MICHAEL CRAIG SANGUINETTI

Summary

Affiliation: University of Utah
Country: USA

Publications

  1. pmc ICA-105574 interacts with a common binding site to elicit opposite effects on inactivation gating of EAG and ERG potassium channels
    Vivek Garg
    Nora Eccles Harrison Cardiovascular Research and Training Institute, Department of Physiology, University of Utah, Salt Lake City, Utah 84112, USA
    Mol Pharmacol 83:805-13. 2013
  2. pmc Structure-activity relationship of fenamates as Slo2.1 channel activators
    Priyanka Garg
    Nora Eccles Harrison Cardiovascular Research and Training Institute, Department of Physiology, University of Utah, Salt Lake City, Utah 84112, USA
    Mol Pharmacol 82:795-802. 2012
  3. ncbi request reprint 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
  4. pmc A highly conserved alanine in the S6 domain of the hERG1 K+ channel is required for normal gating
    Scott Brown
    Department of Physiology, Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT 84112, USA
    Cell Physiol Biochem 22:601-10. 2008
  5. pmc HERG1 channelopathies
    Michael C Sanguinetti
    Department of Physiology, Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, 95 South 2000 East, Salt Lake, UT 84112, USA
    Pflugers Arch 460:265-76. 2010
  6. ncbi request reprint 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
  7. pmc Position of aromatic residues in the S6 domain, not inactivation, dictates cisapride sensitivity of HERG and eag potassium channels
    Jun Chen
    Department of Internal Medicine, University of Utah, 15 North 2030 East, Room 4220, Salt Lake City, UT 84112, USA
    Proc Natl Acad Sci U S A 99:12461-6. 2002
  8. ncbi request reprint Pharmacological activation of normal and arrhythmia-associated mutant KCNQ1 potassium channels
    Guiscard Seebohm
    Department of Physiology and Eccles Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, Utah 84112, USA
    Circ Res 93:941-7. 2003
  9. pmc Tight coupling of rubidium conductance and inactivation in human KCNQ1 potassium channels
    Guiscard Seebohm
    Department of Physiology, University of Utah, Salt Lake City, UT USA, Physiologisches Institut I, Tubingen, Germany
    J Physiol 552:369-78. 2003
  10. pmc PD-118057 contacts the pore helix of hERG1 channels to attenuate inactivation and enhance K+ conductance
    Matthew Perry
    Department of Physiology, bNora Eccles Harrison Cardiovascular Research and Training Institute, and cDepartment of Bioengineering, University of Utah, Salt Lake City, UT 84112, USA
    Proc Natl Acad Sci U S A 106:20075-80. 2009

Research Grants

  1. Modulation of cardiac K+ channels by drugs
    Michael Sanguinetti; Fiscal Year: 2007
  2. MOLECULAR MECHANISMS OF PACEMAKER CHANNEL FUNCTION
    Michael Sanguinetti; Fiscal Year: 2007
  3. Modulation of cardiac K+ channels by drugs
    Michael Sanguinetti; Fiscal Year: 2004
  4. MOLECULAR MECHANISMS OF PACEMAKER CHANNEL FUNCTION
    Michael Sanguinetti; Fiscal Year: 2003
  5. MODULATION OF CLASS III ANTIARRHYTHMIC DRUG EFFECTS
    Michael Sanguinetti; Fiscal Year: 2000
  6. Modulation of cardiac K+ channels by drugs
    MICHAEL CRAIG SANGUINETTI; Fiscal Year: 2010

