voltage gated potassium channels

Summary

Summary: Potassium channel whose permeability to ions is extremely sensitive to the transmembrane potential difference. The opening of these channels is induced by the membrane depolarization of the ACTION POTENTIAL.

Top Publications

  1. ncbi KCNQ5, a novel potassium channel broadly expressed in brain, mediates M-type currents
    B C Schroeder
    Zentrum fur Molekulare Neurobiologie Hamburg, Hamburg University, Martinistrasse 85, D 20246 Hamburg, Germany
    J Biol Chem 275:24089-95. 2000
  2. ncbi Crystal structure of a mammalian voltage-dependent Shaker family K+ channel
    Stephen B Long
    Howard Hughes Medical Institute, Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Science 309:897-903. 2005
  3. ncbi International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels
    George A Gutman
    Department of Microbiology and Molecular Genetics, University of California, Irvine, CA, USA
    Pharmacol Rev 57:473-508. 2005
  4. ncbi A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel
    M C Sanguinetti
    Eccles Program in Human Molecular Biology and Genetics, University of Utah Health Sciences Center, Salt Lake City 84112, USA
    Cell 81:299-307. 1995
  5. ncbi KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel
    H S Wang
    Institute of Molecular Cardiology, Department of Physiology and Biophysics, State University of New York at Stony Brook, Stony Brook, NY 11794, USA
    Science 282:1890-3. 1998
  6. ncbi KCNQ1 gain-of-function mutation in familial atrial fibrillation
    Yi Han Chen
    Department of Cardiology, Tongji Hospital, and Institute of Medical Genetics, Tongji University, 399 Xin Cun Road, Shanghai 200065, People s Republic of China
    Science 299:251-4. 2003
  7. ncbi A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome
    M E Curran
    Department of Human Genetics, University of Utah Health Sciences Center, Salt Lake City 84112
    Cell 80:795-803. 1995
  8. ncbi Kv3 channels: voltage-gated K+ channels designed for high-frequency repetitive firing
    B Rudy
    Dept of Physiology and Neuroscience, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA
    Trends Neurosci 24:517-26. 2001
  9. ncbi The principle of gating charge movement in a voltage-dependent K+ channel
    Youxing Jiang
    Howard Hughes Medical Institute, Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
    Nature 423:42-8. 2003
  10. ncbi The inward rectification mechanism of the HERG cardiac potassium channel
    P L Smith
    Department of Neurobiology, Harvard Medical School, Boston, MA 02114 2698, USA
    Nature 379:833-6. 1996

Research Grants

Detail Information

Publications313 found, 100 shown here

  1. ncbi KCNQ5, a novel potassium channel broadly expressed in brain, mediates M-type currents
    B C Schroeder
    Zentrum fur Molekulare Neurobiologie Hamburg, Hamburg University, Martinistrasse 85, D 20246 Hamburg, Germany
    J Biol Chem 275:24089-95. 2000
    ..A KCNQ5 splice variant found in skeletal muscle displays altered gating kinetics. This indicates a molecular diversity of channels yielding M-type currents and suggests a role for KCNQ5 in the regulation of neuronal excitability...
  2. ncbi Crystal structure of a mammalian voltage-dependent Shaker family K+ channel
    Stephen B Long
    Howard Hughes Medical Institute, Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Science 309:897-903. 2005
    ..Electrostatic properties of the side portals and positions of the T1 domain and beta subunit are consistent with electrophysiological studies of inactivation gating and with the possibility of K+ channel regulation by the beta subunit...
  3. ncbi International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels
    George A Gutman
    Department of Microbiology and Molecular Genetics, University of California, Irvine, CA, USA
    Pharmacol Rev 57:473-508. 2005
  4. ncbi A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel
    M C Sanguinetti
    Eccles Program in Human Molecular Biology and Genetics, University of Utah Health Sciences Center, Salt Lake City 84112, USA
    Cell 81:299-307. 1995
    ..Since block of IKr is a known mechanism for drug-induced cardiac arrhythmias, the finding that HERG encodes IKr channels provides a mechanistic link between certain forms of inherited and acquired LQT...
  5. ncbi KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel
    H S Wang
    Institute of Molecular Cardiology, Department of Physiology and Biophysics, State University of New York at Stony Brook, Stony Brook, NY 11794, USA
    Science 282:1890-3. 1998
    ..The biophysical properties, sensitivity to pharmacological blockade, and expression pattern of the KCNQ2 and KCNQ3 potassium channels were determined. It is concluded that both these subunits contribute to the native M-current...
  6. ncbi KCNQ1 gain-of-function mutation in familial atrial fibrillation
    Yi Han Chen
    Department of Cardiology, Tongji Hospital, and Institute of Medical Genetics, Tongji University, 399 Xin Cun Road, Shanghai 200065, People s Republic of China
    Science 299:251-4. 2003
    ..Thus, the S140G mutation is likely to initiate and maintain AF by reducing action potential duration and effective refractory period in atrial myocytes...
  7. ncbi A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome
    M E Curran
    Department of Human Genetics, University of Utah Health Sciences Center, Salt Lake City 84112
    Cell 80:795-803. 1995
    ..In one kindred, the mutation arose de novo. Northern blot analyses show that HERG is strongly expressed in the heart. These data indicate that HERG is LQT2 and suggest a likely cellular mechanism for torsade de pointes...
  8. ncbi Kv3 channels: voltage-gated K+ channels designed for high-frequency repetitive firing
    B Rudy
    Dept of Physiology and Neuroscience, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA
    Trends Neurosci 24:517-26. 2001
    ....
  9. ncbi The principle of gating charge movement in a voltage-dependent K+ channel
    Youxing Jiang
    Howard Hughes Medical Institute, Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
    Nature 423:42-8. 2003
    ..Our findings lead us to conclude that the voltage-sensor paddles operate somewhat like hydrophobic cations attached to levers, enabling the membrane electric field to open and close the pore...
  10. ncbi The inward rectification mechanism of the HERG cardiac potassium channel
    P L Smith
    Department of Neurobiology, Harvard Medical School, Boston, MA 02114 2698, USA
    Nature 379:833-6. 1996
    ..The characteristics of this gating suggest a specific role for this channel in the normal suppression of arrhythmias...
  11. ncbi A membrane-access mechanism of ion channel inhibition by voltage sensor toxins from spider venom
    Seok Yong Lee
    The Howard Hughes Medical Institute and Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
    Nature 430:232-5. 2004
    ..The apparent requirement for such access is consistent with the recent proposal that the sensor in voltage-dependent K+ channels is located at the membrane-protein interface...
  12. pmc Portability of paddle motif function and pharmacology in voltage sensors
    Abdulrasheed A Alabi
    Molecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nature 450:370-5. 2007
    ..The widespread targeting of voltage-sensor paddles by toxins demonstrates that this modular structural motif is an important pharmacological target...
  13. ncbi X-ray structure of a voltage-dependent K+ channel
    Youxing Jiang
    Howard Hughes Medical Institute, Laboratory of Molecular Neurobiology and Biophysics, Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
    Nature 423:33-41. 2003
    ..Flexible hinges suggest that the voltage-sensor paddles move in response to membrane voltage changes, carrying their positive charge across the membrane...
