potassium channels

Summary

Summary: Cell membrane glycoproteins that are selectively permeable to potassium ions. At least eight major groups of K channels exist and they are made up of dozens of different subunits.

Top Publications

  1. ncbi hERG potassium channels and cardiac arrhythmia
    Michael C Sanguinetti
    Department of Physiology, University of Utah, 95 South 2000 East, Salt Lake City, Utah 84112, USA
    Nature 440:463-9. 2006
  2. pmc Crystal structure of the human K2P TRAAK, a lipid- and mechano-sensitive K+ ion channel
    Stephen G Brohawn
    Laboratory of Molecular Neurobiology and Biophysics and Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA
    Science 335:436-41. 2012
  3. ncbi Mechanism of calcium gating in small-conductance calcium-activated potassium channels
    X M Xia
    Vollum Institute, Oregon Health Sciences University, Portland 97201, USA
    Nature 395:503-7. 1998
  4. ncbi Hyperpolarization-activated cation channels: from genes to function
    Martin Biel
    Center for Integrated Protein Science CIPS M and Zentrum für Pharmaforschung, Department Pharmazie, Pharmakologie für Naturwissenschaften, Ludwig Maximilians Universitat Munchen, Butenandtstr 5 13, Munich D 81377, Germany
    Physiol Rev 89:847-85. 2009
  5. 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
  6. pmc Structural mechanism of C-type inactivation in K(+) channels
    Luis G Cuello
    Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, University of Chicago, Illinois 60637, USA
    Nature 466:203-8. 2010
  7. ncbi Gated access to the pore of a voltage-dependent K+ channel
    Y Liu
    Department of Neurobiology, Harvard Medical School and Massachusetts General Hospital, Boston 02114, USA
    Neuron 19:175-84. 1997
  8. ncbi KATP channels as molecular sensors of cellular metabolism
    Colin G Nichols
    Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA
    Nature 440:470-6. 2006
  9. ncbi The structure of the potassium channel: molecular basis of K+ conduction and selectivity
    D A Doyle
    Laboratory of Molecular Neurobiology and Biophysics and the Howard Hughes Medical Institute, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Science 280:69-77. 1998
  10. 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

Detail Information

Publications371 found, 100 shown here

  1. ncbi hERG potassium channels and cardiac arrhythmia
    Michael C Sanguinetti
    Department of Physiology, University of Utah, 95 South 2000 East, Salt Lake City, Utah 84112, USA
    Nature 440:463-9. 2006
    hERG potassium channels are essential for normal electrical activity in the heart. Inherited mutations in the HERG gene cause long QT syndrome, a disorder that predisposes individuals to life-threatening arrhythmias...
  2. pmc Crystal structure of the human K2P TRAAK, a lipid- and mechano-sensitive K+ ion channel
    Stephen G Brohawn
    Laboratory of Molecular Neurobiology and Biophysics and Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA
    Science 335:436-41. 2012
    ..Two diagonally opposed gate-forming inner helices form membrane-interacting structures that may underlie this channel's sensitivity to chemical and mechanical properties of the cell membrane...
  3. ncbi Mechanism of calcium gating in small-conductance calcium-activated potassium channels
    X M Xia
    Vollum Institute, Oregon Health Sciences University, Portland 97201, USA
    Nature 395:503-7. 1998
    ..that follows an action potential is generated by the activation of small-conductance calcium-activated potassium channels (SK channels)...
  4. ncbi Hyperpolarization-activated cation channels: from genes to function
    Martin Biel
    Center for Integrated Protein Science CIPS M and Zentrum für Pharmaforschung, Department Pharmazie, Pharmakologie für Naturwissenschaften, Ludwig Maximilians Universitat Munchen, Butenandtstr 5 13, Munich D 81377, Germany
    Physiol Rev 89:847-85. 2009
    ..Finally, we provide an overview of the impact of HCN channels on the pathogenesis of several diseases and discuss recent attempts to establish HCN channels as drug targets...
  5. 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...
  6. pmc Structural mechanism of C-type inactivation in K(+) channels
    Luis G Cuello
    Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, University of Chicago, Illinois 60637, USA
    Nature 466:203-8. 2010
    ..These structures indicate a molecular basis for C-type inactivation in K(+) channels...
  7. ncbi Gated access to the pore of a voltage-dependent K+ channel
    Y Liu
    Department of Neurobiology, Harvard Medical School and Massachusetts General Hospital, Boston 02114, USA
    Neuron 19:175-84. 1997
    ..The results suggest that these channels open and close by the movement of an intracellular gate, distinct from the selectivity filter, that regulates access to the pore...
  8. ncbi KATP channels as molecular sensors of cellular metabolism
    Colin G Nichols
    Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA
    Nature 440:470-6. 2006
    ..In parallel, the uncovering of disease-causing mutations of K(ATP) has led to an explanation of the molecular basis of disease and, in turn, to a better understanding of the structural basis of channel function...
  9. ncbi The structure of the potassium channel: molecular basis of K+ conduction and selectivity
    D A Doyle
    Laboratory of Molecular Neurobiology and Biophysics and the Howard Hughes Medical Institute, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Science 280:69-77. 1998
    ..The architecture of the pore establishes the physical principles underlying selective K+ conduction...
  10. 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.
  11. pmc Structural basis for the coupling between activation and inactivation gates in K(+) channels
    Luis G Cuello
    Department of Biochemistry and Molecular Biology, The University of Chicago, 929 E 57th Street, Chicago, Illinois 60637, USA
    Nature 466:272-5. 2010
    ..We propose that side-chain rearrangements at position 103 mechanically couple activation and inactivation in KcsA and a variety of other K(+) channels...
  12. ncbi Molecular biology of adenosine triphosphate-sensitive potassium channels
    L Aguilar-Bryan
    Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA
    Endocr Rev 20:101-35. 1999
    KATP channels are a newly defined class of potassium channels based on the physical association of an ABC protein, the sulfonylurea receptor, and a K+ inward rectifier subunit...
  13. pmc A family of potassium channel genes related to eag in Drosophila and mammals
    J W Warmke
    Laboratory of Genetics, University of Wisconsin, Madison 53706
    Proc Natl Acad Sci U S A 91:3438-42. 1994
    ....
  14. ncbi Interactions between S4-S5 linker and S6 transmembrane domain modulate gating of HERG K+ channels
    Martin Tristani-Firouzi
    Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA
    J Biol Chem 277:18994-9000. 2002
    ..Moreover, our findings suggest that the C-terminal ends of S4 and S6 are in close proximity at hyperpolarized membrane potentials...
  15. ncbi Human hair follicles contain two forms of ATP-sensitive potassium channels, only one of which is sensitive to minoxidil
    Katie Shorter
    Department of Biomedical Sciences, University of Bradford, Bradford, BD7 1DP, UK
    FASEB J 22:1725-36. 2008
    ....
  16. ncbi HERG, a human inward rectifier in the voltage-gated potassium channel family
    M C Trudeau
    Department of Physiology, University of Wisconsin Medical School, Madison 53706, USA
    Science 269:92-5. 1995
    In contrast to other members of the Eag family of voltage-gated, outwardly rectifying potassium channels, the human eag-related gene (HERG) has now been shown to encode an inwardly rectifying potassium channel...