Collaborators

Detail Information

Publications57

  1. pmc ICA-105574 interacts with a common binding site to elicit opposite effects on inactivation gating of EAG and ERG potassium channels
    Vivek Garg
    Nora Eccles Harrison Cardiovascular Research and Training Institute, Department of Physiology, University of Utah, Salt Lake City, Utah 84112, USA
    Mol Pharmacol 83:805-13. 2013
    ..The resultant agonist or antagonist activity is determined solely by channel-specific differences in the mechanisms of inactivation gating...
  2. pmc Structure-activity relationship of fenamates as Slo2.1 channel activators
    Priyanka Garg
    Nora Eccles Harrison Cardiovascular Research and Training Institute, Department of Physiology, University of Utah, Salt Lake City, Utah 84112, USA
    Mol Pharmacol 82:795-802. 2012
    ..Together, our results suggest that fenamates bind to two sites on Slo2.1 channels: an extracellular accessible site to activate and a cytoplasmic accessible site in the pore to inhibit currents...
  3. ncbi request reprint 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
    ..Insights gained from the crystal structures of other potassium channels have helped our understanding of the block of hERG channels and the mechanisms of gating...
  4. pmc A highly conserved alanine in the S6 domain of the hERG1 K+ channel is required for normal gating
    Scott Brown
    Department of Physiology, Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT 84112, USA
    Cell Physiol Biochem 22:601-10. 2008
    ..Thus, an Ala at position 653 in hERG1 is required for normal voltage dependence of channel gating and a charged residue in this position prevents channel closure...
  5. pmc HERG1 channelopathies
    Michael C Sanguinetti
    Department of Physiology, Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, 95 South 2000 East, Salt Lake, UT 84112, USA
    Pflugers Arch 460:265-76. 2010
    ..In addition, up-regulation of hERG1 channel expression has been demonstrated in specific tumors and has been associated with skeletal muscle atrophy in mice...
  6. ncbi request reprint 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...
  7. pmc Position of aromatic residues in the S6 domain, not inactivation, dictates cisapride sensitivity of HERG and eag potassium channels
    Jun Chen
    Department of Internal Medicine, University of Utah, 15 North 2030 East, Room 4220, Salt Lake City, UT 84112, USA
    Proc Natl Acad Sci U S A 99:12461-6. 2002
    ..These findings suggest that positioning of S6 aromatic residues relative to the central cavity of the channel, not inactivation per se determines drug block of HERG or eag channels...
  8. ncbi request reprint Pharmacological activation of normal and arrhythmia-associated mutant KCNQ1 potassium channels
    Guiscard Seebohm
    Department of Physiology and Eccles Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, Utah 84112, USA
    Circ Res 93:941-7. 2003
    ..Most KCNQ1 mutant channels responded to R-L3 similarly to wild-type channels, but one mutant channel (G306R) was insensitive to R-L3 possibly because it disrupted a key component of the drug-binding site...
  9. pmc Tight coupling of rubidium conductance and inactivation in human KCNQ1 potassium channels
    Guiscard Seebohm
    Department of Physiology, University of Utah, Salt Lake City, UT USA, Physiologisches Institut I, Tubingen, Germany
    J Physiol 552:369-78. 2003
    ....
  10. pmc PD-118057 contacts the pore helix of hERG1 channels to attenuate inactivation and enhance K+ conductance
    Matthew Perry
    Department of Physiology, bNora Eccles Harrison Cardiovascular Research and Training Institute, and cDepartment of Bioengineering, University of Utah, Salt Lake City, UT 84112, USA
    Proc Natl Acad Sci U S A 106:20075-80. 2009
    ..We conclude that direct interaction of PD-118057 with the pore helix attenuates fast P-type inactivation and increases open probability of hERG1 channels...
  11. pmc Novel KChIP2 isoforms increase functional diversity of transient outward potassium currents
    Niels Decher
    Department of Physiology, Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, 95 N 2000 E, Salt Lake City, UT 84112, USA
    J Physiol 557:761-72. 2004
    ..The biophysical changes induced by these alternatively spliced KChIP2 proteins differ markedly from previously described KChIP2 proteins and would be expected to increase the diversity of native transient outward K(+) currents...
  12. ncbi request reprint Compound mutations: a common cause of severe long-QT syndrome
    Peter Westenskow
    Department of Physiology, University of Utah, 95 South 2000 East, Salt Lake City, UT 84112 5000, USA
    Circulation 109:1834-41. 2004
    ..Although most LQTS individuals do not have cardiac events, significant phenotypic variability exists within families. Probands can be very symptomatic. The mechanism of this phenotypic variability is not understood...
  13. ncbi request reprint Physicochemical features of the HERG channel drug binding site
    David Fernandez
    Department of Physiology and Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, Utah 84112, USA
    J Biol Chem 279:10120-7. 2004
    ..Together, these findings assign specific residues to receptor fields predicted by pharmacophore models of hERG channel blockers and provide a refined molecular understanding of the drug binding site...
  14. pmc Structural basis of action for a human ether-a-go-go-related gene 1 potassium channel activator
    Matthew Perry
    Nora Eccles Harrison Cardiovascular Research and Training Institute and Department of Physiology, University of Utah, 95 South 2000 East, Salt Lake City, UT 84112, USA