  14. ncbi Recovery from muscarinic modulation of M current channels requires phosphatidylinositol 4,5-bisphosphate synthesis
    Byung Chang Suh
    Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA 98195, USA
    Neuron 35:507-20. 2002
    ..Lipid phosphorylation by PI 4-kinase is required for recovery from muscarinic modulation of M current...
  15. ncbi The voltage-gated potassium channels and their relatives
    Gary Yellen
    Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nature 419:35-42. 2002
    ..The architectural modules and functional components of these sophisticated signalling molecules are becoming clear, but some important links remain to be elucidated...
  16. pmc Voltage-dependent K+ channel gating and voltage sensor toxin sensitivity depend on the mechanical state of the lipid membrane
    Daniel Schmidt
    Howard Hughes Medical Institute, Laboratory of Molecular Neurobiology and Biophysics, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 105:19276-81. 2008
    ..The dependence of VSTx1 activity on the mechanical state of the membrane leads us to hypothesize that voltage sensor toxins exert their effect by perturbing the interaction forces that exist between the channel and the membrane...
  17. ncbi Tight steric closure at the intracellular activation gate of a voltage-gated K(+) channel
    D del Camino
    Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA
    Neuron 32:649-56. 2001
    ..Either these Kv channels have a broader inner entrance than seen in the KcsA crystal, even in the closed state, or the region is highly flexible (but nevertheless remains very securely closed nearby)...
  18. pmc Structure of KCNE1 and implications for how it modulates the KCNQ1 potassium channel
    Congbao Kang
    Department of Biochemitry, Vanderbilt University, Nashville, Tennessee 37232, USA
    Biochemistry 47:7999-8006. 2008
    ..These working models for the KCNE1-KCNQ1 complexes may be used to formulate testable hypotheses for the molecular bases of disease phenotypes associated with the dozens of known inherited mutations in KCNE1 and KCNQ1...
  19. ncbi Solution structure and functional characterization of SGTx1, a modifier of Kv2.1 channel gating
    Chul Won Lee
    Department of Life Science, Kwangju Institute of Science and Technology, Kwangju 500 712, Korea
    Biochemistry 43:890-7. 2004
    ....
  20. pmc A role for voltage-gated, but not Ca2+-activated, K+ channels in regulating spontaneous contractile activity in myometrium from virgin and pregnant rats
    Philip Irving Aaronson
    Division of Asthma, Allergy and Lung Biology, King s College London, London
    Br J Pharmacol 147:815-24. 2006
    ..These results indicate that whereas BK(Ca) channels play little or no part in controlling basal rhythmicity in rat myometrium, K(V) channels appear to play a crucial role in this regard, especially during mid- and late pregnancy...
  21. pmc Preparation, functional characterization, and NMR studies of human KCNE1, a voltage-gated potassium channel accessory subunit associated with deafness and long QT syndrome
    Changlin Tian
    Department of Biochemistry, Center for Structural Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 8725, USA
    Biochemistry 46:11459-72. 2007
    ..Given that this segment overlaps with sites 57-59, which are known to play a critical role in modulating KCNQ1 channel activation kinetics, this unusual structural feature likely has considerable functional relevance...
  22. pmc Structure and hydration of membranes embedded with voltage-sensing domains
    Dmitriy Krepkiy
    Molecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nature 462:473-9. 2009
    ....
  23. ncbi Endogenous voltage-gated potassium channels in human embryonic kidney (HEK293) cells
    S P Yu
    Department of Neurology, Center for the Study of Nervous System Injury, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurosci Res 52:612-7. 1998
    ..The difference in endogenous voltage-activated currents in HEK293 and CHO cells suggest that CHO cell lines are a preferred system for exogenous K+ channel expression...
  24. ncbi Differential expression of genes encoding subthreshold-operating voltage-gated K+ channels in brain
    M J Saganich
    Department of Physiology and Neuroscience and Department of Biochemistry, New York University School of Medicine, New York, New York 10016
    J Neurosci 21:4609-24. 2001
    ..This indicates that the subthreshold current in many neurons may be complex, containing different components mediated by a number of channels with distinct properties and neuromodulatory responses...
  25. ncbi The binding site for channel blockers that rescue misprocessed human long QT syndrome type 2 ether-a-gogo-related gene (HERG) mutations
    Eckhard Ficker
    Rammelkamp Center for Education and Research, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio 44109, USA
    J Biol Chem 277:4989-98. 2002
    ..Our findings represent a first step toward the design of pharmacological chaperones that will rescue HERG K(+) channels without block...
  26. ncbi Physicochemical features of the HERG channel drug binding site
    David Fernandez
    Department of Physiology and Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, Utah 84112, USA
    J Biol Chem 279:10120-7. 2004
    ..Together, these findings assign specific residues to receptor fields predicted by pharmacophore models of hERG channel blockers and provide a refined molecular understanding of the drug binding site...
  27. ncbi KCNQ2 is a nodal K+ channel
    Jérôme J Devaux
    Department of Neurology, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104 6077, USA
    J Neurosci 24:1236-44. 2004
    ..The diminished activity of mutant KCNQ2 channels accounts for neonatal epilepsy and myokymia; the cellular locus of these effects may be axonal initial segments and nodes...
  28. pmc Gating currents associated with intramembrane charge displacement in HERG potassium channels
    David R Piper
    Department of Physiologyetics, University of Utah, Salt Lake City, UT 84112, USA
    Proc Natl Acad Sci U S A 100:10534-9. 2003
    ..Analysis of an inactivation-deficient mutant HERG channel and a Markov kinetic model suggest that HERG inactivation is coupled to activation...
  29. ncbi Voltage-sensor activation with a tarantula toxin as cargo
    L Revell Phillips
    Molecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 35 Convent Drive, MSC 3701 Bethesda, Maryland 20892 3701, USA
    Nature 436:857-60. 2005
    ..5 A from the centre of the bilayer. These results demonstrate that voltage-sensor paddles activate with a toxin as cargo, and suggest that the paddles traverse no more than the outer half of the bilayer during activation...
  30. ncbi Cell cycle-dependent expression of HERG1 and HERG1B isoforms in tumor cells
    Olivia Crociani
    Department of Experimental Pathology and Oncology, University of Firenze, Viale G B Morgagni 50, 50134 Firenze, Italy
    J Biol Chem 278:2947-55. 2003
    ..These results suggest that modulated expression of different K(+) channels is the molecular basis of a novel mechanism regulating neoplastic cell proliferation...
  31. ncbi Contactin orchestrates assembly of the septate-like junctions at the paranode in myelinated peripheral nerve
    M E Boyle
    Neurobiology Program, The Burnham Institute, La Jolla, CA 92037, USA
    Neuron 30:385-97. 2001
    ..1 and Kv1.2 potassium channels. Thus, contactin is a crucial part in the machinery that controls junctional attachment at the paranode and ultimately the physiology of myelinated nerve...
