potassium channel blockers

Summary

Summary: A class of drugs that act by inhibition of potassium efflux through cell membranes. Blockade of potassium channels prolongs the duration of ACTION POTENTIALS. They are used as ANTI-ARRHYTHMIA AGENTS and VASODILATOR AGENTS.

Top Publications

  1. pmc Neural KCNQ (Kv7) channels
    David A Brown
    Department of Pharmacology, University College London, London, UK
    Br J Pharmacol 156:1185-95. 2009
  2. ncbi Blockade of the intermediate-conductance calcium-activated potassium channel as a new therapeutic strategy for restenosis
    Ralf Köhler
    Department of Nephrology, Benjamin Franklin Medical Center, Berlin, Germany
    Circulation 108:1119-25. 2003
  3. 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
  4. 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
  5. pmc Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases
    Christine Beeton
    Department of Physiology and Biophysics, University of California, Irvine, CA 92697, USA
    Proc Natl Acad Sci U S A 103:17414-9. 2006
  6. 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
  7. ncbi Targeting effector memory T cells with a selective peptide inhibitor of Kv1.3 channels for therapy of autoimmune diseases
    Christine Beeton
    Department of Physiology and Biophysics, 291 Irvine Hall, Medical School, University of California Irvine, Irvine, CA 92697 4561, USA
    Mol Pharmacol 67:1369-81. 2005
  8. ncbi Structural basis of a potent peptide inhibitor designed for Kv1.3 channel, a therapeutic target of autoimmune disease
    Song Han
    State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China
    J Biol Chem 283:19058-65. 2008
  9. ncbi Monoclonal antibody blockade of the human Eag1 potassium channel function exerts antitumor activity
    David Gomez-Varela
    Max Planck Institute of Experimental Medicine, Gottingen, Germany
    Cancer Res 67:7343-9. 2007
  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

  1. Mechanisms of Synaptic Integration in Central Neurons
    William J Spain; Fiscal Year: 2012
  2. GENETIC STUDIES OF THE SYNAPSE
    Lily Jan; Fiscal Year: 2000
  3. ACUTE REPAIR OF SPINAL INJURY WITH FUSOGENS
    Richard Borgens; Fiscal Year: 2002
  4. EFFECTS OF K CHANNEL OPENERS ON CORONARY ARTERIES
    STEPHEN O ROURKE; Fiscal Year: 1992
  5. MORPHOPHYSIOLOGY OF VESTIBULAR ENDORGANS
    Richard Baird; Fiscal Year: 1991
  6. PERIPHERAL NEUROPATHY FOLLOWING THERMAL INJURY
    WILLIAM MONAFO; Fiscal Year: 1991
  7. TRIDENT
    A Chamberlin; Fiscal Year: 2001
  8. SYMPTOMATIC TREATMENT OF PERIPHERAL NEUROPATHIES
    Jinliang Sui; Fiscal Year: 2001
  9. EFFECTIVE SYNAPTIC CURRENTS IN MOTONEURONS
    Marc Binder; Fiscal Year: 2004
  10. Dietary Omega-3 Fatty Acids and Sudden Cardiac Death
    GEORGE EDWARD BILLMAN; Fiscal Year: 2010

Detail Information

Publications271 found, 100 shown here

  1. pmc Neural KCNQ (Kv7) channels
    David A Brown
    Department of Pharmacology, University College London, London, UK
    Br J Pharmacol 156:1185-95. 2009
    ..Flupirtine is in use as a central analgesic; retigabine is under clinical trial as a broad-spectrum anticonvulsant and is an effective analgesic in animal models of chronic inflammatory and neuropathic pain...
  2. ncbi Blockade of the intermediate-conductance calcium-activated potassium channel as a new therapeutic strategy for restenosis
    Ralf Köhler
    Department of Nephrology, Benjamin Franklin Medical Center, Berlin, Germany
    Circulation 108:1119-25. 2003
    ..In a rat model of balloon catheter injury (BCI), we investigated whether alterations in expression of Ca2+-activated K+ channels (KCa) contribute to intimal hyperplasia and vascular restenosis...
  3. 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...
  4. 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
    ..This bend would occur at a Pro-X-Pro sequence that is highly conserved in Kv channels, near the site of activation gating...
  5. pmc Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases
    Christine Beeton
    Department of Physiology and Biophysics, University of California, Irvine, CA 92697, USA
    Proc Natl Acad Sci U S A 103:17414-9. 2006
    ..Repeated dosing with Kv1.3 inhibitors in rats has not revealed systemic toxicity. Further development of Kv1.3 blockers for autoimmune disease therapy is warranted...
  6. 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
    ....
  7. ncbi Targeting effector memory T cells with a selective peptide inhibitor of Kv1.3 channels for therapy of autoimmune diseases
    Christine Beeton
    Department of Physiology and Biophysics, 291 Irvine Hall, Medical School, University of California Irvine, Irvine, CA 92697 4561, USA
    Mol Pharmacol 67:1369-81. 2005
    ..ShK(L5) prevents and treats experimental autoimmune encephalomyelitis and suppresses delayed type hypersensitivity in rats. ShK(L5) might prove useful for therapy of autoimmune disorders...
  8. ncbi Structural basis of a potent peptide inhibitor designed for Kv1.3 channel, a therapeutic target of autoimmune disease
    Song Han
    State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China
    J Biol Chem 283:19058-65. 2008
    ....
  9. ncbi Monoclonal antibody blockade of the human Eag1 potassium channel function exerts antitumor activity
    David Gomez-Varela
    Max Planck Institute of Experimental Medicine, Gottingen, Germany
    Cancer Res 67:7343-9. 2007
    ..The particular antibody described here, as well as the technique developed to make additional functional antibodies to Eag1, makes it possible to evaluate the potential of the channel as a target for cancer therapy...
  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. 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...
  12. pmc Analogs of the sea anemone potassium channel blocker ShK for the treatment of autoimmune diseases
    Christine Beeton
    Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030, USA
    Inflamm Allergy Drug Targets 10:313-21. 2011
    ..They are currently undergoing further evaluation as potential immunomodulators for the treatment of autoimmune diseases...
  13. 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...
  14. ncbi Role of voltage-gated potassium channels in cancer
    L A Pardo
    Max Planck Institute of Experimental Medicine, Hermann Rein Str 3, Gottingen, 37075 Germany
    J Membr Biol 205:115-24. 2005
    ..Molecular imaging of Eag1 in live tumor models has been accomplished with dye-tagged antibodies using 3-D imaging techniques in the near-infrared spectral range...
  15. ncbi Mapping the receptor site for hanatoxin, a gating modifier of voltage-dependent K+ channels
    K J Swartz
    Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Neuron 18:675-82. 1997
    ..These results suggest that residues near the outer edges of S3 and S4 form the HaTx binding sites and are eccentrically located at least 15 A from the central pore axis on the surface of voltage-gated K+ channels...