  17. pmc Two forms of electrical resonance at theta frequencies, generated by M-current, h-current and persistent Na+ current in rat hippocampal pyramidal cells
    Hua Hu
    Institute of Physiology, University of Oslo, PB 1103 Blindern, 0317 Oslo, Norway
    J Physiol 545:783-805. 2002
    ..These results suggest a novel function for M/KCNQ channels in the brain: to facilitate neuronal resonance and network oscillations in cortical neurons, thus providing a basis for an oscillation-based neural code...
  18. ncbi Structural basis for modulation and agonist specificity of HCN pacemaker channels
    William N Zagotta
    Department of Physiology and Biophysics, Howard Hughes Medical Institute, Box 357290, University of Washington School of Medicine, Seattle, Washington 98195 7290, USA
    Nature 425:200-5. 2003
    ..On the basis of amino acid sequence similarity to HCN channels, the cyclic nucleotide-gated, and eag- and KAT1-related families of channels are probably related to HCN channels in structure and mechanism...
  19. ncbi Dendritic hyperpolarization-activated currents modify the integrative properties of hippocampal CA1 pyramidal neurons
    J C Magee
    Neuroscience Center, Louisiana State University Medical Center, New Orleans, Louisiana 70112, USA
    J Neurosci 18:7613-24. 1998
    ..Overall, Ih acts to dampen dendritic excitability, but its largest impact is on the subthreshold range of membrane potentials where the integration of inhibitory and excitatory synaptic inputs takes place...
  20. 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...
  21. ncbi A dominant-negative mutation in the TRESK potassium channel is linked to familial migraine with aura
    Ronald G Lafreniere
    Centre of Excellence in Neuromics and Department of Medicine, Universite de Montreal, Centre Hospitalier de l Universite de Montreal, Research Centre, Notre Dame Hospital, Montreal, Quebec, Canada
    Nat Med 16:1157-60. 2010
    ..These results therefore support a role for TRESK in the pathogenesis of typical migraine with aura and further support the role of this channel as a potential therapeutic target...
  22. ncbi HCN channels: structure, cellular regulation and physiological function
    C Wahl-Schott
    Center for Integrated Protein Science CIPSM and Zentrum für Pharmaforschung, Department Pharmazie, Pharmakologie für Naturwissenschaften, Ludwig Maximilians Universitat Munchen, Butenandtstr 5 13, 81377 Munchen, Germany
    Cell Mol Life Sci 66:470-94. 2009
    ..In this review we give an overview on structure, function and regulation of HCN channels. Particular emphasis will be laid on the complex roles of these channels for neuronal function and cardiac rhythmicity...
  23. pmc The mitochondrial K(ATP) channel--fact or fiction?
    Keith D Garlid
    Department of Biology, Portland State University, Portland, OR 97201 0751, USA
    J Mol Cell Cardiol 52:578-83. 2012
    ..is the evidence for the presence of a K(ATP) channel in mitochondria? Are the pharmacological agents used to modulate mitoK(ATP) activity sufficiently specific to allow the role of these channels in cardioprotection to be established?..
  24. pmc Properties of ivabradine-induced block of HCN1 and HCN4 pacemaker channels
    A Bucchi
    Laboratory of Molecular Physiology and Neurobiology, Department of Biomolecular Sciences and Biotechnology, University of Milano, Italy
    J Physiol 572:335-46. 2006
    ..The mode of action of ivabradine on the two channels is discussed by implementing a simplified version of a previously developed model of f-channel kinetics...
  25. ncbi Multiple regulatory sites in large-conductance calcium-activated potassium channels
    Xiao Ming Xia
    Department of Anesthesiology, Washington University School of Medicine, Box 8054, St Louis, Missouri 63110, USA
    Nature 418:880-4. 2002
    ..This allows BK channels to serve a variety of physiological roles contingent on the Ca(2+) concentration to which the channels are exposed...
  26. ncbi Small-conductance, calcium-activated potassium channels from mammalian brain
    M Kohler
    Vollum Institute, L 474, Oregon Health Sciences University, 3181 Southwest Sam Jackson Road, Portland, OR 97201, USA J Maylie, Department of Obstetrics and Gyne
    Science 273:1709-14. 1996
    ..Expression of the messenger RNAs in Xenopus oocytes resulted in calcium-activated, voltage-independent potassium channels. The channels that formed from the various subunits displayed differential sensitivity to apamin and ..
  27. ncbi Hyperpolarization-activated cation currents: from molecules to physiological function
    Richard B Robinson
    Department of Pharmacology, Center for Molecular Therapeutics, Columbia University, New York, NY 10032, USA
    Annu Rev Physiol 65:453-80. 2003
    ..Moreover, we consider selected examples of the expanding physiological functions of Ih with a view toward understanding how the properties of HCN channels contribute to these diverse functional roles...
  28. ncbi Global twisting motion of single molecular KcsA potassium channel upon gating
    Hirofumi Shimizu
    CREST Sasaki team, Japan Science and Technology Corporation, Tachikawa, Tokyo, 190 0012, Japan
    Cell 132:67-78. 2008
    ..Crystal structures of several kinds of potassium channels have revealed open and closed conformations, which provide static pictures of gating status...
  29. pmc Mechanism of activation gating in the full-length KcsA K+ channel
    Serdar Uysal
    Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637, USA
    Proc Natl Acad Sci U S A 108:11896-9. 2011
    ..We suggest that by limiting the extent to which the inner gate can open, the cytoplasmic domain also modulates the level of inactivation occurring at the selectivity filter...
  30. 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...
  31. pmc A structural model for K2P potassium channels based on 23 pairs of interacting sites and continuum electrostatics
    Astrid Kollewe
    Institute for Molecular Pediatric Sciences, Department of Pediatrics, The University of Chicago, Pritzker School of Medicine, Chicago, IL 60637, USA
    J Gen Physiol 134:53-68. 2009
    ....
  32. pmc TREK-1, a K+ channel involved in neuroprotection and general anesthesia
    C Heurteaux
    Institut de Pharmacologie Moleculaire et Cellulaire, CNRS, Institut Paul Hamel, Sophia Antipolis, Valbonne, France
    EMBO J 23:2684-95. 2004
    ..Trek1-/- mice are also resistant to anesthesia by volatile anesthetics. TREK-1 emerges as a potential innovative target for developing new therapeutic agents for neurology and anesthesiology...
  33. ncbi A component of calcium-activated potassium channels encoded by the Drosophila slo locus
    N S Atkinson
    Laboratory of Genetics, University of Wisconsin, Madison 53706
    Science 253:551-5. 1991
    Calcium-activated potassium channels mediate many biologically important functions in electrically excitable cells...
  34. ncbi Cloning and functional characterization of novel large conductance calcium-activated potassium channel beta subunits, hKCNMB3 and hKCNMB4
    R Brenner
    Howard Hughes Medical Institute, Molecular and Cellular Physiology, Stanford School of Medicine, Stanford, California 94305, USA
    J Biol Chem 275:6453-61. 2000
    ..These results suggest that beta subunits in diverse tissue types fine-tune slo channel properties to the needs of a particular cell...
  35. ncbi Cns distribution of members of the two-pore-domain (KCNK) potassium channel family
    E M Talley
    Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908, USA
    J Neurosci 21:7491-505. 2001
    ..The differential expression of each of these genes likely contributes to characteristic excitability properties in distinct populations of neurons, as well as to diversity in their susceptibility to modulation...