    Proc Natl Acad Sci U S A 104:13827-32. 2007
    ..These findings define a putative binding site for RPR and confirm the importance of an interaction between the S4-S5 linker and the S6 domain in electromechanical coupling of voltage-gated K(+) channels...
  15. ncbi request reprint Molecular determinants of KCNQ1 channel block by a benzodiazepine
    Guiscard Seebohm
    Department of Physiology, University of Utah, Salt Lake City, USA
    Mol Pharmacol 64:70-7. 2003
    ....
  16. ncbi request reprint Molecular mapping of the binding site for a blocker of hyperpolarization-activated, cyclic nucleotide-modulated pacemaker channels
    Lan Cheng
    Department of Physiology, Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, 95 South 2000 East, Salt Lake City, UT 84112, USA
    J Pharmacol Exp Ther 322:931-9. 2007
    ....
  17. pmc A single amino acid difference between ether-a-go-go- related gene channel subtypes determines differential sensitivity to a small molecule activator
    Matthew Perry
    Nora Eccles Harrison Cardiovascular Research and Training Institute, Department of Physiology, University of Utah, 95 South 2000 East, Salt Lake City, UT 84112, USA
    Mol Pharmacol 73:1044-51. 2008
    ..A Thr in this position favors agonist activity, whereas an Ile reveals a secondary blocking effect of RPR...
  18. pmc Activation of Slo2.1 channels by niflumic acid
    Li Dai
    Department of Physiology, Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT 84112, USA
    J Gen Physiol 135:275-95. 2010
    ..Collectively, these findings indicate that Slo2.1 channel gating is modulated by [K(+)](e) and [Na(+)](e), and that NFA uncouples channel activation from its modulation by transmembrane voltage and intracellular Na(+)...
  19. pmc Binding site of a novel Kv1.5 blocker: a "foot in the door" against atrial fibrillation
    Niels Decher
    Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, 95 South 2000 East, Salt Lake City, UT 84112, USA
    Mol Pharmacol 70:1204-11. 2006
    ..This "foot-in-the-door" binding mode is consistent with the observation that the drug slowed the rate of current deactivation, causing a crossover of tail current traces recorded before and after drug treatment...
  20. ncbi request reprint Voltage-dependent gating of hyperpolarization-activated, cyclic nucleotide-gated pacemaker channels: molecular coupling between the S4-S5 and C-linkers
    Niels Decher
    Department of Physiology and Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, Utah 84112 5000, USA
    J Biol Chem 279:13859-65. 2004
    ....
  21. ncbi request reprint Impaired interaction between the slide helix and the C-terminus of Kir2.1: a novel mechanism of Andersen syndrome
    Niels Decher
    Nora Eccles Harrison CVRTI and Department of Physiology, University of Utah, Salt Lake City, UT 84112, USA
    Cardiovasc Res 75:748-57. 2007
    ..We identified two unrelated patients with mutations in the slide helix of Kir2.1 leading to AS. The functional consequences of these two mutations, Y68D and D78Y, were studied and compared with previously reported slide helix mutations...
  22. ncbi request reprint Structural basis for competition between drug binding and Kvbeta 1.3 accessory subunit-induced N-type inactivation of Kv1.5 channels
    Niels Decher
    Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT 84112, USA
    Mol Pharmacol 68:995-1005. 2005
    ..3 but not in the presence of an N-truncated form of the Kvbeta subunit. Thus, residues in the pore of Kv1.5 required for N-type inactivation overlap with but are not identical to the drug binding site...
  23. ncbi request reprint Voltage sensing and activation gating of HCN pacemaker channels
    Jun Chen
    Department of Medicine, Division of Cardiology and Eccles Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, UT 84112 5330, USA
    Trends Cardiovasc Med 12:42-5. 2002
    ..However, unlike most other channels channel, opening occurs in response to membrane hyperpolarization rather than depolarization...
  24. ncbi request reprint KCNQ2 and KCNQ3 potassium channel genes in benign familial neonatal convulsions: expansion of the functional and mutation spectrum
    Nanda A Singh
    Department of Human Genetics, University of Utah, Salt Lake City, Utah 84112, USA
    Brain 126:2726-37. 2003
    ..We report here the first dominant negative mutation in KCNQ2 that has a phenotype of neonatal seizures without permanent clinical CNS impairment...
  25. pmc Molecular mapping of a site for Cd2+-induced modification of human ether-à-go-go-related gene (hERG) channel activation
    David Fernandez
    Department of Physiology, University of Utah, Salt Lake City, 84112 5000, USA
    J Physiol 567:737-55. 2005
    ..5,act). Extracellular Cd(2+) modulates hERG channel activation by binding to a coordination site formed, at least in part, by three Asp residues...
  26. doi request reprint Cooperative interactions between R531 and acidic residues in the voltage sensing module of hERG1 channels
    David R Piper
    Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT 84113, USA
    Cell Physiol Biochem 21:37-46. 2008
    ..We propose that hERG1 activation involves a cooperative conformational change involving the entire voltage sensing module, while inactivation may involve a more limited interaction between R531 and D456, D460 and D509...
  27. ncbi request reprint 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...
  28. pmc Structural basis for ether-a-go-go-related gene K+ channel subtype-dependent activation by niflumic acid
    David Fernandez