  16. pmc General Sensitization of melanoma cells for TRAIL-induced apoptosis by the potassium channel inhibitor TRAM-34 depends on release of SMAC
    Sandra Annika Quast
    Department of Dermatology and Allergy, Skin Cancer Center, University Medical Center Charite, Berlin, Germany
    PLoS ONE 7:e39290. 2012
    ..As both TRAIL and IK1 inhibitors had shown only minor side effects in clinical trials, a clinical application of this combination is conceivable...
  17. ncbi A bifunctional sea anemone peptide with Kunitz type protease and potassium channel inhibiting properties
    Steve Peigneur
    Laboratory of Toxicology, University of Leuven K U Leuven, Campus Gasthuisberg O and N2, Herestraat, Belgium
    Biochem Pharmacol 82:81-90. 2011
    ..In conclusion, this study demonstrates that APEKTx1 has the unique feature to combine the dual functionality of a potent and selective blocker of K(V)1.1 channels with that of a competitive inhibitor of trypsin...
  18. ncbi Potassium channel blockers attenuate hypoxia- and ischemia-induced neuronal death in vitro and in vivo
    Ling Wei
    Center for the Study of Nervous System Injury and Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
    Stroke 34:1281-6. 2003
    ....
  19. pmc Block of mouse Slo1 and Slo3 K+ channels by CTX, IbTX, TEA, 4-AP and quinidine
    Qiong Yao Tang
    Department of Anesthesiology, Washington University School of Medicine, St Louis, MO, USA
    Channels (Austin) 4:22-41. 2010
    ..The quinidine concentrations effective in blocking Slo3 suggest, that in experiments that have examined quinidine effects on sperm, any Slo3 currents would be almost completely inhibited...
  20. ncbi Selective blockade of the intermediate-conductance Ca2+-activated K+ channel suppresses proliferation of microvascular and macrovascular endothelial cells and angiogenesis in vivo
    Ivica Grgic
    Department of Nephrology, Charite, Campus Benjamin Franklin, Berlin, Germany
    Arterioscler Thromb Vasc Biol 25:704-9. 2005
    ..Here, we tested whether the intermediate-conductance K(Ca) channel (IKCa1) and the large-conductance K(Ca) channel (BK(Ca)) contribute to endothelial cell (EC) proliferation and angiogenesis...
  21. pmc Imaging of effector memory T cells during a delayed-type hypersensitivity reaction and suppression by Kv1.3 channel block
    Melanie P Matheu
    Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697 4561, USA
    Immunity 29:602-14. 2008
    ..3 channels in Tem cells during an inflammatory immune response in peripheral tissues. Targeting Kv1.3 allows for effector memory responses to be suppressed while central memory responses remain intact...
  22. 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...
  23. ncbi Activity of potassium channel-blockers in breast cancer
    Mansoor Abdul
    Edward Via Virginia College of Osteopathic Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
    Anticancer Res 23:3347-51. 2003
    ..Potassium ion (K+) channels are known to play a key role in breast cancer proliferation...
  24. ncbi Inhibition of the Ca²⁺-dependent K⁺ channel, KCNN4/KCa3.1, improves tissue protection and locomotor recovery after spinal cord injury
    Delphine Bouhy
    Centre for Research in Neuroscience, The Research Institute of the McGill University Health Center, Montreal, Quebec H3G1A4, Canada
    J Neurosci 31:16298-308. 2011
    ..These results suggest that blocking the KCa3.1 channel could be a potential therapeutic approach for treating secondary damage after spinal cord injury...
  25. pmc K+ channel modulators for the treatment of neurological disorders and autoimmune diseases
    Heike Wulff
    Department of Pharmacology, University of California, Davis, California 95616, USA
    Chem Rev 108:1744-73. 2008
  26. ncbi Kv1.2-containing K+ channels regulate subthreshold excitability of striatal medium spiny neurons
    Weixing Shen
    Department of Physiology and Institute for Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
    J Neurophysiol 91:1337-49. 2004
    ..These studies establish a clear functional role for somato-dendritic Kv1.2 channels in the regulation of state transitions and repetitive discharge in striatal medium spiny neurons...
  27. pmc Local delivery of the KCa3.1 blocker, TRAM-34, prevents acute angioplasty-induced coronary smooth muscle phenotypic modulation and limits stenosis
    D L Tharp
    Department of Biomedical Sciences, University of Missouri, Columbia, MO 65211, USA
    Arterioscler Thromb Vasc Biol 28:1084-9. 2008
    ..The objective of the present study was to determine the role of K(Ca)3.1 in the regulation of coronary SMC phenotypic modulation in vivo using a swine model of postangioplasty restenosis...
  28. pmc Engineering a stable and selective peptide blocker of the Kv1.3 channel in T lymphocytes
    M W Pennington
    Bachem Bioscience Inc, King of Prussia, Pennsylvania, USA
    Mol Pharmacol 75:762-73. 2009
    ..ShK-192 has potential as a therapeutic for autoimmune diseases mediated by T(EM) cells...
  29. pmc Involvement of Kv1.3 and p38 MAPK signaling in HIV-1 glycoprotein 120-induced microglia neurotoxicity
    J Liu
    Neurophysiology Laboratory, Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198 5880, USA
    Cell Death Dis 3:e254. 2012
    ..3 expression and resultant neurotoxic activity. These results suggest not only a role K(v)1.3 may have in gp120-associated microglia neurotoxic activity, but also a potential target for the development of therapeutic strategies...
  30. pmc The antibody targeting the E314 peptide of human Kv1.3 pore region serves as a novel, potent and specific channel blocker
    Xiao fang Yang
    Department of Cardiology, Union Hospital, Huazhong University of Science and Technology, Wuhan, China
    PLoS ONE 7:e36379. 2012
    ..1 channels and functional cardiac ion channels underlying central nervous system (CNS) disorders or drug-acquired arrhythmias, which is required as a safe clinic-promising channel blocker...
  31. ncbi K(+) channels as therapeutic drug targets
    Alan Wickenden
    Icagen Inc, Suite 460, 4222 Emperor Boulevard, Durham, NC 27703, USA
    Pharmacol Ther 94:157-82. 2002
    ..The identification of these molecular K(+) channel drug targets should lead to the discovery of novel drug candidates. A summary of progress is presented...
  32. ncbi A new class of scorpion toxin binding sites related to an A-type K+ channel: pharmacological characterization and localization in rat brain
    H Vacher
    , , Marseille, France
    FEBS Lett 501:31-6. 2001
    ..A high density of 125I-sBmTX3 binding sites was found in the striatum, hippocampus, superior colliculus, and cerebellum in the adult rat brain...
  33. ncbi Calcium-activated transient outward chloride current and phase 1 repolarization of swine ventricular action potential
    Gui Rong Li
    Institute of Cardiovascular Science and Medicine Department of Medicine, The University of Hong Kong, Hong Kong SAR, China
    Cardiovasc Res 58:89-98. 2003
    ..Cl) or I(to2)) contribute(s) to phase 1 repolarization of pig ventricular action potential (AP). The purpose of the present study was to determine ionic contribution of the phase 1 repolarization of AP in pig ventricle...