  36. pmc Integrated allosteric model of voltage gating of HCN channels
    C Altomare
    Dipartimento di Fisiologia e Biochimica Generali, Via Celoria 26, , Via Celoria 16, 20133 Milano, Italy
    J Gen Physiol 117:519-32. 2001
    ..HCN voltage gating thus involves two processes: voltage sensor gating and allosteric opening/closing...
  37. ncbi Sequence and function of the two P domain potassium channels: implications of an emerging superfamily
    S A Goldstein
    Department of Pediatrics, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06536, USA
    J Mol Med (Berl) 76:13-20. 1998
    ..The two P domain K+ channels offer a new perspective from which to glimpse the molecular basis for function and dysfunction of K+-selective ion channels...
  38. ncbi Blocker protection in the pore of a voltage-gated K+ channel and its structural implications
    D del Camino
    Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 403:321-5. 2000
    ..of the bacterial potassium channel KcsA has provided a framework for understanding the related voltage-gated potassium channels (Kv channels) that are used for signalling in neurons...
  39. 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...
  40. 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
    ....
  41. pmc Properties of hyperpolarization-activated pacemaker current defined by coassembly of HCN1 and HCN2 subunits and basal modulation by cyclic nucleotide
    S Chen
    Department of Pharmacology, ColumbiaUniversity, New York, New York 10032, USA
    J Gen Physiol 117:491-504. 2001
    ..Finally, differences in Ih channel properties recorded in cell-free patches versus intact oocytes are shown to be due, in part, to modulation of Ih by basal levels of cAMP in intact cells...
  42. ncbi Energy-efficient action potentials in hippocampal mossy fibers
    Henrik Alle
    Independent Hertie Research Group, Max Planck Institute for Brain Research, 60528 Frankfurt, Germany
    Science 325:1405-8. 2009
    ..Analysis of ionic conductance parameters revealed that the properties of Na+ and K+ channels are matched to make axonal action potentials energy-efficient, minimizing their contribution to activity-dependent metabolism...
  43. ncbi Molecular and functional heterogeneity of hyperpolarization-activated pacemaker channels in the mouse CNS
    B Santoro
    Center for Neurobiology and Behavior, Departments of Pharmacology and Anesthesiology, and Howard Hughes Medical Institute, Columbia University, New York, New York 10032, USA
    J Neurosci 20:5264-75. 2000
    ..Moreover, in some neurons, specific functional roles can be proposed for I(h) channels with defined subunit composition...
  44. ncbi DPP10 modulates Kv4-mediated A-type potassium channels
    Edward Zagha
    Department of Physiology and Neuroscience, New York University School of Medicine, New York, New York 10016
    J Biol Chem 280:18853-61. 2005
    ..homologous to subfamily member DPPX, which we previously reported as a modulator of Kv4-mediated A-type potassium channels (Nadal, M. S., Ozaita, A., Amarillo, Y., Vega-Saenz de Miera, E., Ma, Y., Mo, W., Goldberg, E. M., Misumi, Y...
  45. ncbi Energetics of ion conduction through the K+ channel
    S Berneche
    Department of Biochemistry, Weill Medical College of Cornell University, New York, New York 10021, USA
    Nature 414:73-7. 2001
    ..Ion-ion repulsion, although essential for rapid conduction, is shown to act only at very short distances. The calculations show also that the rapidly conducting pore is selective...
  46. ncbi Chemistry of ion coordination and hydration revealed by a K+ channel-Fab complex at 2.0 A resolution
    Y Zhou
    Department of Molecular Biophysics and Biochemistry, Yale University, 260 Whitney Avenue, New Haven, Connecticut 06520, USA
    Nature 414:43-8. 2001
    ..This structural change is crucial to the operation of the selectivity filter in the cellular context, where the K+ ion concentration near the selectivity filter varies in response to channel gating...
  47. pmc On the selective ion binding hypothesis for potassium channels
    Ilsoo Kim
    Department of Chemistry, University of California, One Shields Avenue, Davis, CA 95616, USA
    Proc Natl Acad Sci U S A 108:17963-8. 2011
    ....
  48. ncbi TRESK: the lone ranger of two-pore domain potassium channels
    Peter Enyedi
    Department of Physiology, Semmelweis University, Budapest, Hungary
    Mol Cell Endocrinol 353:75-81. 2012
    ....
  49. pmc Tarantula toxins interacting with voltage sensors in potassium channels
    Kenton J Swartz
    Molecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
    Toxicon 49:213-30. 2007
    ..The conservation of tarantula toxin receptors among voltage-activated ion channels will also be discussed...
  50. pmc The S4-S5 linker couples voltage sensing and activation of pacemaker channels
    J Chen
    Department of Medicine, Division of Cardiology, Eccles Program in Human Molecular Biology and Genetics, University of Utah, Eccles Institute of Human Genetics, 15 N 2030 E, Room 4220, Salt Lake City, UT 84112, USA
    Proc Natl Acad Sci U S A 98:11277-82. 2001
    ..Our findings also suggest that opening of HCN and related channels corresponds to activation of a gate located near the inner pore, rather than recovery of channels from a C-type inactivated state...
  51. ncbi Ion conduction pore is conserved among potassium channels
    Z Lu
    Department of Physiology, University of Pennsylvania, Philadelphia 19104, USA
    Nature 413:809-13. 2001
    b>Potassium channels, a group of specialized membrane proteins, enable K+ ions to flow selectively across cell membranes. Transmembrane K+ currents underlie electrical signalling in neurons and other excitable cells...
  52. ncbi Molecular identification of a hyperpolarization-activated channel in sea urchin sperm
    R Gauss
    Institut für Biologische Informationsverarbeitung, Forschungszentrum Julich, Germany
    Nature 393:583-7. 1998
    ..Because of their sequence and functional properties, Ih channels form a class of their own within the superfamily of voltage-gated and cyclic-nucleotide-gated channels...
  53. pmc TRIP8b splice variants form a family of auxiliary subunits that regulate gating and trafficking of HCN channels in the brain
    Bina Santoro
    Department of Neuroscience, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA
    Neuron 62:802-13. 2009
    ..TRIP8b thus functions as an auxiliary subunit that provides a mechanism for the dynamic regulation of HCN1 channel expression and function...
  54. pmc Potassium channels as a potential therapeutic target for trigeminal neuropathic and inflammatory pain
    Mamoru Takeda
    Department of Physiology, School of Life Dentistry at Tokyo, Nippon Dental University, 1 9 20 Fujimi cho, Chiyoda ku, Tokyo, Japan
    Mol Pain 7:5. 2011
    ..We also discuss the potential of Kv channel openers as therapeutic agents for trigeminal neuropathic/inflammatory pain, such as mechanical allodynia...
  55. pmc Crystal structure of full-length KcsA in its closed conformation
    Serdar Uysal
    Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637, USA
    Proc Natl Acad Sci U S A 106:6644-9. 2009
    ..Functional analysis of the full-length KcsA-Fab complex suggests that the C-terminal bundle remains whole during gating. We suggest that this structure likely represents the physiologically relevant closed conformation of KcsA...
  56. ncbi TREK-2 (K2P10.1) and TRESK (K2P18.1) are major background K+ channels in dorsal root ganglion neurons
    Dawon Kang
    Department of Physiology and Biophysics, Rosalind Franklin University of Medicine and Science, Chicago Medical School, 3333 Green Bay Road, North Chicago, IL 60064, USA
    Am J Physiol Cell Physiol 291:C138-46. 2006
    ..As TREKs and TRESK are targets of modulation by receptor agonists, they are likely to play an active role in the regulation of excitability in DRG neurons...