  32. ncbi Cloning and functional expression of rat eag2, a new member of the ether-à-go-go family of potassium channels and comparison of its distribution with that of eag1
    J Ludwig
    Institut für Neurale Signalverarbeitung, Zentrum fur Molekulare Neurobiologie Hamburg, Martinistrasse 52, Hamburg, D 20246, Germany
    Mol Cell Neurosci 16:59-70. 2000
    ..Thus, in neurones, this current is likely to impart a modulation in membrane conductance, which is sensitively responsive to resting internal calcium, and levels of electrical activity...
  33. ncbi KChIPs and Kv4 alpha subunits as integral components of A-type potassium channels in mammalian brain
    Kenneth J Rhodes
    Neuroscience, Wyeth Discovery Research, Princeton, New Jersey 08543, USA
    J Neurosci 24:7903-15. 2004
    ....
  34. ncbi The polar T1 interface is linked to conformational changes that open the voltage-gated potassium channel
    D L Minor
    Howard Hughes Medical Institute and Department of Physiology, University of California, San Francisco 94143, USA
    Cell 102:657-70. 2000
    ..Together, these data suggest that structural changes involving the buried polar T1 surfaces play a key role in the conformational changes leading to channel opening...
  35. ncbi Selective blocking of voltage-gated K+ channels improves experimental autoimmune encephalomyelitis and inhibits T cell activation
    C Beeton
    Laboratoire d'Immunologie, , , , , 13385 Marseille Cedex 5, France
    J Immunol 166:936-44. 2001
    ..We conclude that KTX is a potent immunosuppressive agent with beneficial effects on the neurological symptoms of EAE...
  36. pmc Coupling between voltage sensors and activation gate in voltage-gated K+ channels
    Zhe Lu
    Department of Physiology, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Gen Physiol 120:663-76. 2002
    ..One sequence is the so called S4-S5 linker distal to the voltage-sensing S4, while the other is around the COOH-terminal end of S6, a region containing the actual gate-forming residues...
  37. ncbi Structural determinants of KvLQT1 control by the KCNE family of proteins
    Y F Melman
    Section of Molecular Cardiology, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Biol Chem 276:6439-44. 2001
    ..Our results help to provide a basis for understanding the mechanism by which KCNE proteins control K(+) channel activity...
  38. ncbi Expression of ether à go-go potassium channels in human gliomas
    Stephan Patt
    Institute of Pathology Neuropathology, Friedrich Schiller University Jena, Bachstr 18, D 07740 Jena, Germany
    Neurosci Lett 368:249-53. 2004
    ..However, the hypothesis that EAG channels are related to the oncogenic process itself is only partly supported by this study...
  39. pmc Mutations of the S4-S5 linker alter activation properties of HERG potassium channels expressed in Xenopus oocytes
    M C Sanguinetti
    Eccles Program in Human Molecular Biology and Genetics, Division of Cardiology, Department of Medicine, University of Utah, Salt Lake City, UT 84112
    J Physiol 514:667-75. 1999
    ..5. The results indicate that the S4-S5 linker is a crucial component of the activation gate of HERG channels...
  40. ncbi M channels containing KCNQ2 subunits modulate norepinephrine, aspartate, and GABA release from hippocampal nerve terminals
    Maria Martire
    Institute of Pharmacology, School of Medicine, Catholic University of Sacred Heart, 00168 Rome, Italy
    J Neurosci 24:592-7. 2004
    ..These findings provide novel evidence for a major regulatory role of KCNQ2 K+ channel subunits in neurotransmitter release from rat hippocampal nerve endings...
  41. ncbi Contributions of Kv3 channels to neuronal excitability
    B Rudy
    Department of Physiology and Neuroscience, New York University of Medicine, New York 10016, USA
    Ann N Y Acad Sci 868:304-43. 1999
    ..Experimental evidence has now become available showing that Kv3.1-Kv3.2 channels play critical roles in the generation of fast-spiking properties in cortical GABAergic interneurons...
  42. ncbi Regional specificity of human ether-a'-go-go-related gene channel activation and inactivation gating
    David R Piper
    Department of Physiology, Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, Utah 84112, USA
    J Biol Chem 280:7206-17. 2005
    ..These results define regions on the S4 voltage sensor that contribute differentially to hERG activation and inactivation gating...
  43. pmc Gating charges in the activation and inactivation processes of the HERG channel
    Mei Zhang
    Department of Physiology, Virginia Commonwealth University, 1101 E Marshall St, Richmond, VA 23298, USA
    J Gen Physiol 124:703-18. 2004
    ..Furthermore, channel domain other than S4 contributes to gating charge involved in hERG's inactivation process...
  44. ncbi Molecular physiology and modulation of somatodendritic A-type potassium channels
    Henry H Jerng
    Division of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA
    Mol Cell Neurosci 27:343-69. 2004
    ....
  45. ncbi Delayed rectifier K+ currents, IK, are encoded by Kv2 alpha-subunits and regulate tonic firing in mammalian sympathetic neurons
    Sacha A Malin
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurosci 22:10094-105. 2002
    ..Expression of Kv2.2DN also results in membrane depolarization, suggesting that Kv2.1- and Kv2.2-encoded I(K) channels play distinct roles in regulating the excitability of SCG neurons...
  46. ncbi Genetic variations of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 in drug-induced long QT syndrome patients
    Aimee D C Paulussen
    Department of Pharmacogenomics, Johnson and Johnson Pharmaceutical Research and Development, Turnhoutseweg 30, Beerse, Belgium
    J Mol Med (Berl) 82:182-8. 2004
    ..We conclude that missense mutations in the examined cLQTS genes explain only a minority of aLQTS cases...
  47. pmc Molecular surface of tarantula toxins interacting with voltage sensors in K(v) channels
    Julia M Wang
    Molecular Physiology and Biophysics Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
    J Gen Physiol 123:455-67. 2004
    ..These results identify the active surface of the toxin and reveal the types of side chains that are important for interacting with voltage sensors...
  48. pmc Negative charges in the transmembrane domains of the HERG K channel are involved in the activation- and deactivation-gating processes
    Jie Liu
    Department of Physiology, Virginia Commonwealth University, Richmond 23298, USA
    J Gen Physiol 121:599-614. 2003
    ..There is no evidence for a metal ion binding site coordinated by negative charges in the transmembrane domains of HERG, as the one described for the EAG channel...
  49. pmc AKAP150 signaling complex promotes suppression of the M-current by muscarinic agonists
    Naoto Hoshi
    Department of Biophysical Genetics, Kanazawa University Graduate School of Medicine, 13 1 Takara machi, Kanazawa, Ishikawa 920 8640, Japan
    Nat Neurosci 6:564-71. 2003
    ..These inhibitors also reduced muscarinic inhibition of M-current. Our data indicate that AKAP150-bound PKC participates in receptor-induced inhibition of the M-current...
  50. ncbi The long QT syndromes: genetic basis and clinical implications
    C E Chiang
    Department of Medicine, Taipei Veterans General Hospital and National Yang Ming University School of Medicine, Taiwan
    J Am Coll Cardiol 36:1-12. 2000
    ..It seems likely that the approach of applying information from the genetics of uncommon congenital syndromes to the study of common acquired diseases will be an increasingly important one in the next millennium...