  34. ncbi Role of IKur in controlling action potential shape and contractility in the human atrium: influence of chronic atrial fibrillation
    Erich Wettwer
    Department of Pharmacology and Toxicology, Dresden University of Technology, Dresden, Germany
    Circulation 110:2299-306. 2004
    ....
  35. ncbi RSD1235 blocks late INa and suppresses early afterdepolarizations and torsades de pointes induced by class III agents
    Peter M R Orth
    Cardiome Pharma Corporation, 6th Floor, Vancouver BC, Canada
    Cardiovasc Res 70:486-96. 2006
    ..Further, RSD1235's ability to reverse the pro-arrhythmic actions of the class III agents dofetilide and clofilium was assessed in isolated Purkinje fibers and an in vivo model of torsades de pointes (TdP)...
  36. ncbi Gating modifier peptides as probes of pancreatic beta-cell physiology
    James Herrington
    Merck Research Laboratories, Department of Ion Channels, Rahway, RY80N C31, PO Box 2000, Rahway, NJ 07065 0900, USA
    Toxicon 49:231-8. 2007
    ..1 channels may be a useful approach to the design of novel therapeutic agents for the treatment of type 2 diabetes. These studies highlight the utility of gating modifier peptides in the study of physiological systems...
  37. ncbi Potassium channel blockers as an effective treatment to restore impulse conduction in injured axons
    Riyi Shi
    Department of Basic Medical Sciences, School of Veterinary Medicine, Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana 47907, USA
    Neurosci Bull 27:36-44. 2011
    ..Further translational research has also identified several novel potassium channel blockers that may prove effective in restoring axonal conduction.
  38. ncbi Animal toxins acting on voltage-gated potassium channels
    Stephanie Mouhat
    Ingénierie des peptides à visée thérapeutique, ERT 62, Université de Méditerranée Ambrilia Biopharma Inc, Faculte de Medecine Nord, Bvd P Dramard, 13916 Marseille Cedex 20, France
    Curr Pharm Des 14:2503-18. 2008
    ..The diversity of Kv channel blockers and their therapeutic value in the potential treatment of a number of specific human diseases, especially autoimmune disorders, inflammatory neuropathies and cancer, are reviewed...
  39. pmc Deletion of the Slo3 gene abolishes alkalization-activated K+ current in mouse spermatozoa
    Xu Hui Zeng
    Department of Anesthesiology, Washington University School of Medicine, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 108:5879-84. 2011
    ....
  40. ncbi Guanosine is neuroprotective against oxygen/glucose deprivation in hippocampal slices via large conductance Ca²+-activated K+ channels, phosphatidilinositol-3 kinase/protein kinase B pathway activation and glutamate uptake
    T Dal-Cim
    Departamento de Bioquimica, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Trindade, 88040 900 Florianopolis, SC, Brazil
    Neuroscience 183:212-20. 2011
    ..Moreover, neuroprotection caused by guanosine depends on the increased expression of phospho-Akt protein...
  41. ncbi Modulation of ERG channels by XE991
    Pernille Elmedyb
    Department of Medical Physiology, The Panum Institute, The University of Copenhagen, Denmark
    Basic Clin Pharmacol Toxicol 100:316-22. 2007
    ..XE991 and linopiridine are known to be standard KCNQ potassium channel blockers. These compounds have been used in many different tissues as specific pharmacological tools to discern ..
  42. ncbi Functional importance of Ca2+-activated K+ channels for lysophosphatidic acid-induced microglial migration
    Tom Schilling
    Institute of Physiology, Humboldt University Berlin, Tucholsky Strasse 2, D 10117 Berlin, Germany
    Eur J Neurosci 19:1469-74. 2004
    ..Microglial migration was not inhibited by 5 micro m paxilline. It is concluded that IKCa1 Ca(2+)-activated K(+) channels are required for LPA-stimulated migration of microglial cells...
  43. ncbi Blockage of intermediate-conductance Ca2+-activated K+ channels inhibit human pancreatic cancer cell growth in vitro
    Heike Jäger
    Department of Applied Physiology, University Ulm, Ulm, Germany
    Mol Pharmacol 65:630-8. 2004
    ..The blockade of IK channels may ultimately prove useful as a therapeutic option for some patients with ductal adenocarcinoma of the pancreas with an up-regulated IK channel expression...
  44. ncbi A phase 3 trial of extended release oral dalfampridine in multiple sclerosis
    Andrew D Goodman
    Department of Neurology, University of Rochester Medical Center, Rochester, NY 14642, USA
    Ann Neurol 68:494-502. 2010
    ..The current study was designed to confirm efficacy and further define safety and pharmacodynamics...
  45. pmc The pore structure and gating mechanism of K2P channels
    Paula L Piechotta
    Universitatsklinikum Jena, Institute of Physiology II, Jena, Germany
    EMBO J 30:3607-19. 2011
    ..These results demonstrate that the primary activation mechanisms in TREK-1 reside close to, or within the selectivity filter and do not involve gating at the cytoplasmic bundle crossing...
  46. pmc Specific antibodies to the external vestibule of voltage-gated potassium channels block current
    B Y Zhou
    Department of Physiology, Cornell University Medical College, New York 10021, USA
    J Gen Physiol 111:555-63. 1998
    ..2 to the overall endogenous K+ currents in NG108 neuronal cells. This guided design of specific channel blockers will facilitate future physiological studies on ion channel functions...
  47. ncbi Molecular diversity of the telson and venom components from Pandinus cavimanus (Scorpionidae Latreille 1802): transcriptome, venomics and function
    Elia Diego-Garcia
    Laboratory of Toxicology, University of Leuven, Campus Gasthuisberg, Leuven, Belgium
    Proteomics 12:313-28. 2012
    ..Expressed sequence tags from venom glands provide complementary information to MS and reveal undescribed components related to the biological activity of the venom...
  48. pmc Potassium channels Kv1.1, Kv1.2 and Kv1.6 influence excitability of rat visceral sensory neurons
    Patricia A Glazebrook
    Department of Neurosciences, Case Western Reserve University, Cleveland, OH 44109, USA
    J Physiol 541:467-82. 2002
    ....
  49. ncbi Interaction simulation of hERG K+ channel with its specific BeKm-1 peptide: insights into the selectivity of molecular recognition
    Hong Yi
    State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, People s Republic of China
    J Proteome Res 6:611-20. 2007
    ....
  50. ncbi Transient limb ischemia induces remote preconditioning and remote postconditioning in humans by a K(ATP)-channel dependent mechanism
    Stavros P Loukogeorgakis
    Vascular Physiology Unit, Institute of Child Health, University College London, 34 Great Ormond St, London, WC1N 3JE, UK
    Circulation 116:1386-95. 2007
    ..Using an in vivo model of endothelial IR injury, we sought to determine whether RPostC occurred in humans and whether it shared mechanistic similarities with RIPC...
  51. ncbi KCNQ/M channels control spike afterdepolarization and burst generation in hippocampal neurons
    Cuiyong Yue
    Department of Physiology, Institute of Medical Sciences, Hebrew University Hadassah Faculty of Medicine, Jerusalem 91120, Israel
    J Neurosci 24:4614-24. 2004
    ..Consequently, down-modulation of KCNQ/M channels converts the neuronal firing pattern from simple to complex spiking, whereas up-modulation of these channels exerts the opposite effect...