  57. ncbi The size of gating charge in wild-type and mutant Shaker potassium channels
    N E Schoppa
    Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06510
    Science 255:1712-5. 1992
    ..A more direct measurement of q in Drosophila melanogaster Shaker 29-4 potassium channels yields a q value of 12.3 e0...
  58. ncbi Truncation of Kir6.2 produces ATP-sensitive K+ channels in the absence of the sulphonylurea receptor
    S J Tucker
    University Laboratory of Physiology, Oxford, UK
    Nature 387:179-83. 1997
    ATP-sensitive potassium channels (K-ATP channels) couple cell metabolism to electrical activity and are important in the physiology and pathophysiology of many tissues...
  59. ncbi Control of ion selectivity in potassium channels by electrostatic and dynamic properties of carbonyl ligands
    Sergei Yu Noskov
    Department of Biochemistry and Structural Biology, Weill Medical College of Cornell University, 1300 York Avenue, New York, New York 10021, USA
    Nature 431:830-4. 2004
    b>Potassium channels are essential for maintaining a normal ionic balance across cell membranes...
  60. ncbi Identification and properties of a novel intracellular (mitochondrial) ATP-sensitive potassium channel in brain
    R Bajgar
    Department of Biochemistry and Molecular Biology, OGI School of Science and Engineering, Oregon Health and Science University, Beaverton, Oregon 97006-8921, USA
    J Biol Chem 276:33369-74. 2001
    ..Three independent methods indicate that brain mitochondria contain six to seven times more mitoK(ATP) per milligram of mitochondrial protein than liver or heart...
  61. ncbi HCN2 ion channels play a central role in inflammatory and neuropathic pain
    Edward C Emery
    Department of Pharmacology, University of Cambridge, Cambridge CB2 1PD, UK
    Science 333:1462-6. 2011
    ..After a nerve lesion, these mice showed no neuropathic pain in response to thermal or mechanical stimuli. Neuropathic pain is therefore initiated by HCN2-driven action potential firing in Na(V)1.8-expressing nociceptors...
  62. pmc K+ channels as targets for specific immunomodulation
    K George Chandy
    Department of Physiology and Biophysics, University of California, Irvine, CA 92697, USA
    Trends Pharmacol Sci 25:280-9. 2004
    ..3 and IKCa1 channels, and provide a rationale for the potential therapeutic use of these inhibitors in immunological disorders...
  63. ncbi Distribution analysis of human two pore domain potassium channels in tissues of the central nervous system and periphery
    A D Medhurst
    Neuroscience Research, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Essex CM19 5AW, Harlow, UK
    Brain Res Mol Brain Res 86:101-14. 2001
    b>Potassium channels are amongst the most heterogeneous class of ion channels known and are responsible for mediating a diverse range of biological functions...
  64. ncbi Triggering and amplifying pathways of regulation of insulin secretion by glucose
    J C Henquin
    Unité d Endocrinologie et Métabolisme, University of Louvain Faculty of Medicine, Brussels, Belgium
    Diabetes 49:1751-60. 2000
    ..Besides the available drugs that act on K(ATP) channels and increase the triggering signal, novel drugs that correct a deficient amplifying pathway would be useful to restore adequate insulin secretion in type 2 diabetic patients...
  65. ncbi Restoration of inactivation in mutants of Shaker potassium channels by a peptide derived from ShB
    W N Zagotta
    Department of Molecular and Cellular Physiology, Stanford University School of Medicine, CA 94305
    Science 250:568-71. 1990
    Site-directed mutagenesis experiments have suggested a model for the inactivation mechanism of Shaker potassium channels from Drosophila melanogaster...
  66. pmc TRESK two-pore-domain K+ channels constitute a significant component of background potassium currents in murine dorsal root ganglion neurones
    Tina Dobler
    Institute of Physiology, University of Wurzburg, Röntgenring 9, 97070 Wurzburg, Germany
    J Physiol 585:867-79. 2007
    ..Most strikingly, cellular excitability of DRG neurones from functional KO mice was significantly augmented as revealed by reduced rheobase current to elicit action potentials...
  67. ncbi Long QT syndrome-associated mutations in the Per-Arnt-Sim (PAS) domain of HERG potassium channels accelerate channel deactivation
    J Chen
    Department of Medicine, Division of Cardiology, University of Utah, Salt Lake City, Utah 84112, USA
    J Biol Chem 274:10113-8. 1999
    ..The location of these mutations suggests they may disrupt the PAS domain and interfere with its interaction with the S4-S5 linker of the HERG channel...
  68. ncbi Voltage sensor of Kv1.2: structural basis of electromechanical coupling
    Stephen B Long
    Howard Hughes Medical Institute, Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Science 309:903-8. 2005
    ..The structure offers a simple picture of how membrane voltage influences the open probability of the channel...
  69. ncbi mSlo, a complex mouse gene encoding "maxi" calcium-activated potassium channels
    A Butler
    Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, MO 63110
    Science 261:221-4. 1993
    Complementary DNAs (cDNAs) from mSlo, a gene encoding calcium-activated potassium channels, were isolated from mouse brain and skeletal muscle, sequenced, and expressed in Xenopus oocytes...
  70. ncbi Potassium leak channels and the KCNK family of two-P-domain subunits
    S A Goldstein
    Department of Pediatrics and Cellular and Molecular Physiology, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06536, USA
    Nat Rev Neurosci 2:175-84. 2001
    With a bang, a new family of potassium channels has exploded into view. Although KCNK channels were discovered only five years ago, they already outnumber other channel types...
  71. pmc Salt bridges and gating in the COOH-terminal region of HCN2 and CNGA1 channels
    Kimberley B Craven
    Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195 7290, USA
    J Gen Physiol 124:663-77. 2004
    ..Discovering that one portion of the COOH terminus, the CNBD, can be in the activated configuration while the other portion, the C-linker, is not activated has lead us to suggest a novel modular gating scheme for HCN and CNG channels...
  72. ncbi Molecular cloning and characterization of the intermediate-conductance Ca(2+)-activated K(+) channel in vascular smooth muscle: relationship between K(Ca) channel diversity and smooth muscle cell function
    C B Neylon
    Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA
    Circ Res 85:e33-43. 1999
    ..The differential expression of these K(Ca) channels in functionally distinct smooth muscle cell types suggests that K(Ca) channels play a role in defining the physiological properties of vascular smooth muscle...
  73. 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...
  74. ncbi KCNQ/M currents in sensory neurons: significance for pain therapy
    Gayle M Passmore
    Department of Pharmacology, University College London, London WC1E 6BT, United Kingdom
    J Neurosci 23:7227-36. 2003
    ..It is suggested that IK(M) plays a key role in controlling the excitability of nociceptors and may represent a novel analgesic target...
  75. ncbi The local differentiation of myelinated axons at nodes of Ranvier
    Sebastian Poliak
    Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, Israel
    Nat Rev Neurosci 4:968-80. 2003
    ..This local differentiation of myelinated axons is tightly regulated by oligodendrocytes and myelinating Schwann cells, and is achieved through complex mechanisms that are used by another specialized cell-cell contact - the synapse...
