffic in Human Disease
    Andrew H Limper; Fiscal Year: 2011
    ..The following studies will examine the role of these lipids in exacerbating the symptoms of Cystic fibrosis and will be used in developing new therapeutic approaches for this disease. ..
  61. Functional Relevance of CFTR Trafficking in Vivo to Intestinal Disease
    Nadia Ameen; Fiscal Year: 2009
    ..This proposal seeks to understand the mechanisms that regulate CFTR movement into to the membrane under physiological conditions in the intestine in order to elucidate how dysfunction of CFTR leads to either CF or secretory diarrhea. ..
  62. GENERATING A FERRET MODEL OF CYSTIC FIBROSIS
    JOHN ENGELHARDT; Fiscal Year: 2003
    ..appears to stem from a large divergence in airway cell biology and varying composition of alternative chloride channels in the airway epithelium between mice and humans...
  63. Functional Relevance of CFTR Trafficking in Vivo to Intestinal Disease
    Nadia A Ameen; Fiscal Year: 2010
    ..This proposal seeks to understand the mechanisms that regulate CFTR movement into to the membrane under physiological conditions in the intestine in order to elucidate how dysfunction of CFTR leads to either CF or secretory diarrhea. ..
  64. Functional Relevance of CFTR Trafficking in Vivo to Intestinal Disease
    Nadia A Ameen; Fiscal Year: 2011
    ..This proposal seeks to understand the mechanisms that regulate CFTR movement into to the membrane under physiological conditions in the intestine in order to elucidate how dysfunction of CFTR leads to either CF or secretory diarrhea. ..
  65. Functional Relevance of CFTR Trafficking in Vivo to Intestinal Disease
    Nadia Ameen; Fiscal Year: 2009
    ..This proposal seeks to understand the mechanisms that regulate CFTR movement into to the membrane under physiological conditions in the intestine in order to elucidate how dysfunction of CFTR leads to either CF or secretory diarrhea. ..
  66. TRANSPORT MECHANISMS IN OCULAR CELL MEMBRANES
    JOSE ZADUNAISKY; Fiscal Year: 1990
    ..The experimental approach will consist of: 1) Studies of chloride channels in corneal epithelial cell membranes of the bovine and frog eyes, 2) Vesicular transport in cellular apical ..
  67. Correction of defective deltaF508-CFTR processing in cystic fibrosis
    Gergely L Lukacs; Fiscal Year: 2011
    ..The outcome of this research will include improved understanding of the CF protein and the isolation of potentially new, more efficient therapies for cystic fibrosis. ..
  68. Functional Relevance of CFTR Trafficking in Vivo to Intestinal Disease
    Nadia Ameen; Fiscal Year: 2009
    ..This proposal seeks to understand the mechanisms that regulate CFTR movement into to the membrane under physiological conditions in the intestine in order to elucidate how dysfunction of CFTR leads to either CF or secretory diarrhea. ..
  69. Glycine Channels and Hippocampal Excitability
    Lori McMahon; Fiscal Year: 2004
    An inhibitory role of strychnine-sensitive glycine-gated chloride channels (GlyRs) in the brain has largely been ignored, despite the known expression of these receptors throughout the CNS...
  70. Glycine Channels and Hippocampal Excitability
    Lori McMahon; Fiscal Year: 2005
    An inhibitory role of strychnine-sensitive glycine-gated chloride channels (GlyRs) in the brain has largely been ignored, despite the known expression of these receptors throughout the CNS...
  71. CHLORIDE CHANNELS AND GASTRIC ACID SECRETION
    John Cuppoletti; Fiscal Year: 1991
    ..Preliminary results of inhibitor and pH sensitivity suggest that the recorded single Cl- channels may participate in HC1 accumulation...
  72. CHLORIDE CHANNELS AND GASTRIC ACID SECRETION
    John Cuppoletti; Fiscal Year: 1992
    ..Preliminary results of inhibitor and pH sensitivity suggest that the recorded single Cl- channels may participate in HC1 accumulation...
  73. CHLORIDE CHANNELS AND GASTRIC ACID SECRETION
    John Cuppoletti; Fiscal Year: 1993
    ..Preliminary results of inhibitor and pH sensitivity suggest that the recorded single Cl- channels may participate in HC1 accumulation...
  74. Glycine Channels and Hippocampal Excitability
    Lori McMahon; Fiscal Year: 2002
    An inhibitory role of strychnine-sensitive glycine-gated chloride channels (GlyRs) in the brain has largely been ignored, despite the known expression of these receptors throughout the CNS...
  75. Glycine Channels and Hippocampal Excitability
    Lori McMahon; Fiscal Year: 2003
    An inhibitory role of strychnine-sensitive glycine-gated chloride channels (GlyRs) in the brain has largely been ignored, despite the known expression of these receptors throughout the CNS...
  76. PILOT STUDY--ASSESSMENT OF PUMP FUNCTION OF PURIFIED, RECONSTITUTED CFTR
    Christine Bear; Fiscal Year: 1999
    ..Finally, interruption the catalytic cycle by the addition of transition state analogues, should lead to dissipation of pump generated concentration gradients. ..