    Nora Eccles Harrison Cardiovascular Research and Training Institute, Department of Physiology, University of Utah, 95 South 2000 East, Salt Lake City, UT 84112, USA
    Mol Pharmacol 73:1159-67. 2008
    ..The molecular determinants of enhanced sensitivity of ERG2 channels to NFA were isolated to an Arg and a Thr triplet in the extracellular S3-S4 linker...
  29. pmc Mechanisms by which atrial fibrillation-associated mutations in the S1 domain of KCNQ1 slow deactivation of IKs channels
    Lioara Restier
    Nora Eccles Harrison Cardiovascular Research and Training Institute and Department of Physiology, University of Utah, Salt Lake City, UT 84112, USA
    J Physiol 586:4179-91. 2008
    ..Together our findings suggest that altered charge-pair interactions within the voltage sensor module of KCNQ1 subunits may account for slowed I(Ks) deactivation induced by S140 or V141...
  30. ncbi request reprint Regional specificity of human ether-a'-go-go-related gene channel activation and inactivation gating
    David R Piper
    Department of Physiology, Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, Utah 84112, USA
    J Biol Chem 280:7206-17. 2005
    ..These results define regions on the S4 voltage sensor that contribute differentially to hERG activation and inactivation gating...
  31. ncbi request reprint Structural determinants and biophysical properties of HERG and KCNQ1 channel gating
    Martin Tristani-Firouzi
    Department of Pediatrics, Pediatric Cardiology, Suite 1500 PCMC, University of Utah School of Medicine, 100 N Medical Drive, Salt Lake City, UT 84113, USA
    J Mol Cell Cardiol 35:27-35. 2003
    ..This review summarizes the current state of knowledge regarding the structural determinants and biophysical properties of HERG and KCNQ1 channels...
  32. pmc Gating currents associated with intramembrane charge displacement in HERG potassium channels
    David R Piper
    Department of Physiologyetics, University of Utah, Salt Lake City, UT 84112, USA
    Proc Natl Acad Sci U S A 100:10534-9. 2003
    ..Analysis of an inactivation-deficient mutant HERG channel and a Markov kinetic model suggest that HERG inactivation is coupled to activation...
  33. ncbi request reprint Antiarrhythmic drug target choices and screening
    Michael C Sanguinetti
    Department of Physiology, Eccles Institute of Human Genetics, University of Utah, 15 N 2030 E, Room 4220, Salt Lake City, UT 84112, USA
    Circ Res 93:491-9. 2003
    ..Here, we briefly review the multiple mechanisms of arrhythmia, the history of drug failures, and the possibilities that evolving technologies may provide in the search for more efficacious and safer antiarrhythmic drugs...
  34. ncbi request reprint 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...
  35. ncbi request reprint Voltage sensor movement in the hERG K+ channel
    David R Piper
    Department of Physiology, University of Utah, Salt Lake City, UT 84113, USA
    Novartis Found Symp 266:46-52; discussion 52-6, 95-9. 2005
    ..We conclude that S4 acts as the voltage sensor for hERG activation and inactivation and that S4 movement is translated to the activation gate via the S4-S5 linker...
  36. pmc Niflumic acid alters gating of HCN2 pacemaker channels by interaction with the outer region of S4 voltage sensing domains
    Lan Cheng
    Nora Eccles Harrison Cardiovascular Research and Training Institute, Department of Physiology, University of Utah, Salt Lake City, UT 84112, USA
    Mol Pharmacol 75:1210-21. 2009
    ..We conclude that NFA alters HCN2 gating by interacting with the extracellular end of the S4 voltage sensor domains...
  37. ncbi request reprint Physicochemical basis for binding and voltage-dependent block of hERG channels by structurally diverse drugs
    Michael C Sanguinetti
    Department of Physiology, Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, USA
    Novartis Found Symp 266:159-66; discussion 166-70. 2005
    ....
  38. pmc Structural determinants of Kvbeta1.3-induced channel inactivation: a hairpin modulated by PIP2
    Niels Decher
    Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, USA
    EMBO J 27:3164-74. 2008
    ..Taken together, our findings indicate that inactivation of Kv1.5 is mediated by an equilibrium binding of the N terminus of Kvbeta1.3 between phosphoinositides (PIPs) and the inner pore region of the channel...
  39. pmc Modification of hERG1 channel gating by Cd2+
    Jennifer Abbruzzese
    Department of Physiology, University of Utah, Salt Lake City, UT 84112, USA
    J Gen Physiol 136:203-24. 2010
    ..New Markov models of hERG1 channels were developed that describe gating currents as a noncooperative two-phase process of the VSD and can account for changes in these currents caused by extracellular Cd(2+)...
  40. pmc Mechanism of action of a novel human ether-a-go-go-related gene channel activator
    Oscar Casis
    Nora Eccles Harrison Cardiovascular Research and Training Institute and Department of Physiology, University of Utah, Salt Lake City, 84112, USA
    Mol Pharmacol 69:658-65. 2006
    ..We conclude that NS1643 is a partial agonist of hERG channels and that the mechanism of activation is reduced channel inactivation...
  41. pmc Molecular determinants for activation of human ether-à-go-go-related gene 1 potassium channels by 3-nitro-n-(4-phenoxyphenyl) benzamide
    Vivek Garg
    Department of Physiology, Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, Utah, USA
    Mol Pharmacol 80:630-7. 2011
    ..Activation or inhibition of currents is mediated by the same or overlapping binding site located in the pore module between two adjacent subunits of the homotetrameric channel...