  76. ncbi Molecular diversity of K+ channels
    W A Coetzee
    Department of Physiology, New York University School of Medicine, New York 10016, USA
    Ann N Y Acad Sci 868:233-85. 1999
    ....
  77. ncbi Theta-frequency bursting and resonance in cerebellar granule cells: experimental evidence and modeling of a slow k+-dependent mechanism
    E D'Angelo
    Department of Molecular Cellular Physiology and Instituto Nazionale per la Fisica della Materia, University of Pavia, I 27100 Pavia, Italy
    J Neurosci 21:759-70. 2001
    ..Theta-frequency bursting and resonance in granule cells may play an important role in determining synchronization, rhythmicity, and learning in the cerebellum...
  78. ncbi A unified nomenclature for short-chain peptides isolated from scorpion venoms: alpha-KTx molecular subfamilies
    J Tytgat
    Laboratory of Toxicology, University of Leuven, E Van Evenstraat 4, 3000 Leuven, Belgium
    Trends Pharmacol Sci 20:444-7. 1999
    ..Because of the pharmacological divergence of these peptides, the principle of classification was based on a primary sequence alignment, combined with maximum parsimony and Neighbour-Joining analysis...
  79. ncbi Molecular and functional properties of two-pore-domain potassium channels
    F Lesage
    Institut de Pharmacologie Moléculaire, et Cellulaire, Centre National de la Recherche Scientifique Unité Propre de Recherche 411, Sophia Antipolis, 06560 Valbonne, France
    Am J Physiol Renal Physiol 279:F793-801. 2000
    ....
  80. ncbi A family of hyperpolarization-activated mammalian cation channels
    A Ludwig
    Institut fur Pharmakologie und Toxikologie, Technische Universitat Munchen, Germany
    Nature 393:587-91. 1998
    ..We have also identified full-length sequences of two related channels, HAC2 and HAC3, that are specifically expressed in the brain, indicating the existence of a family of hyperpolarization-activated cation channels...
  81. ncbi Dichloroacetate, a metabolic modulator, prevents and reverses chronic hypoxic pulmonary hypertension in rats: role of increased expression and activity of voltage-gated potassium channels
    Evangelos D Michelakis
    Department of Medicine, University of Alberta, Edmonton, Canada
    Circulation 105:244-50. 2002
    ..We hypothesized that dichloroacetate (DCA), a metabolic modulator that can shift redox balance toward an oxidized state and increase Kv current in myocardial cells, would reverse CH-PHT...
  82. pmc Mutations in the K+ channel signature sequence
    L Heginbotham
    Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115
    Biophys J 66:1061-7. 1994
    b>Potassium channels share a highly conserved stretch of eight amino acids, a K+ channel signature sequence. The conserved sequence falls within the previously defined P-region of voltage-activated K+ channels...
  83. ncbi ATP-sensitive K+ channel-dependent regulation of glucagon release and electrical activity by glucose in wild-type and SUR1-/- mouse alpha-cells
    Jesper Gromada
    Lilly Research Laboratories, Essener Strasse 93, D 22419 Hamburg, Germany
    Diabetes 53:S181-9. 2004
    ....
  84. ncbi A behavioral role for dendritic integration: HCN1 channels constrain spatial memory and plasticity at inputs to distal dendrites of CA1 pyramidal neurons
    Matthew F Nolan
    Center for Neurobiology and Behavior, Columbia University, New York, NY 10032, USA
    Cell 119:719-32. 2004
    ..We suggest that HCN1 channels constrain learning and memory by regulating dendritic integration of distal synaptic inputs to pyramidal cells...
  85. pmc Molecular regulations governing TREK and TRAAK channel functions
    Jacques Noel
    Universite de Nice Sophia Antipolis, UFR Sciences, Nice, France
    Channels (Austin) 5:402-9. 2011
    ..Molecular heterogeneity, regulatory mechanisms and protein partners are all expected to contribute to cell specific functions of TREK currents in many tissues...
  86. pmc Filter gate closure inhibits ion but not water transport through potassium channels
    Torben Hoomann
    Institute of Biophysics, Johannes Kepler University of Linz, 4020 Linz, Austria
    Proc Natl Acad Sci U S A 110:10842-7. 2013
    ..This questions the widely accepted hypothesis that multiple K(+) ions in the selectivity filter act to mutually destabilize binding. ..
  87. ncbi KCTD5, a putative substrate adaptor for cullin3 ubiquitin ligases
    Yolanda Bayon
    Instituto de Biologia y Genetica Molecular, CSIC Universidad de Valladolid, Spain
    FEBS J 275:3900-10. 2008
    ..and broad complex (BTB) domain that is most similar to the tetramerization domain (T1) of voltage-gated potassium channels. Some BTB-domain-containing proteins have been shown recently to participate as substrate-specific adaptors ..
  88. pmc The mechano-activated K+ channels TRAAK and TREK-1 control both warm and cold perception
    Jacques Noel
    Universite de Nice Sophia Antipolis, CNRS UMR6097, Institut de Pharmacologie Moleculaire et Cellulaire, Institut Paul Hamel, Sophia Antipolis, Valbonne, France
    EMBO J 28:1308-18. 2009
    ..However, we show here that the mechano-gated and highly temperature-sensitive potassium channels of the TREK/TRAAK family, which normally work as silencers of the excitatory channels, are also implicated...
  89. pmc Potassium channels in articular chondrocytes
    Ali Mobasheri
    Musculoskeletal Research Group, Division of Veterinary Medicine, Faculty of Medicine and Health Sciences, The University of Nottingham, Sutton Bonington Campus, Sutton Bonington, Leicestershire, UK ali
    Channels (Austin) 6:416-25. 2012
    ..The range of known potassium channels expressed by these unique cells is continually increasing...
  90. pmc The role of mitochondria in protection of the heart by preconditioning
    Andrew P Halestrap
    Department of Biochemistry and Bristol Heart Institute, University of Bristol, School of Medical Sciences, University Walk, Bristol BS8 1TD, UK
    Biochim Biophys Acta 1767:1007-31. 2007
    ..including the potential roles for reactive oxygen species (ROS), protein kinase cascades, and mitochondrial potassium channels. It is proposed that IP-mediated inhibition of MPTP opening at reperfusion does not involve direct ..
  91. ncbi Mutant potassium channels with altered binding of charybdotoxin, a pore-blocking peptide inhibitor
    R MacKinnon
    Howard Hughes Medical Institute, Brandeis University, Waltham, MA 02254
    Science 245:1382-5. 1989
    The inhibition by charybdotoxin of A-type potassium channels expressed in Xenopus oocytes was studied for several splicing variants of the Drosophila Shaker gene and for several site-directed mutants of this channel...
  92. ncbi Preconditioning with isoflurane produces dose-dependent neuroprotection via activation of adenosine triphosphate-regulated potassium channels after focal cerebral ischemia in rats
    Lize Xiong
    Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi an, Shaanxi, China
    Anesth Analg 96:233-7, table of contents. 2003
    ..ischemia in a dose-response manner and whether the effect is dependent on adenosine triphosphate-regulated potassium channels. In Experiment 1, 40 rats were randomly assigned to 4 groups: control animals received 100% oxygen 1 h/d for ..
  93. ncbi Molecular organization of the cullin E3 ligase adaptor KCTD11
    Stefania Correale
    Institute of Biostructures and Bioimaging, CNR, Napoli, Italy
    Biochimie 93:715-24. 2011
    ..Moreover, these models provide insights into the determinants of the tetramer stability and into the regions involved in lKCTD11-Cul3 recognition...