  51. ncbi HERG K(+) channel activity is regulated by changes in phosphatidyl inositol 4,5-bisphosphate
    J Bian
    Departments of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA
    Circ Res 89:1168-76. 2001
    ..Thus, dynamic regulation of HERG K(+) channels may be achieved via receptor-mediated changes in PIP2 concentrations...
  52. ncbi PIP(2) activates KCNQ channels, and its hydrolysis underlies receptor-mediated inhibition of M currents
    Hailin Zhang
    Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York University, New York, NY 10029, USA
    Neuron 37:963-75. 2003
    ..Finally, native or recombinant channels inhibited by muscarinic agonists can be activated by PIP(2). Our data strongly suggest that PIP(2) acts as a membrane-diffusible second messenger to regulate directly the activity of KCNQ currents...
  53. ncbi Localization of Caspr2 in myelinated nerves depends on axon-glia interactions and the generation of barriers along the axon
    S Poliak
    Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel
    J Neurosci 21:7568-75. 2001
    ....
  54. ncbi HERG channel dysfunction in human long QT syndrome. Intracellular transport and functional defects
    Z Zhou
    University of Wisconsin, Madison, Wisconsin 53792, USA
    J Biol Chem 273:21061-6. 1998
    ..These findings suggest that the loss of HERG channel function in LQT-2 mutations is caused by multiple mechanisms including abnormal channel processing, the generation of nonfunctional channels, and altered channel gating...
  55. ncbi MiRP1 modulates HCN2 channel expression and gating in cardiac myocytes
    Jihong Qu
    Department of Pharmacology, Columbia University, New York, NY 10032, USA
    J Biol Chem 279:43497-502. 2004
    ..The results indicate that MiRP1 acts as a beta subunit for HCN2 pacemaker channel subunits and alters channel gating at physiologically relevant voltages in cardiac cells...
  56. ncbi Molecular basis for Kv1.5 channel block: conservation of drug binding sites among voltage-gated K+ channels
    Niels Decher
    University of Utah, Department of Physiology, Eccles Institute of Human Genetics, Salt Lake City, Utah 84112, USA
    J Biol Chem 279:394-400. 2004
    ..Based on the homology models, the positions of the five amino acids identified to interact with S0100176 face toward the central cavity and overlap with putative binding sites for other blockers and voltage-gated potassium channels...
  57. ncbi The CD26-related dipeptidyl aminopeptidase-like protein DPPX is a critical component of neuronal A-type K+ channels
    Marcela S Nadal
    Department of Physiology and Neuroscience and Department of Biochemistry, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA
    Neuron 37:449-61. 2003
    ....
  58. ncbi Cloning and functional characterization of the smooth muscle ether-a-go-go-related gene K+ channel. Potential role of a conserved amino acid substitution in the S4 region
    Fouzia Shoeb
    Department of Physiology, University of Oklahoma Health Science Center, Oklahoma City 73104, USA
    J Biol Chem 278:2503-14. 2003
    ..These studies define the functional role of a novel isoform of the ether-a-go-go-related gene K(+) channel in smooth muscle...
  59. ncbi Disinactivation of N-type inactivation of voltage-gated K channels by an erbstatin analogue
    Zhi Hao Zhang
    Department of Women s Health and Bone, Wyeth Research, Collegeville, Pennsylvania 19426, USA
    J Biol Chem 279:29226-30. 2004
    ....
  60. pmc Location of KCNE1 relative to KCNQ1 in the I(KS) potassium channel by disulfide cross-linking of substituted cysteines
    David Y Chung
    Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 106:743-8. 2009
    ..Thus, the first E1 orientation strongly favors the open state, while the approximately opposite orientation favors the closed state...
  61. ncbi Bidirectional silencing and DNA methylation-sensitive methylation-spreading properties of the Kcnq1 imprinting control region map to the same regions
    Noopur Thakur
    Department of Development and Genetics, Evolution Biology Centre, Uppsala University, Norbyvagen 18A, S 752 36 Uppsala, Sweden
    J Biol Chem 278:9514-9. 2003
    ....
  62. ncbi KCNE2 protein is expressed in ventricles of different species, and changes in its expression contribute to electrical remodeling in diseased hearts
    Min Jiang
    Department of Physiology, Virginia Commonwealth UniversityRichmond, VA 23298, USA
    Circulation 109:1783-8. 2004
    ..Mutations in KCNE2 have been linked to long-QT syndrome (LQT6), yet KCNE2 protein expression in the ventricle and its functional role in native channels are not clear...
  63. ncbi Potassium channels: how genetic studies of epileptic syndromes open paths to new therapeutic targets and drugs
    E C Cooper
    Department of Neurology, Northern California Comprehensive Epilepsy Center, University of California, San Francisco 94143 0725, USA
    Epilepsia 42:49-54. 2001
    ....
  64. pmc KCNQ1 and KCNE1 in the IKs channel complex make state-dependent contacts in their extracellular domains
    Xulin Xu
    Department of Physiology and Biophysics, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298, USA
    J Gen Physiol 131:589-603. 2008
    ..We propose that E1 is not a passive partner of the Q1 channel, but instead can engage in molecular motions during I(Ks) gating...
  65. pmc A gating model for the archeal voltage-dependent K(+) channel KvAP in DPhPC and POPE:POPG decane lipid bilayers
    Daniel Schmidt
    Howard Hughes Medical Institute, Rockefeller University, New York, NY 10065, USA
    J Mol Biol 390:902-12. 2009
    ..By delaying the voltage sensor's return to the hyperpolarized conformation, VSTx1 favors the inactivated state of KvAP...
  66. ncbi Localization of the voltage-sensor toxin receptor on KvAP
    Vanessa Ruta
    Howard Hughes Medical Institute, Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
    Biochemistry 43:10071-9. 2004
    ..Some but not all toxins that bind to the voltage-sensor domain affect voltage-dependent gating of KvAP channels in lipid membranes...
  67. ncbi KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness
    C Kubisch
    Zentrum fur Molekulare Neurobiologie Hamburg, Universitat Hamburg, Germany
    Cell 96:437-46. 1999
    ..Whereas mutations in KCNQ1 cause deafness by affecting endolymph secretion, the mechanism leading to KCNQ4-related hearing loss is intrinsic to outer hair cells...
  68. ncbi Molecular and functional characterization of common polymorphisms in HERG (KCNH2) potassium channels
    Blake D Anson
    Department of Medicine, University of Wisconsin, 1300 University Ave, Madison, WI 53711, USA
    Am J Physiol Heart Circ Physiol 286:H2434-41. 2004
    ..All HERG channels had similar sensitivity to block by cisapride. Therefore, some HERG polymorphic channels are electrophysiologically different from WT channels...
  69. ncbi Association of KCNQ1, KCNE1, KCNH2 and SCN5A polymorphisms with QTc interval length in a healthy population
    Laetitia Gouas
    INSERM U582, Institut de Myologie, IFR 14, UPMC, Groupe Hospitalier Pitie Salpetriere, Paris, France
    Eur J Hum Genet 13:1213-22. 2005
    ..This suggests that genetic determinants located in KCNQ1, KCNE1, KCNH2 and SCN5A influence QTc length in healthy individuals and may represent risk factors for arrhythmias or cardiac sudden death in patients with cardiovascular diseases...