  52. pmc Revealing the structural basis of action of hERG potassium channel activators and blockers
    Matthew Perry
    University of Utah, Department of Physiology, Nora Eccles Harrison Cardiovascular Research and Training Institute, 95 South 2000 East, Salt Lake City, UT 84112, USA
    J Physiol 588:3157-67. 2010
    ..They reveal not only novel ways of chemically manipulating hERG channel function, but also interactions between structural domains that are critical to normal activation and inactivation gating...
  53. ncbi Minocycline decreases in vitro microglial motility, beta1-integrin, and Kv1.3 channel expression
    Nancy Nutile-McMenemy
    Department of Anesthesiology, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire, USA
    J Neurochem 103:2035-46. 2007
    ....
  54. 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...
  55. 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...
  56. pmc Modulation of vascular function by perivascular adipose tissue: the role of endothelium and hydrogen peroxide
    Y J Gao
    Department of Anesthesia, Smooth Muscle Research Program, McMaster University, Hamilton, Ontario, Canada
    Br J Pharmacol 151:323-31. 2007
    ..Perivascular adipose tissue (PVAT) attenuates vascular contraction, but the mechanisms remain largely unknown. The possible involvement of endothelium (E) and hydrogen peroxide (H2O2) was investigated...
  57. ncbi Periadventitial fat releases a vascular relaxing factor
    Matthias Löhn
    HELIOS Klinikum Berlin, Franz Volhard Clinic and Max Delbrück Center for Molecular Medicine, Medical Faculty of the Charite, Humboldt University of Berlin, Germany
    FASEB J 16:1057-63. 2002
    ..We suggest that perivascular adventitial adipose tissue releases a transferable adventitium-derived relaxing factor that acts by tyrosine kinase-dependent activation of K+ channels in vascular smooth muscle cells...
  58. 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...
  59. ncbi Two heteromeric Kv1 potassium channels differentially regulate action potential firing
    Paul D Dodson
    Department of Cell Physiology and Pharmacology, University of Leicester, Leicester, LE1 9HN, United Kingdom
    J Neurosci 22:6953-61. 2002
    ..Our results show that heteromeric channels containing Kv1.2 subunits govern AP firing and suggest that their localization at the initial segment of MNTB axons can explain their dominance of AP firing behavior...
  60. ncbi Combined receptor and ligand-based approach to the universal pharmacophore model development for studies of drug blockade to the hERG1 pore domain
    Serdar Durdagi
    Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada
    J Chem Inf Model 51:463-74. 2011
    ..The average docking score differences between wild type and mutated hERG channels was found to have the following order: F656A > Y652A > S624A > T623A > S649A. These results are in agreement with experimental data...
  61. ncbi Adiponectin is a novel humoral vasodilator
    Gábor Fésüs
    Charite University Medicine Berlin, Germany
    Cardiovasc Res 75:719-27. 2007
    ..We tested the hypothesis that ADRF might be adiponectin and that adiponectin plays a role in the paracrine control of vascular tone by perivascular adipose tissue...
  62. pmc High-throughput screening reveals a small-molecule inhibitor of the renal outer medullary potassium channel and Kir7.1
    L Michelle Lewis
    Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Mol Pharmacol 76:1094-103. 2009
    ..Electrophysiological analysis indicates that VU590 is an intracellular pore blocker. VU590 and other compounds identified by HTS will be instrumental in defining Kir channel structure, physiology, and therapeutic potential...
  63. ncbi Different residues in channel turret determining the selectivity of ADWX-1 inhibitor peptide between Kv1.1 and Kv1.3 channels
    Shi Jin Yin
    State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, PR China
    J Proteome Res 7:4890-7. 2008
    ..3 over Kv1.1. Mutation of Kv1.1 turret residues to match the sequence of Kv1.3 lead to increased inhibition of Kv1.1 activity. These studies may lead to improvements in peptide inhibitor drug development...
  64. pmc Regulation of cell proliferation by intermediate-conductance Ca2+-activated potassium and volume-sensitive chloride channels in mouse mesenchymal stem cells
    Rong Tao
    Dept of Medicine, L8 01, Laboratory Block, FMB, The Univ of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR China
    Am J Physiol Cell Physiol 295:C1409-16. 2008
    ..Collectively, our results have demonstrated that IK(Ca) and I(Cl.vol) channels regulate cell cycle progression and proliferation of mouse MSCs by modulating cyclin D1 and cyclin E expression...
  65. pmc Electrophysiological and functional effects of the KCNQ channel blocker XE991 on murine portal vein smooth muscle cells
    Shuk Yin M Yeung
    Department of Basic Medical Sciences, St George s University of London, Cranmer Terrace, London SW17 0RE
    Br J Pharmacol 146:585-95. 2005
    ..The stimulatory effect of XE991 was not affected by the presence of 4-AP, glibenclamide nor paxilline. These data provide evidence for an important role for KCNQ channels in governing cellular excitability in mPV smooth muscle cells...
  66. ncbi Potassium channel blockers in multiple sclerosis: neuronal Kv channels and effects of symptomatic treatment
    Susan I V Judge
    MS Center of Excellence East, Research and Neurology Services, VA Maryland Health Care System, USA
    Pharmacol Ther 111:224-59. 2006
    ....
  67. ncbi Kv1.3 voltage-gated K(+) channel subunit as a potential diagnostic marker and therapeutic target for breast cancer
    Soo Hwa Jang
    Laboratories of Veterinary Pharmacology, College of Veterinary Medicine, Seoul National University, Seoul 151 742, Korea
    BMB Rep 42:535-9. 2009
    ..Therefore, Kv1.3 may serve as a novel molecular target for breast cancer therapy while its stage-specific expression pattern may provide a potential diagnostic marker for breast cancer development...
  68. pmc State-dependent block of BK channels by synthesized shaker ball peptides
    Weiyan Li
    Section of Neurobiology, University of Texas at Austin, Austin, TX 78712, USA
    J Gen Physiol 128:423-41. 2006
    ..Furthermore, our results from two BK channel mutations demonstrate that similar types of interactions between ball peptides and channels are shared by BK and other K(+) channel types...
  69. ncbi KCNKØ: opening and closing the 2-P-domain potassium leak channel entails "C-type" gating of the outer pore
    N Zilberberg
    Department of Pediatrics, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06536, USA
    Neuron 32:635-48. 2001
    ..We conclude that similar outer pore gates mediate KCNKØ opening and closing and VGK channel C-type inactivation despite their divergent structures and physiological roles...
  70. pmc Expression and isotopic labelling of the potassium channel blocker ShK toxin as a thioredoxin fusion protein in bacteria
    Shih Chieh Chang
    Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia
    Toxicon 60:840-50. 2012
    ..This expression system also enables the efficient production of ¹⁵N-labelled ShK for NMR studies of peptide dynamics and of the interaction of ShK with Kv1.3 channels...