  94. ncbi Energetic optimization of ion conduction rate by the K+ selectivity filter
    J H Morais-Cabral
    Department of Molecular Biophysics and Biochemistry, Yale University, 260 Whitney Avenue, New Haven, Connecticut 06520, USA
    Nature 414:37-42. 2001
    ..The energetic balance between these configurations is a clear example of evolutionary optimization of protein function...
  95. ncbi Two types of inactivation in Shaker K+ channels: effects of alterations in the carboxy-terminal region
    T Hoshi
    Department of Molecular and Cellular Physiology, Stanford University School of Medicine, California 94305
    Neuron 7:547-56. 1991
    Shaker potassium channels inactivate and recover from inactivation with multiple exponential components, suggesting the presence of multiple inactivation processes...
  96. ncbi Potassium channels in plant cells
    Ingo Dreyer
    Centro de Biotecnología y Genómica de Plantas, Universidad Politecnica de Madrid, Madrid, Spain
    FEBS J 278:4293-303. 2011
    ..An essential role in potassium uptake and efflux is played by potassium channels. Since the first molecular characterization of K(+) channels from Arabidopsis thaliana in 1992, a large ..
  97. ncbi Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion
    L Aguilar-Bryan
    Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA
    Science 268:423-6. 1995
    ..The results suggest that the sulfonylurea receptor may sense changes in ATP and ADP concentration, affect KATP channel activity, and thereby modulate insulin release...
  98. ncbi Intracellular gate opening in Shaker K+ channels defined by high-affinity metal bridges
    Sarah M Webster
    Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nature 428:864-8. 2004
    Voltage-gated potassium channels such as Shaker help to control electrical signalling in neurons by regulating the passage of K+ across cell membranes...
  99. ncbi Immunohistochemical localization of Ih channel subunits, HCN1-4, in the rat brain
    Takuya Notomi
    Division of Cerebral Structure, National Institute for Physiological Sciences, Myodaiji, Okazaki 444 8585, Japan
    J Comp Neurol 471:241-76. 2004
    ..These results support previous electrophysiological findings and further suggest unexpected roles of I(h) channels in the brain...
  100. pmc HCN hyperpolarization-activated cation channels inhibit EPSPs by interactions with M-type K(+) channels
    Meena S George
    Department of Neuroscience, Columbia University, New York, New York, USA
    Nat Neurosci 12:577-84. 2009
    ..In this manner, I(h) can enhance spike firing in response to an EPSP when spike threshold is low and can inhibit firing when spike threshold is high...
  101. ncbi Pharmacological preconditioning in type 2 diabetic rat hearts: the roles of mitochondrial ATP-sensitive potassium channels and the phosphatidylinositol 3-kinase-Akt pathway
    Shuhei Matsumoto
    Department of Anesthesiology, Nagasaki University School of Medicine, Nagasaki, 852 8501, Japan
    Cardiovasc Drugs Ther 23:263-70. 2009
    ....

Research Grants75

  1. Principles of Therapy in Cerebellar Disease: Explorations in Ion Channel Mutants
    JOHN SAMUEL STAHL; Fiscal Year: 2013
    ..however, suggest that highly effective drugs can be developed: Two drugs that influence neuronal potassium channels have been shown to ameliorate cerebellar deficits in humans and mice, and may provide starting points to ..
  2. Structural and molecular basis of drug-induced IKACh reduction
    SAMI FOUAD NOUJAIM; Fiscal Year: 2013
    ..abstract_text> ..
  3. Structural and molecular basis of drug-induced IKACh reduction
    SAMI FOUAD NOUJAIM; Fiscal Year: 2012
    ..abstract_text> ..
  4. Parvalbumin-Containing Neurons in Schizophrenia
    Tsung Ung W Woo; Fiscal Year: 2013
    ..neuronal dysfunction via at least two mechanisms: oxidative stress and decreased expression of voltage-gated potassium channels Kv3.1b and Kv3.2, which play a critical role in conferring the fast-spiking properties to PV neurons...
  5. 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. ..
  6. K-Channels in Lymphocyte Function and Autoimmunity
    GEORGE KANIANTHARA CHANDY; Fiscal Year: 2012
    ..Our strategy is to selectively target voltage-gated Kv1.3 potassium channels in effector memory T cells that are important mediators of autoimmune diseases.
  7. Mechanism and functional role of AKAP79/150 in M current control and excitability
    Mark S Shapiro; Fiscal Year: 2010
    ..The elucidation of the mechanisms and functional role of AKAP79/150 in M-channel activity will shed light on how the nervous system functions in health and disease. ..
  8. Optimization of KCa2 Channel Activators as Neuroscience Tools and Potential Drugs
    Heike Wulff; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Small-conductance calcium activated potassium channels are encoded by the KCa2.1-2...
  9. New Peptides for the Treatment of Multiple Sclerosis
    Christine Beeton; Fiscal Year: 2013
    ..3 channels creates a high risk of toxicity through interactions with other potassium channels. We have developed a first generation of synthetic analogs of ShK by modifying its N-terminus with non-..
  10. Redox Regulation of Kv Channels
    SRINIVAS TIPPARAJU; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Voltage-gated potassium channels (Kv) maintain the resting membrane potential and the shape of the action potential...
  11. Endothelial SK3 Channel Modulation of EDHF is Estrogen Regulated
    Mike T Lin; Fiscal Year: 2011
    ..This proposal is designed to test the hypothesis that estrogen regulates endothelial potassium channels to modulate vascular reactivity and blood pressure.)
  12. Epigenetic modulation of epileptogenesis.
    PEYMAN GOLSHANI; Fiscal Year: 2010
    ....
  13. SK channels: Roles and mechanisms for dendritic excitability and plasticity
    James G Maylie; Fiscal Year: 2012
    ..PUBLIC HEALTH RELEVANCE: Neurons express a family of calcium-activated potassium channels (SK channels) that are implicated in the molecular and cellular mechanisms underlying learning and memory...
  14. Determinants of developing efferent synapses in the mammalian cochlea
    ISABELLE CATHERINA ROUX; Fiscal Year: 2013
    ..acetylcholine receptors (nAChRs) and is inhibitory due to the subsequent activation of calcium-dependent potassium channels. In the mature cochlea, efferent inputs modulate OHCs activity, thereby significantly influencing ..
  15. Physiology and Biophysics of Cardiac Slo2.1 Channels
    Alexey V Zaitsev; Fiscal Year: 2012
    ..These electrical gradients are highly relevant to the outcomes of cardiac defibrillation and resuscitation of individuals who have experienced sudden cardiac arrest. ..
  16. Intraocular pressure regulation via ATP-sensitive potassium channels
    Michael F Romero; Fiscal Year: 2013
    ..abstract_text> ..
  17. HEMOPROTEIN OXIDATION AND HEME CATABOLISM
    Paul R Ortiz de Montellano; Fiscal Year: 2013
    ..4. Define the interactions of HO-1 and HO-2 with naturally occurring polymorphic cytochrome P450 reductase (CPR) variants associated with human disease. ..
  18. Hydrogen Peroxide and Flow-Induced Dilation of Human Coronary Microcirculation
    David D Gutterman; Fiscal Year: 2012
    ..The direct relevance to humans with chronic coronary disease provides a strong foundation for this mechanistic approach to understanding microvascular reactivity. ..