  70. pmc Molecular correlates of the M-current in cultured rat hippocampal neurons
    M M Shah
    Wellcome Laboratory for Molecular Pharmacology, Department of Pharmacology, University College London, Gower Street, UK
    J Physiol 544:29-37. 2002
    ..Our data suggest that KCNQ2, KCNQ3 and KCNQ5 subunits contribute to I(K(M)) in these neurons and that the variations in TEA sensitivity may reflect differential expression of KCNQ2, KCNQ3 and KCNQ5 subunits...
  71. pmc Inhibition of human ether à go-go potassium channels by Ca(2+)/calmodulin
    R Schönherr
    Arbeitsgruppe Molekulare und Zelluläre Biophysik, am Klinikum der Friedrich Schiller Universität Jena, Drackendorfer Strabetae 1, D 07747 Jena, Germany
    EMBO J 19:3263-71. 2000
    ..Co-expression experiments of wild-type and mutant channels revealed that the binding of one CaM molecule per channel complex is sufficient for channel inhibition...
  72. ncbi The small conductance K+ channel, KCNQ1: expression, function, and subunit composition in murine trachea
    F Grahammer
    Institute of Physiology, Albert Ludwigs Universitat, Hermann Herder Strabetae 7, D 79104 Freiburg, Germany
    J Biol Chem 276:42268-75. 2001
    ..We conclude that at least in mice a KCNQ1 channel complex seems to be the dominant basolateral K(+) conductance in tracheal epithelial cells...
  73. ncbi Inhibition of IKs channels by HMR 1556
    H Gögelein
    Aventis Pharma Deutschland GmbH, DG Cardiovascular Diseases, Frankfurt am Main, Germany
    Naunyn Schmiedebergs Arch Pharmacol 362:480-8. 2000
    ..In conclusion, HMR 1556 is a potent and selective inhibitor of the IKs current in guinea pig ventricular myocytes. The prolongation of the action potential duration is maintained at fast pacing rates...
  74. ncbi Crystal structure and functional analysis of the HERG potassium channel N terminus: a eukaryotic PAS domain
    J H Morais Cabral
    Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, New York, New York 10021, USA
    Cell 95:649-55. 1998
    ..The presence of the domain attached to the channel slows the rate of deactivation. Given the roles of PAS domains in biology, we propose that the HERG N-terminal domain has a regulatory function...
  75. ncbi MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia
    G W Abbott
    Department of Pediatrics, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06536, USA
    Cell 97:175-87. 1999
    ..A mechanism for acquired arrhythmia is revealed: genetically based reduction in potassium currents that remains clinically silent until combined with additional stressors...
  76. ncbi Voltage-gated K channels
    Clay M Armstrong
    Department of Physiology, University of Pennsylvania, Philadelphia, PA 19104 6085, USA
    Sci STKE 2003:re10. 2003
    ..More complex channels have evolved molecular "gatekeepers," allowing them to respond to appropriate stimuli by opening, closing, and inactivating...
  77. ncbi Remodeling of Kv4.3 potassium channel gene expression under the control of sex hormones
    M Song
    Department of Anesthesiology, School of Medicine, University of California at Los Angeles, California 90095 1778, USA
    J Biol Chem 276:31883-90. 2001
    ..Thus, estrogen remodels the expression of Kv4.3 in myometrium by directly diminishing its transcription and, indirectly, by altering Kv4.3 delivery to the plasma membrane...
  78. ncbi Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing
    David J Tester
    Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
    Heart Rhythm 2:507-17. 2005
    ..The purpose of this study was to determine the spectrum and prevalence of cardiac channel mutations among a large cohort of consecutive, unrelated patients referred for long QT syndrome (LQTS) genetic testing...
  79. ncbi Surface expression and single channel properties of KCNQ2/KCNQ3, M-type K+ channels involved in epilepsy
    M Schwake
    Zentrum für Molekulare Neurobiologie Hamburg ZMNH, Universitat Hamburg, Martinistrasse 85, D 20246 Hamburg, Germany
    J Biol Chem 275:13343-8. 2000
    ..Thus, the increase in currents seen upon co-expressing KCNQ2 and KCNQ3 is predominantly due to an increase in surface expression, which is dependent on an intact carboxyl terminus...
  80. pmc Induction of p57(KIP2) expression by p73beta
    Eva Balint
    Regulation of Cell Growth Laboratory, Cancer and Developmental Biology Laboratory, National Cancer Institute, Frederick, MD 21702 1201, USA
    Proc Natl Acad Sci U S A 99:3529-34. 2002
    ..Our results suggest that p73 may regulate expression of genes through mechanisms that are not shared by p53, potentially explaining the different contributions of p53 and p73 to normal development...
  81. ncbi Stoichiometry of expressed KCNQ2/KCNQ3 potassium channels and subunit composition of native ganglionic M channels deduced from block by tetraethylammonium
    Jennifer K Hadley
    Department of Pharmacology, University College London, London WC1E 6BT, United Kingdom
    J Neurosci 23:5012-9. 2003
    ....
  82. pmc Tight coupling of rubidium conductance and inactivation in human KCNQ1 potassium channels
    Guiscard Seebohm
    Department of Physiology, University of Utah, Salt Lake City, UT USA, Physiologisches Institut I, Tubingen, Germany
    J Physiol 552:369-78. 2003
    ....
  83. ncbi Hyperpolarization moves S4 sensors inward to open MVP, a methanococcal voltage-gated potassium channel
    Federico Sesti
    Department of Pediatrics, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, Connecticut 06536, USA
    Nat Neurosci 6:353-61. 2003
    ..Thus, MVP opens with sensors inward indicating a reversal of S4 position and pore state compared to classical channels. Homologous channels in mammals and plants are expected to function similarly...
  84. ncbi Solution structure and function of the "tandem inactivation domain" of the neuronal A-type potassium channel Kv1.4
    Ralph Wissmann
    Department of Physiology II, University of Freiburg, Hermann Herder Strasse 7, 79104 Freiburg, Germany
    J Biol Chem 278:16142-50. 2003
    ..Together, the concerted action of ID1 and ID2 may promote rapid inactivation of Kv1.4 that is crucial for the channel function in short term plasticity...
  85. pmc Mutations in the long QT gene, KCNQ1, are an uncommon cause of atrial fibrillation
    P T Ellinor
    Heart 90:1487-8. 2004
  86. pmc Slow gating charge immobilization in the human potassium channel Kv1.5 and its prevention by 4-aminopyridine
    D Fedida
    Department of Physiology, Queen s University, Kingston, Ontario, Canada
    J Physiol 494:377-87. 1996
    ..Some actions of 4-AP appear independent of its properties as a blocker of open K+ channels, and are not mimicked by internal TEA...
  87. ncbi T1-T1 interactions occur in ER membranes while nascent Kv peptides are still attached to ribosomes
    J Lu
    Department of Physiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6085, USA
    Biochemistry 40:10934-46. 2001
    ..ER membranes are required for this interaction, and T1-T1 interactions occur inter-polysomally. Thus, folding of the T1 domain and intersubunit interaction may represent the first assembly event in channel formation...