  71. ncbi Screening blockers against a potassium channel with a droplet interface bilayer array
    Ruhma Syeda
    Department of Chemistry, University of Oxford, Mansfield Road, Oxford, OX1 3TA, UK
    J Am Chem Soc 130:15543-8. 2008
    ..On the basis of these findings, we have devised a chip-based approach for the rapid screening of blockers against ion channels. The technique is demonstrated here with the viral potassium channel, Kcv...
  72. ncbi Purinergic activation of a leak potassium current in freshly dissociated myocytes from mouse thoracic aorta
    S Hayoz
    Department of Zoology and Animal Biology, University of Geneva, Sciences III, Geneva, Switzerland
    Acta Physiol (Oxf) 195:247-58. 2009
    ..Exogenous ATP elicits a delayed calcium-independent K(+) current on freshly isolated mouse thoracic aorta myocytes. We investigated the receptor, the intracellular pathway and the nature of this current...
  73. ncbi New polypeptide components purified from mamba venom
    J Tytgat
    Laboratory of Toxicology, University of Leuven, Belgium
    FEBS Lett 491:217-21. 2001
    ..1 channels with an IC(50) value in the range of 300 nM. They can be considered as new dendrotoxins, albeit with fairly low affinity as compared to alpha-DTX. 'DaE' polypeptides do not affect Kir2.1 channels...
  74. pmc Activated T-cells inhibit neurogenesis by releasing granzyme B: rescue by Kv1.3 blockers
    Tongguang Wang
    Department of Neurology, The Johns Hopkins University, Baltimore, Maryland 21287, USA
    J Neurosci 30:5020-7. 2010
    ..We have thus identified a novel pathway in neurogenesis. The increased expression of Kv1.3 in pathological conditions makes it a novel target for promoting neurorestoration...
  75. pmc Emerging roles for two-pore-domain potassium channels and their potential therapeutic impact
    Douglas A Bayliss
    Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA
    Trends Pharmacol Sci 29:566-75. 2008
    ..Development of compounds that selectively modulate K(2P) channels is crucial for verifying these results and assessing the efficacy of therapies targeting these interesting channels...
  76. ncbi Design of PAP-1, a selective small molecule Kv1.3 blocker, for the suppression of effector memory T cells in autoimmune diseases
    Alexander Schmitz
    Department of Medical Pharmacology and Toxicology, Genome and Biomedical Sciences Facility, Room 3502, 451 East Health Sciences Drive, University of California, Davis, Davis, CA 95616, USA
    Mol Pharmacol 68:1254-70. 2005
    ..PAP-1 and several of its derivatives therefore constitute excellent new tools to further explore Kv1.3 as a target for immunosuppression and could potentially be developed into orally available immunomodulators...
  77. ncbi Predicting drug-hERG channel interactions that cause acquired long QT syndrome
    Michael C Sanguinetti
    Department of Physiology and Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT 84112, USA
    Trends Pharmacol Sci 26:119-24. 2005
    ..Combined with pharmacophore models, knowledge of the drug-binding site of hERG channels will facilitate in silico design efforts to discover drugs that are devoid of this rare, but potentially lethal, side-effect...
  78. ncbi Anti-proliferative effect of Kv1.3 blockers in A549 human lung adenocarcinoma in vitro and in vivo
    Soo Hwa Jang
    College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Gwanak Gu, Seoul 151 742, South Korea
    Eur J Pharmacol 651:26-32. 2011
    ..These results suggest that Kv1.3 may serve as a novel therapeutic target for lung adenocarcinoma therapy...
  79. ncbi Molecular mechanism of δ-dendrotoxin-potassium channel recognition explored by docking and molecular dynamic simulations
    Ling Jin
    Department of Chemistry, School of Natural Science, Wuhan University of Technology, Wuhan, Hubei 430070, P R China
    J Mol Recognit 24:101-7. 2011
    ..Together, these novel data may accelerate the structure-function research of toxins in the dendrotoxin family and be of significant value in revealing the diverse interactions between animal toxins and potassium channels...
  80. ncbi The pH hypothesis of postconditioning: staccato reperfusion reintroduces oxygen and perpetuates myocardial acidosis
    Michael V Cohen
    Department of Physiology, MSB 3050, University of South Alabama, College of Medicine, Mobile, AL 36688, USA
    Circulation 115:1895-903. 2007
    ..Acidosis also suppresses MPTP formation. We tested whether postconditioning protects by maintaining acidosis during early reoxygenation...
  81. pmc The 'functional' dyad of scorpion toxin Pi1 is not itself a prerequisite for toxin binding to the voltage-gated Kv1.2 potassium channels
    Stephanie Mouhat
    Laboratoire International Associé d Ingénierie Biomoléculaire, Boulevard Pierre Dramard, 13916 Marseille Cedex 20, France
    Biochem J 377:25-36. 2004
    ..2 channels support an unexpected key role of specific basic amino acid residues, which form a basic ring (Arg-5, Arg-12, Arg-28 and Lys-31 residues), in toxin binding...
  82. ncbi Mapping of maurotoxin binding sites on hKv1.2, hKv1.3, and hIKCa1 channels
    Violeta Visan
    Department of Applied Physiology, University of Ulm, Albert Einstein Allee 11, D 89081 Ulm, Germany
    Mol Pharmacol 66:1103-12. 2004
    ..A negatively charged amino acid in this position could better stabilize the toxin-channel interaction and could explain the pH(o) sensitivity of MTX block on current through hIKCa1 versus hKv1.2 channels...
  83. ncbi Vasoconstrictive effect of hydrogen sulfide involves downregulation of cAMP in vascular smooth muscle cells
    Jia Jia Lim
    Dept of Pharmacology, Yong Loo Lin School of Medicine, National Univ of Singapore, Singapore, 117597
    Am J Physiol Cell Physiol 295:C1261-70. 2008
    ..Taken together, we demonstrated for the first time that the vasoconstrictive effect of H(2)S involves the adenyly cyclase/cAMP pathway...
  84. ncbi Mechanisms of tetraethylammonium ion block in the KcsA potassium channel
    V B Luzhkov
    Department of Cell and Molecular Biology, Uppsala University, BMC, Box 596, S-751 24, Uppsala, Sweden
    FEBS Lett 495:191-6. 2001
    ....
  85. pmc 4-Aminopyridine improves spatial memory in a murine model of HIV-1 encephalitis
    James P Keblesh
    Neurophysiology Laboratory, University of Nebraska Medical Center, Omaha, NE 68198 5880, USA
    J Neuroimmune Pharmacol 4:317-27. 2009
    ..These results support the importance of K(v) channel dysfunction in disease but, more importantly, provide a potential target for adjunctive therapies for HAND...
  86. pmc Molecular proximity of Kv1.3 voltage-gated potassium channels and beta(1)-integrins on the plasma membrane of melanoma cells: effects of cell adherence and channel blockers
    Vira V Artym
    Department of Biological Sciences, Wayne State University, Detroit, MI 48202, USA
    J Gen Physiol 120:29-37. 2002
    ..3 channels with beta1-integrins contributes to the regulation of integrin function and that channel blockers might affect tumor cell behavior by influencing the assembly of supramolecular structures containing integrins...