  19. The microglial potassium channels Kv1.3 and KCa3.1 as therapeutic targets for neu
    Heike Wulff; Fiscal Year: 2013
    ..As a first step towards translating our findings to humans, we will further obtain brain sections from stroke patients and controls and perform immunohistochemistry for KCa3.1, Kv1.3, and microglia activation markers. ..
  20. MYOCARDIAL PERFUSION IN THE HYPERTROPHIED HEART
    ROBERT JAMES BACHE; Fiscal Year: 2010
    ..These studies will characterize responses of myocardial KATP channels that may contribute to the development of CHF in the chronically overloaded heart. ..
  21. Embryonic regulation of GnRH neuron migration and function
    David J Kozlowski; Fiscal Year: 2012
    ..A further understanding of the mechanisms guiding GnRH neuron migration is essential to determine the etiology of birth defects and predict clinical outcomes regarding reproductive maturation and fertility in humans. ..
  22. Role of Astrocytic TREK-2 Potassium Channels in Cerebral Ischemia
    Misty J Eaton; Fiscal Year: 2013
    ..b>Potassium channels in astrocytes are predominantly responsible for maintaining the hyperpolarized membrane potential of ..
  23. Excitability mechanisms of neurocardiac regulation
    ALBERT E GLASSCOCK; Fiscal Year: 2012
    ....
  24. Pharmacology of Intravesical Antisense Based Therapy for Over Active Bladder
    Naoki Yoshimura; Fiscal Year: 2013
    ..we will also test the hypothesis of OAB pathology triggered by changes in voltage- gated sodium and potassium channels, increased cytokines expression/release as well as muscarinic receptors, and such changes are mediated by ..
  25. Molecular mechanisms of auditory nAChR synapse assembly
    Michele H Jacob; Fiscal Year: 2013
    ..functional coupling and close positioning of [unreadable]9/10-nAChRs to small conductance calcium activated potassium channels (SK2)...
  26. Mitochondrial Kv1.3 potassium channels and lymphocyte apoptosis in sepsis
    Jay Yang; Fiscal Year: 2011
    ..The key role of plasma membrane Kv1.3 potassium channels in the activation of T lymphocytes has been recognized for some time...
  27. Satellite Glial Cells
    Luc Jasmin; Fiscal Year: 2013
    ..A better understanding of this glia-induced hyper-excitability is likely to open the door to new therapies for nerve-injured patients. ..
  28. Skeletal muscle ATP-sensitive potassium channels determine bodily energy balance
    Leonid Zingman; Fiscal Year: 2013
    ..Understanding these mechanisms will provide novel avenues for targeted management and prevention of obesity and related disease and future translational research. ..
  29. STRUCTURAL STUDIES ON PROKARYOTIC POTASSIUM CHANNELS
    Adrian Gross; Fiscal Year: 2013
    ..b>Potassium channels are the phylogenetic founders of a large superfamily of structurally related ion channels that includes ..
  30. Functions of 5'NCRs of picornavirus and cellular mRNAs
    Bert L Semler; Fiscal Year: 2013
    ..abstract_text> ..
  31. Epigenetic Regulation of Kir4.1 and GLT1 in Pathophysiology
    Michelle L Olsen; Fiscal Year: 2013
    ..Results from these experiments could lead to novel therapeutic strategies using FDA-approved drugs for the treatment of TBI in pediatric patients. ..
  32. Molecular mechanisms of potassium channel permeation and gating
    Crina M Nimigean; Fiscal Year: 2013
    ..Our first major aim is to understand aspects of permeation in potassium channels. Aim 1...
  33. Voltage-Gating in Bacterial Ion Channels
    Ana M Correa; Fiscal Year: 2010
    ....
  34. MODULATION OF OLFACTORY BULB NEURON CURRENT PROPERTIES
    Debra Ann Fadool; Fiscal Year: 2013
    ..3 increases olfactory ability and induces resistance to weight gain, holds great translational promise as a target for increasing odor discrimination or lessening imbalance in energy homeostasis (obesity). ..
  35. Functional immuno-imaging of lymphocyte motility and cell interactions in lymph n
    Michael D Cahalan; Fiscal Year: 2013
    ..The second goal is to investigate immunosuppression mediated by blockade of specific ion channels in T lymphocytes - a potassium channel Kv1.3 and a calcium channel Orai1 - for treatment of autoimmune disorders. ..
  36. 2-pore-domain K+ channels as novel targets for modulating islet hormone secretion
    DAVID AARON JACOBSON; Fiscal Year: 2013
    ....
  37. AT2 Receptors in the RVLM: Regulation of Sympathetic Outflow in Heart Failure
    Lie Gao; Fiscal Year: 2013
    ..They will highlight the importance of a balance between AT1 and AT2 receptor signaling in setting the level of sympatho-excitation and identify possible new targets for therapy in CHF. ..
  38. Volatile Anesthetic Regulation of TASK Tandem Pore Potassium Channels
    Joseph F Cotten; Fiscal Year: 2012
    ..PUBLIC HEALTH RELEVANCE This work will help establish principles to guide development of safer anesthetic drugs that do not effect breathing and further elucidate the mechanism by which these drugs induce anesthesia. ..
  39. Regulation of Renal Maxi K Channel by WNK Kinase
    Hui Cai; Fiscal Year: 2013
    ....
  40. The Role of the Calcium Activated Potassium Channel, KCa3.1, in the Pathogenesis
    Edward Skolnik; Fiscal Year: 2010
    ..1) already exists and are in human trials without any major side effects. Thus, if inhibiting this channel shows promise in mouse models of ADPKD, we can rapidly move into the clinic to assess treatment in patients. ..
  41. PPARy and Uterine Vascular Dysfunction in Diabetic Pregnancy
    Natalia I Gokina; Fiscal Year: 2011
    ..of Ca2+ signaling leading to decreased production of NO and diminished stimulation of Ca2+-activated potassium channels (SKCa and IKCa) (Specific Aim 1)...
  42. Opioid tolerance and bowel dysfunction
    William L Dewey; Fiscal Year: 2013
    ..tested to determine morphine- induced changes in electrical excitability and effects on sodium, calcium and potassium channels in wild-type and ? arrestin2 knock-out mice...
  43. Stimulus processing in mammalian vestibular organs
    Ruth Anne Eatock; Fiscal Year: 2012
    ..We will investigate whether specific CBPs help set firing patterns by modulating calcium-dependent potassium channels. We will develop computational models to test our comprehensive understanding of how ion channels contribute ..
  44. Assembly and Trafficking of IK1 and SK3 in Endothelia
    Daniel C Devor; Fiscal Year: 2012
    ..PUBLIC HEALTH RELEVANCE: Both intermediate (IK) and small (SK) conductance, calcium-activated potassium channels are expressed in microvascular endothelial cells where they play a crucial role in maintaining vascular tone ..
  45. Excitability mechanisms of neurocardiac regulation
    ALBERT E GLASSCOCK; Fiscal Year: 2013
    ..abstract_text> ..
  46. Potassium Channel Dysfunction in Cerebral Arteries
    David W Busija; Fiscal Year: 2013
    ..Current treatment regimens are not optimal and we expect that the results of our studies will lead to new and improved therapies to prevent or slow the onset of neurological diseases in an obese and aging population. ..