  88. ncbi Solution structure and lipid membrane partitioning of VSTx1, an inhibitor of the KvAP potassium channel
    Hoi Jong Jung
    Department of Life Science, Gwangju Institute of Science and Technology, Gwangju 500 712, Korea
    Biochemistry 44:6015-23. 2005
    ....
  89. pmc Intracellular domains interactions and gated motions of I(KS) potassium channel subunits
    Yoni Haitin
    Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
    EMBO J 28:1994-2005. 2009
    ..Thus, during channel gating KCNE1 is not static. Instead, the C-termini of both subunits experience molecular motions, which are disrupted by the D76N causing disease mutation...
  90. pmc KCNQ4, a K+ channel mutated in a form of dominant deafness, is expressed in the inner ear and the central auditory pathway
    T Kharkovets
    Zentrum fur Molekulare Neurobiologie Hamburg, Universitat Hamburg, Martinistrasse 85, D 20246 Hamburg, Germany
    Proc Natl Acad Sci U S A 97:4333-8. 2000
    ..This is the first ion channel shown to be specifically expressed in a sensory pathway. Moreover, the expression pattern of KCNQ4 in the mouse auditory system raises the possibility of a central component in the DFNA2 hearing loss...
  91. pmc Localization and targeting of voltage-dependent ion channels in mammalian central neurons
    Helene Vacher
    Department of Neurobiology, Physiology, and Behavior, College of Biological Sciences, University of California, Davis, California 95616 8519, USA
    Physiol Rev 88:1407-47. 2008
    ..Finally, we discuss the emerging mechanisms for determining the discrete subcellular distributions observed for many neuronal ion channels...
  92. ncbi Expression of the IKr components KCNH2 (rERG) and KCNE2 (rMiRP1) during late rat heart development
    K R J Chun
    AK St Georg, Abteilung fur Kardiologie, Lohmuhlenstrasse 5, 20099 Hamburg, Germany
    Exp Mol Med 36:367-71. 2004
    ..It seems likely that KCNH2 and KCNE2 are linked to form cardiac IKr channels, associated to cardiogenesis and cardiomyocyte excitability...
  93. ncbi Two N-terminal domains of Kv4 K(+) channels regulate binding to and modulation by KChIP1
    Robert H Scannevin
    Neuroscience Discovery Research, Wyeth Research CN 8000, Princeton, NJ 08543, USA
    Neuron 41:587-98. 2004
    ....
  94. ncbi Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel
    M C Sanguinetti
    Department of Medicine, Cardiology Division, University of Utah, Salt Lake City 84112, USA
    Nature 384:80-3. 1996
    ..Coexpression of K(V)LQT1 with minK induced a current that was almost identical to cardiac I(Ks). Therefore, K(V)LQT1 is the subunit that coassembles with minK to form I(Ks) channels and I(Ks) dysfunction is a cause of cardiac arrhythmia...
  95. ncbi Molecular determinants of dofetilide block of HERG K+ channels
    E Ficker
    Rammelkamp Center for Education and Research, MetroHealth Campus, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44109 1998, USA
    Circ Res 82:386-95. 1998
    ..Thus, the serine in position HERG 620 may participate directly in dofetilide binding; however, an intact C-type inactivation process seems to be crucial for high-affinity drug binding...
  96. ncbi KCNE1-like gene is deleted in AMME contiguous gene syndrome: identification and characterization of the human and mouse homologs
    M Piccini
    Genetica Medica, Policlinico Le Scotte, Siena, 53100, Italy
    Genomics 60:251-7. 1999
    ....
  97. pmc Electrostatic model of S4 motion in voltage-gated ion channels
    Harold Lecar
    Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720, USA
    Biophys J 85:2854-64. 2003
    ..The resulting gating-charge distributions are compared to experimental results on wild-type and charge-neutralized mutants of the Shaker K(+) channel...
  98. pmc Requirement of subunit expression for cAMP-mediated regulation of a heart potassium channel
    Junko Kurokawa
    Department of Pharmacology, College of Physicians and Surgeons of Columbia University, 630 West 168th Street, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 100:2122-7. 2003
    ..Transduction of protein phosphorylation into physiologically necessary channel function represents a previously uncharacterized role for the KCNE1 auxiliary subunit, which can be disrupted in LQT-5...
  99. ncbi Functional analysis of an archaebacterial voltage-dependent K+ channel
    Vanessa Ruta
    Howard Hughes Medical Institute, Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
    Nature 422:180-5. 2003
    ..The conservation of function reflects structural conservation in the voltage sensor as revealed by specific, high-affinity interactions with tarantula venom toxins, which evolved to inhibit eukaryotic K(V) channels...
  100. ncbi Role of the Kv4.3 K+ channel in ventricular muscle. A molecular correlate for the transient outward current
    J E Dixon
    Department of Neurobiology and Behavior, State University of New York at Stony Brook 11794 5230, USA
    Circ Res 79:659-68. 1996
    ..It is possible that the much longer ventricular action potential duration observed in canine heart compared with rat heart is due, in part, to the lower levels of Kv1.2, Kv2.1, and Kv4.2 gene expression in canine heart...
  101. ncbi Role of K(V)LQT1 in cyclic adenosine monophosphate-mediated Cl(-) secretion in human airway epithelia
    M Mall
    Universitäts Kinderklinik and Physiologisches Institut, Albert Ludwigs Universitat Freiburg, Freiburg, Germany
    Am J Respir Cell Mol Biol 23:283-9. 2000
    ..Activation of K(V)LQT1 in CF airways in parallel with stimulation of residual CF transmembrane conductance regulator Cl(-) channel activity or alternative Cl(-) channels could help to circumvent the secretory defect...

Research Grants64

  1. STRUCTURE OF AN EDITING ENZYME DSRNA ADENOSINE DEAMINASE
    Alexander Rich; Fiscal Year: 2002
    ..Knowledge of the structure of the enzyme associated with its complex substrates should provide significant insight into the manner in which this enzyme selectively alters the genetic message. ..
  2. Parvalbumin-Containing Neurons in Schizophrenia
    Tsung Ung W Woo; Fiscal Year: 2013
    ..Findings of the proposed studies are expected to shed light on the conceptualization of treatment and prevention strategies that aim at fundamentally correcting the underlying neural circuit deficits. ..
  3. The voltage-gated Kv1.3 channel in psoriatic disease: A novel therapeutic target
    Siba P Raychaudhuri; Fiscal Year: 2012
    ..3+ lymphocytes pre and post treatment in the transplanted skin. The overall goal of this proposal is to determine whether Kv1.3 blockade constitutes a potential new therapeutic approach to the treatment of psoriasis. ..
  4. New Peptides for the Treatment of Multiple Sclerosis
    Christine Beeton; Fiscal Year: 2013
    ..This project will generate novel peptide blockers of Kv1.3, which we believe will be valuable leads in the development of new treatments for MS and other chronic inflammatory diseases. ..
  5. Redox Regulation of Kv Channels
    SRINIVAS TIPPARAJU; Fiscal Year: 2013
    ..These findings could provide insights into the development of new therapeutic interventions for the treatment and management of myocardial ischemic injury. ..
  6. Functions of 5'NCRs of picornavirus and cellular mRNAs
    Bert L Semler; Fiscal Year: 2013
    ..abstract_text> ..