  87. ncbi An ERG channel inhibitor from the scorpion Buthus eupeus
    Y V Korolkova
    Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ul Miklukho Maklaya, 16 10, 117997, GSP 7, Moscow, Russia
    J Biol Chem 276:9868-76. 2001
    ..The mature toxin consists of 36 amino acid residues. BeKm-1 belongs to the family of scorpion venom potassium channel blockers and represents a new subgroup of these toxins...
  88. ncbi Acacetin causes a frequency- and use-dependent blockade of hKv1.5 channels by binding to the S6 domain
    Hui Jun Wu
    Department and Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
    J Mol Cell Cardiol 51:966-73. 2011
    ..These results demonstrate the novel information that acacetin mainly blocks open hKv1.5 channels by binding to their S6 domain. The use- and rate-dependent blocking of hKv1.5 by acacetin is beneficial for anti-atrial fibrillation...
  89. ncbi Differential effects of statins on endogenous H2S formation in perivascular adipose tissue
    Grazyna Wojcicka
    Department of Pathophysiology, Medical University, Jaczewskiego 8, 20 090 Lublin, Poland
    Pharmacol Res 63:68-76. 2011
    ..This effect is mediated by statin-induced CoQ(9) deficiency and results in the augmentation of anticontractile effect of perivascular adipose tissue...
  90. ncbi CXCL12-induced glioblastoma cell migration requires intermediate conductance Ca2+-activated K+ channel activity
    Miriam Sciaccaluga
    Istituto Pasteur Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy
    Am J Physiol Cell Physiol 299:C175-84. 2010
    ..All together these findings suggest that the efficacy of glioblastoma invasiveness might be related to an array of nonoverlapping mechanisms activated by different chemotactic agents...
  91. pmc A designer ligand specific for Kv1.3 channels from a scorpion neurotoxin-based library
    Zoltan Takacs
    Department of Pediatrics and Institute of Molecular Pediatric Sciences, Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, USA
    Proc Natl Acad Sci U S A 106:22211-6. 2009
    ..This scaffold-based/target-biased strategy overcomes many obstacles to production of selective toxins...
  92. ncbi K+ channel blockers: novel tools to inhibit T cell activation leading to specific immunosuppression
    G Panyi
    Department of Biophysics and Cell Biology, University of Debrecen, Medical and Health Science Center, 98 Nagyerdei krt, Debrecen 4012 Hungary
    Curr Pharm Des 12:2199-220. 2006
    ....
  93. pmc Two functionally distinct subsites for the binding of internal blockers to the pore of voltage-activated K+ channels
    T Baukrowitz
    Department of Neurobiology, Massachusetts General Hospital, Boston 02114, USA
    Proc Natl Acad Sci U S A 93:13357-61. 1996
    ..These interactions are important because they affect the ability of blockers to produce use-dependent inhibition...
  94. ncbi [Hydrogen sulfide induce negative inotropic effect in isolated hearts via KATP channel and mitochondria membrane KATP channel]
    Yan Sun
    Department of Pediatrics, Peking University First Hospital, Beijing 100034, China
    Zhonghua Xin Xue Guan Bing Za Zhi 37:161-4. 2009
    ..The study was designed to observe the role of mitochondria membrane K(ATP) channel blocker (5-HD) in the regulation of cardiac function isolated perfused heart of rat with H(2)S...
  95. ncbi Pharmacological removal of human ether-à-go-go-related gene potassium channel inactivation by 3-nitro-N-(4-phenoxyphenyl) benzamide (ICA-105574)
    Aaron C Gerlach
    Icagen, Inc, Durham, NC 27703, USA
    Mol Pharmacol 77:58-68. 2010
    ..This compound may provide a useful tool to further understand the mechanism by which hERG channels inactivate and affect cardiac function in addition to the role of hERG channels in other cell systems...
  96. ncbi Potassium channels in T lymphocytes: therapeutic targets for autoimmune disorders?
    Rosane Vianna-Jorge
    Divisão de Farmacologia, Coordenação de Pesquisa, Instituto Nacional de Cancer, Rio de Janeiro, Brazil
    BioDrugs 18:329-41. 2004
    ..3 or IKCa1, which could help the development of new drugs for safer treatment of auto-immune diseases...
  97. pmc Kir4.1 K+ channels are regulated by external cations
    Johan M Edvinsson
    Graduate Program in Physiology, Biophysics and Systems Biology, Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY, USA
    Channels (Austin) 5:269-79. 2011
    ....
  98. ncbi Mobilization of calcium from intracellular stores, potentiation of neurotransmitter-induced calcium transients, and capacitative calcium entry by 4-aminopyridine
    M Grimaldi
    Laboratory of Adaptive Systems, National Institute for Neurological Disorders and Stroke and National Institute of Deafness and other Communicative Disorders, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Neurosci 21:3135-43. 2001
    ..The potentiation of capacitative calcium entry in astrocytes or muscle cells may explain some of the therapeutic activities of 4-AP as a neurotransmission enhancer...
  99. ncbi A potent potassium channel blocker from Mesobuthus eupeus scorpion venom
    Bin Gao
    Group of Animal Innate Immunity, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, Beijing 100101, China
    Biochimie 92:1847-53. 2010
    ..3, an attractive target for T-cell mediated autoimmune diseases...
  100. ncbi Mice carrying the szt1 mutation exhibit increased seizure susceptibility and altered sensitivity to compounds acting at the m-channel
    James F Otto
    Anticonvulsant Drug Development Program, Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah 84112, USA
    Epilepsia 45:1009-16. 2004
    ....
  101. ncbi Selective blockage of Kv1.3 and Kv3.1 channels increases neural progenitor cell proliferation
    Stefan Liebau
    Department of Anatomy and Cell Biology, University of Ulm, Ulm, Germany
    J Neurochem 99:426-37. 2006
    ..3 by Psora-4, increased NPC proliferation. These findings underline the regulatory role of K(+) channels on the cell cycle and imply that K(+) channel modulators might be used therapeutically to activate endogenous NPCs...

Research Grants64

  1. Mechanisms of Synaptic Integration in Central Neurons
    William J Spain; Fiscal Year: 2012
    ..b>Potassium channel blockers and openers and receptor agonists and antagonists are applied to the neurons during the electrical ..
  2. GENETIC STUDIES OF THE SYNAPSE
    Lily Jan; Fiscal Year: 2000
    ..Given that potassium channel blockers or openers have been used to treat diseases such as arrythmia, hypertension and diabetes, it conceivable ..
  3. ACUTE REPAIR OF SPINAL INJURY WITH FUSOGENS
    Richard Borgens; Fiscal Year: 2002
    ..destruction (by complexed free radical scavengers) and facilitate nerve impulse conduction (by complexed potassium channel blockers)...
  4. EFFECTS OF K CHANNEL OPENERS ON CORONARY ARTERIES
    STEPHEN O ROURKE; Fiscal Year: 1992
    ..of all observed responses will be examined by performing studies in the presence of several known potassium channel blockers. The experiments described herein will provide exciting, new information regarding novel mechanisms for ..