  42. ncbi request reprint Molecular determinants of voltage-dependent human ether-a-go-go related gene (HERG) K+ channel block
    Jose A Sanchez-Chapula
    Unidad de Investigación Carlos Méndez del Centro Universitario de Investigaciones Biomédicas de la Universidad de Colima, 23000 Colima, Mexico
    J Biol Chem 277:23587-95. 2002
    ..Our experimental findings and modeling suggest that chloroquine preferentially blocks open HERG channels by cation-pi and pi-stacking interactions with Tyr-652 and Phe-656 of multiple subunits...
  43. ncbi request reprint Voltage-dependent profile of human ether-a-go-go-related gene channel block is influenced by a single residue in the S6 transmembrane domain
    Jose A Sanchez-Chapula
    Unidad de Investigación Carlos Méndez del Centro Universitario de Investigaciones Biomédicas de la Universidad de Colima, Colima, Mexico
    Mol Pharmacol 63:1051-8. 2003
    ....
  44. ncbi request reprint Reduced transient outward K+ current and cardiac hypertrophy: causal relationship or epiphenomenon?
    Michael C Sanguinetti
    Circ Res 90:497-9. 2002
  45. ncbi request reprint Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism
    Igor Splawski
    Department of Cardiology, Children s Hospital, Harvard Medical School and Howard Hughes Medical Institute, Boston, MA 02115, USA
    Cell 119:19-31. 2004
    ..These discoveries establish the importance of Ca(V)1.2 in human physiology and development and implicate Ca(2+) signaling in autism...
  46. ncbi request reprint Structural determinants of HERG channel block by clofilium and ibutilide
    Matthew Perry
    University of Leicester, Department of Cell Physiology and Pharmacology, United Kingdom
    Mol Pharmacol 66:240-9. 2004
    ..g., clofilium) or a methanesulfonamide (e.g., ibutilide)...
  47. ncbi request reprint Block of wild-type and inactivation-deficient human ether-a-go-go-related gene K+ channels by halofantrine
    Jose A Sanchez-Chapula
    Unidad de Investigación Carlos Méndez del Centro Universitario de Investigaciones, Biomédicas de la Universidad de Colima, Av 25 de Julio 965, Col Villa San Sebastian, 28045 Colima, Mexico
    Naunyn Schmiedebergs Arch Pharmacol 370:484-91. 2004
    ..We conclude that halofantrine requires channels to open before it can gain access to its binding site located in the central cavity of the HERG channel...
  48. pmc Mutation of colocalized residues of the pore helix and transmembrane segments S5 and S6 disrupt deactivation and modify inactivation of KCNQ1 K+ channels
    Guiscard Seebohm
    Department of Physiology I, Universität Tuebingen, Gmelinstr 5, D 72076 Tuebingen, Germany
    J Physiol 563:359-68. 2005
    ..Disturbance of these interactions might underly LQTS associated with KCNQ1 mutant channels...
  49. pmc Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations
    Igor Splawski
    Howard Hughes Medical Institute, Department of Cardiology, and Genomics Program and Division of Genetics, Children s Hospital, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 102:8089-96; discussion 8086-8. 2005
    ..These data indicate that gain-of-function mutations of CaV1.2 exons 8 and 8A cause distinct forms of TS...
  50. ncbi request reprint Structural determinants for high-affinity block of hERG potassium channels
    John Mitcheson
    Department of Cell Physiology and Pharmacology, University of Leicester, University Road, Leicester LE1 9HN, UK
    Novartis Found Symp 266:136-50; discussion 150-8. 2005
    ..Ser624 and Thr623 residues at the base of the pore helices are also critical for high-affinity binding for some compounds (e.g. methanesulfonanilides) but not others (cisapride, terfenadine, propafenone)...
  51. ncbi request reprint De novo KCNQ1 mutation responsible for atrial fibrillation and short QT syndrome in utero
    Kui Hong
    Masonic Medical Research Laboratory, Utica, NY, USA
    Cardiovasc Res 68:433-40. 2005
    ..We describe a genetic basis for atrial fibrillation and short QT syndrome in utero. Heterologous expression of the mutant channel was used to define the physiological consequences of the mutation...
  52. pmc Molecular determinants of HERG channel block
    Kaichiro Kamiya
    Department of Humoral Regulation, Research Institute of Environmental Medicine, Nagoya University, Japan
    Mol Pharmacol 69:1709-16. 2006
    ..We conclude that the binding site is not identical for all drugs that preferentially block hERG in the open state...
  53. pmc Differential roles of S6 domain hinges in the gating of KCNQ potassium channels
    Guiscard Seebohm
    Physiologisches Institut I, Universitat Tubingen, D 72076 Tubingen, Germany
    Biophys J 90:2235-44. 2006
    ....
  54. pmc Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death
    Charles Antzelevitch
    Masonic Medical Research Laboratory, 2150 Bleecker St, Utica, NY 13501, USA
    Circulation 115:442-9. 2007
    ..We describe a new clinical entity that consists of an ST-segment elevation in the right precordial ECG leads, a shorter-than-normal QT interval, and a history of sudden cardiac death...
  55. ncbi request reprint Regulation of endocytic recycling of KCNQ1/KCNE1 potassium channels
    Guiscard Seebohm
    Department of Physiology I, University of Tuebingen, Gmelinstrasse 5, D 72076 Tuebingen, Germany
    Circ Res 100:686-92. 2007
    ....
  56. ncbi request reprint When the KChIPs are down
    Michael C Sanguinetti
    Nat Med 8:18-9. 2002
  57. ncbi request reprint International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels
    George A Gutman
    Department of Microbiology and Molecular Genetics, University of California, Irvine, CA, USA
    Pharmacol Rev 57:473-508. 2005