  7. MOLECULAR PROPERTIES OF IONIC PERMEABILITY IN NERVE
    Bertil Hille; Fiscal Year: 2012
    ..Many drugs of abuse and drugs of psychiatry act on the signaling systems studied here. The involuntary nervous system talks to its targets by the signaling mechanisms elucidated here. ..
  8. Mechanisms and Treatment of Network Dysfunction in Alzheimer's Disease
    KEITH ALAN VOSSEL; Fiscal Year: 2013
    ..The mentoring and research experience described in this proposal will facilitate the candidate's goal of developing a strong independent research career. ..
  9. The Role of KV1.3 in Effector T cells
    Peter A Calabresi; Fiscal Year: 2012
    ..Further, understanding basic mechanisms of T cell function will enhance our knowledge of how the immune system causes disease and allow us to develop novel strategies for correcting abnormal immune responses in diseases like MS. ..
  10. O2 sensing in the human and rabbit ductus arteriosus.
    Stephen L Archer; Fiscal Year: 2013
    ..Since HOSK may have arisen independent of the canonical K+ channel family, exploring its structure-function relationship will extend our fundamental knowledge K+ channels. ..
  11. Role of glycosylation in voltage-gated potassium channels
    Desiree A Thayer; Fiscal Year: 2010
    ....
  12. Molecular Regulation of an Epilepsy Modifier Gene
    BENJAMIN JORGE; Fiscal Year: 2013
    ....
  13. Towards understanding the role of sumoylation in ion channel regulation
    Sindhu Rajan; Fiscal Year: 2011
    ..We present preliminary evidence for SUMO mediated inhibition of two voltage gated potassium channels, Kv2.1 and Kv4.3. Blockage of Kv2...
  14. Neurochemistry and Genetics of Drosophila CaMKII
    Leslie C Griffith; Fiscal Year: 2013
    ..Understanding how the context of a protein's location can affect or regulate activity is critical to rational drug design and may even provide new drug targets. ..
  15. A New Family of Voltage-gated Potassium Channel Regulaory Subunits
    Steve A N Goldstein; Fiscal Year: 2011
    ..This revised application seeks to address concerns raised in the first review cycle. ..
  16. Making Sense of Voltage Sensors
    Stephen H White; Fiscal Year: 2013
    ..His work focuses directly on the molecular basis of voltage sensor domains and their interactions with VSD-blocking toxins...
  17. FLUCTUATIONS IN IONIC CURRENT THROUGH MEMBRANE CHANNELS
    FREDERICK J SIGWORTH; Fiscal Year: 2012
    ..2, one of the best-studied voltage-gated potassium channels. By creating membrane potentials in the vesicles, we will be able to trap this channel in its closed as well as open states for structure determination. ..
  18. Phosphatase Regulation of Olfactory Bulb Mitral Cell Activity
    Melissa Cavallin Johnson; Fiscal Year: 2011
    ..The link between these two proteins in the olfactory system has implications not only for sensory function but also for energy homeostasis. ..
  19. Analysis of EGFR-dependent sleep in C. elegans
    CHERYL LYNN VAN BUSKIRK; Fiscal Year: 2013
    ..We will identify this signal through RNAi-based functional genomics, and characterize its function using molecular-genetic approaches. ..
  20. Regulation of K+ Channel Gating by RNA Editing
    Sandra C Garrett; Fiscal Year: 2011
    ..Research like the proposed study promotes a basic understanding of how these channels work, which is the basis for determining how different channel related diseases occur and how they may be treated. ..
  21. Cellular regulation of Sodium-activated Ion Channels
    Leonard K Kaczmarek; Fiscal Year: 2013
    ....
  22. Slowly Inactivating K+ Channels in Neocortical Pyramidal Cells
    ROBERT C FOEHRING; Fiscal Year: 2013
    ..Time coding is important for generation of rhythmic cortical activity such as observed during attention and sensory processing. ..
  23. miRNA Regulation of Gene Expression in Alcohol Tolerance and Withdrawal
    Steven N Treistman; Fiscal Year: 2013
    ..In this project we will explore a novel mechanism, acting on gene products, which will provide important insights in our quest for this understanding. ..
  24. Mechanism of cryptochrome-mediated photo transduction
    Todd C Holmes; Fiscal Year: 2013
    ..preliminary data that membrane coupling of Cry's light activated redox state occurs through voltage gated potassium channels, we will test the hypothesis that dCry then interacts with membrane redox-sensitive effector ..
  25. Identification of the gene causing spinocerebellar ataxia in a Filipino family
    MICHAEL FARRIS WATERS; Fiscal Year: 2012
    ..abstract_text> ..
  26. Glucose Sensitivity of Mitral Cell Neurons of the Olfactory Bulb
    KRISTAL RAYLONE TUCKER; Fiscal Year: 2009
    ..With the ever increasing obese population in the United States, it will be important to understand how the chemistry of the obese state affects brain function. ..
  27. Behavioral Measures of Temporal Resolution in Mice With or Without Kv1.1 Subunits
    Micheal L Dent; Fiscal Year: 2010
    ..It is unknown, however, how this affects the 'real world'listening situation of these animals, so this will be determined here. ..
  28. Voltage-dependent activation in K+ channels
    Diane M Papazian; Fiscal Year: 2013
    ..An increase in the permeability of this barrier is a newly- discovered cause of human genetic diseases;the proposed research may lead to new therapeutic approaches to seal the barrier in these diseases. ..
  29. Neuropathogenesis of Immune Reconstitution Syndrome with HIV Infection
    Avindra Nath; Fiscal Year: 2010
    ..Specific aim 2: To determine the mechanism of GB mediated neurotoxicity Specific aim 3: To determine the mechanism of neuroprotection with Kv1.3 blockers ..
  30. K+ channel complexes: assembly, trafficking and function
    William R Kobertz; Fiscal Year: 2013
    ....
  31. Allostery and voltage sensing of membrane proteins
    Michael Priest; Fiscal Year: 2013
    ..As these membrane proteins are already successful targets for many therapies, improved understanding of how to modulate their function should lead towards improvements of human health. ..
  32. Structural Basis for KCNE Modulation of the KCNQ1 Channel
    Carlos G Vanoye; Fiscal Year: 2013
    ..Aim 5. Determine the structure of KCNE4 in bilayers and formulate a working model for how KCNE4 inhibits KCNQ1 channel function. ..
  33. Fear Modulation of IL excitability
    James T Porter; Fiscal Year: 2013
    ..A better understanding of the mechanisms leading to intrinsic plasticity in this brain structure may provide direction for the development of novel treatments for PTSD. ..
  34. Voltage-gated K channels, microglia and HIV Dementia
    HUANGUI HANK XIONG; Fiscal Year: 2010
    ..If successful, these studies will provide a proper roadmap for expected efficacy of Kv channel antagonists in ameliorating brain injury. ..
  35. The Microglial Kv1.3 Channel in Alzheimer's Disease
    Heike Wulff; Fiscal Year: 2012
    ..3 is important in microglia-caused damage. We will further test whether an inhibitor for Kv1.3 reduces microglia activity in an animal model of Alzheimer's disease. ..