  5. MORPHOPHYSIOLOGY OF VESTIBULAR ENDORGANS
    Richard Baird; Fiscal Year: 1991
    ..of the afferent nerve terminal will be measured in vitro before and after the administration of specific potassium channel blockers. To study the properties of synaptic input from type I and type II hair cells, attempts will be made in ..
  6. PERIPHERAL NEUROPATHY FOLLOWING THERMAL INJURY
    WILLIAM MONAFO; Fiscal Year: 1991
    ..axons in vivo and in vitro; this conduction block is reversible in vitro by 4-aminopyridine and other potassium channel blockers. The characteristics and mechanisms of this phenomenon will be explored: 1) by determining whether in ..
  7. TRIDENT
    A Chamberlin; Fiscal Year: 2001
    ..would explicitly benefit from the purchase of this instrument include: (a) Chamberlin, memory enhancers, potassium channel blockers, and selective inhibitors of protein phosphatases; (b) Feher, novel dendritic compounds with peptidic ..
  8. SYMPTOMATIC TREATMENT OF PERIPHERAL NEUROPATHIES
    Jinliang Sui; Fiscal Year: 2001
    ..we successfully established the basic screening technologies, developed a focused chemical library of potassium channel blockers and identified lead molecules...
  9. EFFECTIVE SYNAPTIC CURRENTS IN MOTONEURONS
    Marc Binder; Fiscal Year: 2004
    ..Aim 2 will examine the summation of synaptic currents in cat spinal motoneurons treated with internal potassium channel blockers, which have also been shown to induce voltage-dependent amplification of synaptic currents in ..
  10. Dietary Omega-3 Fatty Acids and Sudden Cardiac Death
    GEORGE EDWARD BILLMAN; Fiscal Year: 2010
    ..This project will also determine the effectiveness of fish oil supplements in reducing sudden death due to a lethal abnormal heart rhythm after a heart attack. ..
  11. Effect of Daily Exercise on Cardiac Autonomic Regulation
    GEORGE BILLMAN; Fiscal Year: 2005
    ..Ventricular contractile responses to Beta1- and Beta2-adrenoceptor stimulation will be examined in vivo by echocardiography and in vitro by single cell fluorescence microscopy/video edge detection. ..
  12. Transmitter Repletion: Key to Phrenic-Diaphragm Function
    Erik van Lunteren; Fiscal Year: 2005
    ..These studies may lead to novel therapeutic approaches to respiratory muscle impairment and resulting hypercapnic respiratory failure for conditions which produce neuromuscular junction dysfunction. ..
  13. 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. ..
  14. SK Channel Openers as Therapeutics for Cerebellar Ataxia
    Heike Wulff; Fiscal Year: 2007
    ..Taken together these important proof-of-concept studies will help to determine whether SK channel openers constitute a new therapeutic approach to improve motor performance in dominant cerebellar ataxias. ..
  15. Redox Regulation of Cardiac Electrical Remodeling
    GEORGE ROZANSKI; Fiscal Year: 2009
    ..PHS 398 (Rev. 09/04) Page 2 Principal Investigator/Program Director (Last, first, middle): Rozanski, George, J ..
  16. Development and study of specific Kir channel inhibitors
    Zhe Lu; Fiscal Year: 2009
    ..abstract_text> ..
  17. Effect of Drugs on Myocardial Hypoxia
    Garrett Gross; Fiscal Year: 2009
    ..Information gained from these studies will hopefully lead to new therapies to treat patients with ischemic heart disease. ..
  18. Molecular Physiology of Voltage gated Ion Channels
    Richard Horn; Fiscal Year: 2005
    ..The goals are to determine orientations of voltage sensors and gates with respect to surrounding regions of the channel and to see how these orientations change in response to changes of membrane potential. ..
  19. Nitric Oxide Regulation of Adrenal Steroidogenesis
    William Campbell; Fiscal Year: 2004
    ..4) We will determine the role of endothelial NO in regulating steroidogenesis and adrenal blood flow in the in situ perfused adrenal gland and in vivo in anesthetized rats. ..
  20. Regulation and actions of NO in the cardiac plexus
    JEAN HARDWICK; Fiscal Year: 2005
    ..In particular, it will provide important information concerning the regulation and of NO in the control of cardiac function. ..
  21. HYPERTENSION: CONTRIBUTION OF ARTERIAL WALL CHANGES
    Robert Cox; Fiscal Year: 2007
    ..These studies will define a novel therapeutic target for antihypertensive drug development based upon the mechanism(s) of Ca2+-Kv channel modulation. ..
  22. THE ROLE OF RETINOIDS IN LACRIMAL GLAND FUNCTION
    John Ubels; Fiscal Year: 2002
    ..abstract_text> ..
  23. EICOSANOIDS, VASCULAR TONE AND BLOOD PRESSURE
    WILLIAM BRYSON CAMPBELL; Fiscal Year: 2010
    ..These studies will test the hypothesis that endogenous LO metabolites are important regulators of vascular tone and blood pressure in mice. ..
  24. NERVE REPAIR BY SYNTHETIC AND BIOLOGICAL POLYMERS
    Riyi Shi; Fiscal Year: 2003
    ..Frequent consultation with a neurosurgeon, who is a member of the research team, will provide necessary input to direct the study and experiments towards clinically relevant solutions for transection nerve injuries. ..
  25. Elevated potassium ion in lacrimal fluid and the health of the ocular surface
    John Ubels; Fiscal Year: 2009
    ..If the high potassium in tears is important for the health of the ocular surface, this information will be useful in the development of improved treatments for dry eye disease. ..
  26. Molecular Physiology of Voltage-gated Ion Channels
    Richard Horn; Fiscal Year: 2009
    ..The proposed studies should help in the design of therapeutic drugs to treat a variety of malfunctions in excitability. ..
  27. MECHANISMS OF PERMEATION IN INWARD RECTIFIER K+ CHANNELS
    Zhe Lu; Fiscal Year: 2002
    ..For example, G-protein gated inward-rectifier K+ channels mediate the regulation of heart rate by vagal nerve, and ATP-sensitive inward-rectifier K+ channels are important during cardiac ischemia. (End of Abstract) ..
  28. LC-MS/MS for Biomedical Research
    William Campbell; Fiscal Year: 2004
    ..About 75-80% of instrument time will be available to these participants and the remaining time will be available to other investigators at the College. ..
  29. Analysis of Lacrimal Gland by Laser Microdissection
    John Ubels; Fiscal Year: 2003
    ..abstract_text> ..
  30. EICOSANOID SYNTHESIS AND FUNCTION IN CORONARY VESSELS
    WILLIAM BRYSON CAMPBELL; Fiscal Year: 2010
    ..These studies will provide specific pharmacological tools to study the role of EETs as EDHFs and provide new insights into the vascular action of the EETs. ..
  31. EDHF in the Cerebral Circulation
    ROBERT BRYAN; Fiscal Year: 2009
    ..Furthermore, we anticipate that new information regarding tandem pore domain potassium channels will be a big step in the understanding of cerebral circulatory control. ..