  47. ACUTE AIRWAY EFFECTS OF TLR7 AND TLR8 STIMULATION IN HEALTH AND DISEASE
    David B Jacoby; Fiscal Year: 2013
    ....
  48. Nanion Syncro Patch 96
    Gordana Vunjak-Novakovic; Fiscal Year: 2012
    ..for novel drugs to treat intracellular calcium leak in heart failure, (iv) Modulation of voltage-dependent potassium channels;(v) Determination of the structural inter-subunit interface in a key smooth muscle potassium channel, (vi) ..
  49. 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. ..
  50. Imaging cellular energy metabolism in brain slices using fluorescent biosensors
    REBECCA ANNE MONGEON; Fiscal Year: 2013
    ..the energy status of the cell, and ketone body metabolism may lower ATP levels and activate ATP-sensitive potassium channels that reduce neuronal excitability...
  51. 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. ..
  52. Characterization of Potassium Channels in the Human Parasite Trypanosoma Cruzi
    Veronica Jimenez; Fiscal Year: 2012
    ..Analysis of T. cruzi potassium channels expression profiles and localization, complemented with electrophysiological studies will shed light about ..
  53. Cellular physiology of epilepsy-associated KCNQ2 channels
    ANASTASIOS TZINGOUNIS; Fiscal Year: 2013
    ..Such work will provide an improved understanding of innate mechanisms that prevent epileptogenesis and could lead to the development of novel anti-epileptic drugs. ..
  54. Effect of sarcolemmal KATP channels on ROS/RNS generation and calcium handling
    Richard J Gumina; Fiscal Year: 2013
    ..This research will provide critical understanding ofthe mechanisms by which sarc-KATP channels influence the susceptibility to myocardial ischemia-reperfusion injury...
  55. Chemical biology of voltage-gated sodium and potassium channels
    Christopher A Ahern; Fiscal Year: 2013
    ..Success of the proposed study will make it possible to generate novel amino acids that will be widely available to the research community. ..
  56. DEVELOPMENT OF EXCITATION IN HAIR CELLS
    BERND H SOKOLOWSKI; Fiscal Year: 2013
    ..Moreover, these discoveries will provide insights into major intracellular pathways that regulate not only normal cochlear development but those that lead to sensorineural deafness in children. ..
  57. Anesthetic Action: Molecular Substrates &Neural Mechanisms
    Douglas A Bayliss; Fiscal Year: 2013
    ..anesthetic-sensitive ion channels - HCN hyperpolarization- activated cation channels and TASK background potassium channels - in mediating clinically important anesthetic actions...
  58. Role of serum- and glucocorticoid-regulated kinase-1 in electrical remodeling
    Anthony Rosenzweig; Fiscal Year: 2013
    ..kinases, such as Akt1, but also has unique downstream effects including modulation of ion channels such as potassium channels and the cardiac sodium channel, SCN5a...
  59. Chaperone Assisted Crystallography
    Anthony A Kossiakoff; Fiscal Year: 2012
    ....
  60. Biacore T100 SPR system for studying and characterizing biomolecular interaction
    Ewa Folta Stogniew; Fiscal Year: 2009
    ....
  61. GENETIC VULNERABILITY TO DRUGS OF ABUSE
    Kari J Buck; Fiscal Year: 2013
    ..This can direct further mechanistic studies and elucidate the important network(s), within which many biomarkers and drugable targets may exist to direct translational studies. ..
  62. VERGFR-1 in the Uterine Circulation During Pregnancy
    George J Osol; Fiscal Year: 2011
    ..Surprisingly little is known about its actions on the blood vessels of the uterus, and this project will determine the mechanisms by which it mediates uterine vascular changes during gestation. ..
  63. CYTOSOLIC REGULATION OF INNER EAR ION TRANSPORT
    A PHILINE WANGEMANN; Fiscal Year: 2007
    ..marginal cells in stria vascularis Under Specific Aim 2, we will detelmine the subunit composition of the potassium channels KCNQ1 in strial marginal cells, KCNQ4 in outer hair cells and KCNJ10 in strial intermediate cells These ..
  64. GENETICS OF NEMATODE PHARYNGEAL MUSCLE EXCITABILITY
    Leon Avery; Fiscal Year: 2003
    ..2) Calcium-activated potassium channels contribute to the decay of membrane potential during the plateau phase of the pharyngeal muscle action ..
  65. HUMAN SPERM ZONA ACCEPTOR: ENVIRONMENTAL EFFECTS
    Susan Benoff; Fiscal Year: 2005
    ..Outcome is test of hypothesis, and possible mechanism explaining infertility associated with low sperm counts or idiopathic male infertility, tools for diagnosis, and hope for treatment. ..
  66. PATCH CLAMP STUDY OF GASTROINTESTINAL NEURONS
    JACKIE WOOD; Fiscal Year: 1999
    ..at rest; 2) voltage activation of high threshold N-type calcium channels; 3) conduction in calcium-activated potassium channels; 4) voltage activation of A-type and delayed rectifier potassium channels...
  67. MUSCARINIC AND ADENOSINE RECEPTOR SIGNAL TRANSDUCTION
    Richard Mortensen; Fiscal Year: 2001
    ..G-proteins to directly and indirectly (via second messengers) regulate ion channels (inwardly rectifying potassium channels, acetylcholine activated potassium channels, L-type calcium channels, and pacemaker channels)...
  68. NICOTINE INDUCED CEREBROVASCULAR DYSFUNCTION
    WILLIAM MAYHAN; Fiscal Year: 2006
    ..In aim #2, we will determine the effects of nicotine on reactivity of cerebral arterioles to activation of potassium channels. Activation of potassium channels plays an important role in the regulation of cerebrovascular tone in ..
  69. Role of glycosylation in voltage-gated potassium channels
    Desiree A Thayer; Fiscal Year: 2010
    b>Potassium channels are key components for the electrical properties of excitable cells, and voltage-gated potassium channels (Kv) control neuronal excitability...
  70. Mechanisms of regulation of excitability in immature CNS
    Joaquin N Lugo; Fiscal Year: 2010
    ..In adult brain potassium channels are major determinants of membrane excitability in neurons. One particular potassium channel, Kv4...
  71. DEVELOPMENT OF THE XENOPUS ACOUSTICO-VESTIBULAR SYSTEM
    ELBA SERRANO; Fiscal Year: 2002
    ..The potassium channels of the inner ear will be a central subject of these investigations, and will be used to test hypotheses ..
  72. GENETIC STUDIES OF THE SYNAPSE
    Lily Jan; Fiscal Year: 2000
    b>Potassium channels are a large and diverse group of ion channels found in most eukaryotic cells. They control the electrical potential across the cell membrane and the excitability of nerve and muscle cells...
  73. Development of HTS Assays for Sub-Threshold Potassium Channels
    Timothy Jegla; Fiscal Year: 2006
    Voltage-gated potassium channels that are activated below the threshold for action potential initiation have a profound influence on neuronal excitability...
  74. MOLECULAR ORGANIZATION OF ION CHANNELS--A NOVEL APPROACH
    Anatoli Lopatin; Fiscal Year: 1999
    ..It uses the physical flow of thallium (Tl+) ions through individual potassium channels to produce specific, weakly soluble, inorganic microcrystals with some halide anions and transition metals ..
  75. A Novel High Throughput Assay for Ion Channel Modulators
    Barbara Wible; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable] [unreadable] [unreadable]..