  36. GENETIC STUDIES OF THE SYNAPSE
    Lily Y Jan; Fiscal Year: 2013
    ..Because the Kv1 voltage-gated potassium channels reside on both dendrites and axons, the mosaic analysis with double markers (MADM) approach will be employed to study the physiological role of dendritic Kv1 channels. ..
  37. SPERM PROGESTERONE RECEPTOR, K+ CHANNEL & PB EXPOSURE
    Asha Jacob; Fiscal Year: 1999
    ..They will determine the stage-specific expression of the human sperm K+ channel by in situ RT/PCR on human testes biopsy sections. ..
  38. Chronic ethanol-induced plasticity of NMDA and Kv4.2 is mediated by KChIP3
    Kathryn B Spencer; Fiscal Year: 2013
    ....
  39. A Mouse Model of Mammalian Shaker Channel RNA Editing
    Tarun Bhalla; Fiscal Year: 2006
    ..The studies outlined below aim to understand the functional consequences of RNA editing of Kv1.1 in the mammalian nervous system. ..
  40. Sigma Receptor Structure /Function /K+ Channel Modulation
    ARNOLD RUOHO; Fiscal Year: 2007
    ..4 potassium channels and other protein partners. These experiments will be performed through the combined use of photoactivatable molecules, electrophysiology, and recombinant and fusion proteins. ..
  41. GENETIC STUDIES OF THE SYNAPSE
    Lily Jan; Fiscal Year: 2000
    ....
  42. Structural Analysis of Voltage-gated Potassium Channels
    ROBERT BLAUSTEIN; Fiscal Year: 2006
    ..abstract_text> ..
  43. Development of Chemical Probes for KCNQ Potassium Channels
    Min Li; Fiscal Year: 2009
    ..This proposal is aimed at carrying out a screen of large compound library in an effort of finding novel chemical modulators for ion channels. ..
  44. Small Molecule Kv1.3 Blockers as New Therapeutics for Multiple Sclerosis
    Heike Wulff; Fiscal Year: 2007
    ..Lay: In multiple sclerosis the immune system attacks proteins in the brain of afflicted patients. The aim of this study is to identify and test new drugs that can suppress the white blood cells that are invading the brain. ..
  45. MOLECULAR DETERMINANTS OF POTASSIUM CHANNEL DRUG BLOCK
    Dirk Snyders; Fiscal Year: 2003
    ....
  46. Development of HTS Assays for Sub-Threshold Potassium Channels
    Timothy Jegla; Fiscal Year: 2006
    ..The research proposed in this application aims to develop a novel class of therapeutically relevant ion channel modulators in the hope that they will help patients that do not respond to current medications. ..
  47. FUNCTIONAL DOMAINS OF K+ CHANNEL SUBUNIT PROTEINS
    Paul Pfaffinger; Fiscal Year: 2004
    ..By completing these studies we will significantly extend our understanding of the structures of voltage-gated potassium channels, and their roles as part of the cell biology of excitable cells. ..
  48. Modulation of Voltage-gated K Channels in Glomus Cells
    Machiko Shirahata; Fiscal Year: 2006
    ..These diseases are known to have a genetic basis. ..
  49. REGULATORY MECHANISMS OF CARDIAC REPOLARIZATION
    Michael Tamkun; Fiscal Year: 2005
    ..Given the role that both Kv channels and connexins play in cardiac and vascular smooth muscle, the proposed research will significantly advance our understanding of electrical excitability in the cardiovascular system. ..
  50. MECHANISM OF REGULATION OF A GLOMERULAR K CHANNEL
    STEVEN SANSOM; Fiscal Year: 2005
    ..Ultimately, better management of some forms of hypertension could develop from an in-depth understanding of BK regulatory mechanism at the molecular level. ..
  51. ION CHANNELS AND PULMONARY VASCULAR TONE
    JASON YUAN; Fiscal Year: 1999
    ..These studies will provide insight into mechanisms responsible for the pathogenesis of pulmonary hypertension in chronic hypoxic pulmonary disease. ..
  52. INITIATION OF CELL DEATH BY POTASSIUM CHANNEL BLOCK
    Linda Iverson; Fiscal Year: 2004
    ....
  53. Role of Cerebrovascular K+ Channels in Hypertension
    NANCY RUSCH; Fiscal Year: 2005
    ..abstract_text> ..
  54. NOVEL T CELL ACTIVATION GENE IN DEVELOPING NEURONS
    Michael Prystowsky; Fiscal Year: 1999
    ..These studies will define the functional significance for KvBeta subunits in both the nervous and immune systems and begin to address molecular mechanisms regulating tissue specific expression. ..
  55. Targeting of Voltage-gated K+ Channels to Lipid Rafts
    Michael Tamkun; Fiscal Year: 2004
    ..1-containing lipid rafts from brain. This proposed research examines a new area in Kv channel research that will have important implications in multiple tissue systems. ..
  56. PURIFICATION OF BRAIN DENDROTOXIN RECEPTORS
    ROGER SORENSEN; Fiscal Year: 1990
    ..Additionally antibodies will be prepared against the purified receptor...
  57. DIFFERENTIATION OF NEURONAL SIGNALING MECHANISMS
    MICHAEL BARISH; Fiscal Year: 2000
    ....
  58. Characterization of the Sigma-1 Receptor
    DOMINIQUE FONTANILLA; Fiscal Year: 2009
    ..Elucidating the structure of the sigma-1 receptor and it's binding site will provide insight as to the functional role of the sigma-1 receptor as well as it's potential as a drug target. ..
  59. PULMONARY TYPE II EPITHELIAL CELLS--ROLE OF ION
    Elizabeth Jacobs; Fiscal Year: 1992
    ..The opportunity to advance both my career and knowledge about these mechanisms is made possible by close collaboration of the Departments of Medicine and Physiology in this institution...
  60. NOVEL ACCESSORY PROTEIN MODULATING CARDIAC K+ CHANNELS
    Barbara Wible; Fiscal Year: 2001
    ..Together these studies should provide valuable information on a novel mechanism of K+ channel regulation. ..
  61. CaMKII Regulation of Kv4.2 in the Hippocampus
    ANDREW VARGA; Fiscal Year: 2003
    ..2 phosphorylation that occur when hippocampal slices undergo long-term potentiation. Taken together, these data may provide a novel mechanism by which CaMKII affects memo formation. ..
  62. POTASSIUM HOMEOSTASTASIS OF KV 1.3-DEFICIENT MICE
    Jianchao Xu; Fiscal Year: 2005
    ..3 in renal epithelial cells. (2) Generation of Kv1.3-deficient mice. (3) Characterization of the K0.3-deficient mice. (4) Generation of KCNA10 knockout mouse and Kv1.3/KCNA10 double knockout mouse. ..
  63. Identification of targeting motifs in K+ channels
    Jacqueline Rivera; Fiscal Year: 2005
    ..2. and Aim 2). To identify the amino acid motif that is necessary and sufficient for axonal targeting of the Kv1.3 channel. ..
  64. K+ Channel Regulation/Cerebral Vascular Smooth Muscle
    LUIS SANTANA; Fiscal Year: 2007
    ..abstract_text> ..