  32. Developmental Neuroscience Research Program
    PETER MACLEISH; Fiscal Year: 2007
    ..abstract_text> ..
  33. Gaq modulation of neuronal K+ channels: novel mechanisms and targets
    Douglas A Bayliss; Fiscal Year: 2011
    ..These experiments will characterize molecular substrates underlying native neuronal neurotransmitter-modulated background K+ currents and examine molecular mechanisms by which they are modulated. ..
  34. The Mitochondrial ATP-Sensitive K+ Channel in Heart
    Keith D Garlid; Fiscal Year: 2010
    ..Identification of signaling intermediates will utilize 32P-labeling and functional assays of phosphorylation. ..
  35. Collicular influence on auditory thalamic neurons
    Philip Smith; Fiscal Year: 2009
    ..The proposed experiments will help to answer these questions. ..
  36. Identification of compounds that protect HERG from block by proarrhythmic agents
    Sabina Kupershmidt; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  37. Prenatal Cocaine Exposure and Cardiac Programming
    Lubo Zhang; Fiscal Year: 2009
    ..abstract_text> ..
  38. Molecular Organization or Renal Organic Anion Transport
    Stephen H Wright; Fiscal Year: 2010
    ..abstract_text> ..
  39. Functional G Protein pathways in platelet activation
    Satya P Kunapuli; Fiscal Year: 2010
    ..These studies will enhance our understanding of the signaling pathways and their role in platelet activation, and might identify potential newer targets for the treatment of thrombosis. ..
  40. Vanderbilt Screen Center- GPCRs, Ion Channels, and(RMI)
    C Weaver; Fiscal Year: 2008
    ..abstract_text> ..
  41. GABA Signaling in the Postnatal Subventricular Zone
    Angelique Bordey; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  42. Platelet ADP receptors
    Satya Kunapuli; Fiscal Year: 2008
    ..We further propose to evaluate the relative contribution of the P2Y1 and the P2Y12 receptors to thrombus formation, using P2Y1 or P2Y12 deficient mice and treatment with antagonists and models of in vivo thrombosis and thromboembolism. ..
  43. MYOCARDIAL ENERGY METABOLISM IN THE DYSFUNCTIONAL LV
    Jianyi Zhang; Fiscal Year: 2003
    ..contributes to the transition between stable remodeling and CHF and, iii. Whether a metabolic intervention can attenuate the remodeling response and the transition from stable remodeling to CHF. ..
  44. Characterization of GAD67-GFP Transgenic Mice
    Ariel Agmon; Fiscal Year: 2003
    ..abstract_text> ..
  45. TRAINING PROGRAM IN MOLECULAR NEUROPHYSIOLOGY
    Frederick Sigworth; Fiscal Year: 2003
    ..The program offers an environment for intellectual breadth and collaboration, as well as training in the professional and ethical conduct of research. ..
  46. Cocaine and Apoptosis in the Developing Heart
    Lubo Zhang; Fiscal Year: 2004
    ..Such an understanding has obvious clinical implications because the increasing information has pointed to an important role of apoptosis in cardiovascular diseases. ..
  47. Stem cell patch therapy in hearts with LV infarction
    Jianyi Zhang; Fiscal Year: 2004
    ..By providing insight into the effects of the cellular patch transplantation, the results may lead to better preventive, diagnostic and therapeutic modalities for LV injury. ..
  48. Pathophysiology of glia following traumatic brain injury
    RAIMONDO D AMBROSIO; Fiscal Year: 2005
    ..Investigations on these post-traumatic changes will allow a more rational treatment to TBI. ..
  49. SIGNALING BY VASOPRESSIN--ARTERIAL SMOOTH MUSCLE CELLS
    KENNETH BYRON; Fiscal Year: 2002
    ..Finally, the effects of AVP and other hormones on [Ca2+]i and membrane currents will be examined in freshly isolated smooth muscle cells from rat mesenteric arteries. ..
  50. PRECURSOR CELL RENEWAL, OLIGODENDROCYTES & REMYELINATION
    Mark Noble; Fiscal Year: 2001
    ....
  51. MOLECULAR AND CELLULAR PHYSIOLOGY OF EPISODIC ATAXIA
    James Maylie; Fiscal Year: 2006
    ..The use of transgenic technology to develop mouse models of disease will permit an understanding of EA1 and the possibility of new pharmacological treatments for this disease. ..
  52. Cannabinoids and Central Neuronal Activity
    Paul Schweitzer; Fiscal Year: 2005
    ..abstract_text> ..
  53. Defective trafficking Mechanisms in a Cardiac K+ Channel
    Sabina Kupershmidt; Fiscal Year: 2006
    ..We will develop novel therapeutic strategies designed to correct intracellular processing steps of HERG and possibly other plasma membrane proteins that suffer from defects caused by the same mechanism. ..
  54. Vascular KATP Channel Modulation in Hypercapnic Acidosis
    Chun Jiang; Fiscal Year: 2006
    ..abstract_text> ..
  55. CEREBROVASCULAR ION CHANNELS IN HYPERTENSION
    J Marc Simard; Fiscal Year: 2007
    ..abstract_text> ..
  56. Reactive astrocytes from gliotic capsule
    J Marc Simard; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  57. Retinal Inhibitory Glycine Receptors
    Malcolm Slaughter; Fiscal Year: 2007
    ..Another is to characterize GABA receptor antagonists which interact with the glycine receptor. These specific aims are a necessary first step in unraveling inhibitory synapses in retina. ..
  58. Role of NTS POMC neurons in energy homeostasis
    SUZANNE APPLEYARD; Fiscal Year: 2008
    ..abstract_text> ..
  59. Reactive Oxygen Species American Society of Nephrology Fall 2007
    THOMAS PALLONE; Fiscal Year: 2007
    ..Attendance of young scientists insures that the information will be translated into future studies that elucidate the role of ROS in kidney diseases and treatment thereof. [unreadable] [unreadable] [unreadable]..
  60. New Technologies for Patch-Clamp Recording
    Frederick Sigworth; Fiscal Year: 2002
    ..The proposed simplification of the patch-clamp technique will have far-reaching benefits in the search for ion channel and transporter genes and in the discovery of new pharmacological agents. ..
  61. TRPM4 Channels in the Control of Cerebral Artery Tone
    Scott Earley; Fiscal Year: 2005
    ..It is anticipated that these studies will generate significant new information regarding the role of mechanosensitive cation channels in the regulation of VSM membrane potential and the regulation of cerebral blood flow. ..
  62. DEVELOPMENTAL REGULATION OF O2 SENSING IN THE LUNG
    David Cornfield; Fiscal Year: 2009
    ..The strategy of modulating BKCa channel subunit expression to enhance pulmonary vasodilation may be more broadly applicable to other vascular diseases. ..
  63. PURINERGIC AXIS OF CARDIAC BLOOD VESSELS
    IAIN BUXTON; Fiscal Year: 2001
    ..We will approach these aims with biochemical, pharmacological, molecular, cell biological and microscopic methods employing intact blood vessels, cells in primary culture and subcellular fractions. ..