Research Grants19

  1. Modulation of cardiac K+ channels by drugs
    Michael Sanguinetti; Fiscal Year: 2007
    ..In Aim 3, we will determine the binding site and molecular basis of altered gating induced by two hERG channel activators, a fenamate and a novel quinolinylpiperidine. ..
  2. MOLECULAR MECHANISMS OF PACEMAKER CHANNEL FUNCTION
    Michael Sanguinetti; Fiscal Year: 2007
    ..These studies promise to further our understanding of the biological oscillator that controls heart rhythm. ..
  3. Modulation of cardiac K+ channels by drugs
    Michael Sanguinetti; Fiscal Year: 2004
    ..abstract_text> ..
  4. MOLECULAR MECHANISMS OF PACEMAKER CHANNEL FUNCTION
    Michael Sanguinetti; Fiscal Year: 2003
    ..These studies will elucidate the molecular mechanisms for gating of HCN channels and further our understanding of the cardiac pacemaker. ..
  5. MODULATION OF CLASS III ANTIARRHYTHMIC DRUG EFFECTS
    Michael Sanguinetti; Fiscal Year: 2000
    ..Our long term goal is to provide a mechanistic rationale for the design of class III antiarrhythmics that retain desired efficacy without undesirable rate-dependence or a propensity to induce EADs. ..
  6. Modulation of cardiac K+ channels by drugs
    MICHAEL CRAIG SANGUINETTI; Fiscal Year: 2010
    ..In Aim 3, we will determine the binding site and molecular basis of altered gating induced by two hERG channel activators, a fenamate and a novel quinolinylpiperidine. ..