Hcn2

Summary

Gene Symbol: Hcn2
Description: hyperpolarization-activated, cyclic nucleotide-gated K+ 2
Alias: BCNG2, HAC1, trls, potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2, BCNG-2, HAC-1, brain cyclic nucleotide-gated channel 2, hyperpolarization-activated cation channel 1
Species: mouse

Top Publications

  1. pmc Regulation of gating and rundown of HCN hyperpolarization-activated channels by exogenous and endogenous PIP2
    Phillip Pian
    Center for Neurobiology and Behavior, Columbia University Medical Center, New York, NY 10032, USA
    J Gen Physiol 128:593-604. 2006
  2. pmc Absence epilepsy in apathetic, a spontaneous mutant mouse lacking the h channel subunit, HCN2
    Wendy K Chung
    Division of Molecular Genetics and the Naomi Berrie Diabetes Center, Columbia University Medical College, Russell Berrie Medical Science Pavilion, Room 620, 1150 St Nicholas Avenue, New York, NY 10032, USA
    Neurobiol Dis 33:499-508. 2009
  3. ncbi Dendritic excitability of mouse frontal cortex pyramidal neurons is shaped by the interaction among HCN, Kir2, and Kleak channels
    Michelle Day
    Department of Physiology, Northwestern University Medical School, Chicago, Illinois 60611, USA
    J Neurosci 25:8776-87. 2005
  4. ncbi A novel mechanism of modulation of hyperpolarization-activated cyclic nucleotide-gated channels by Src kinase
    Xiangang Zong
    Department Pharmazie, Pharmakologie für Naturwissenschaften, Ludwig Maximilians Universitat Munchen, Butenandtstrasse 7, 81377 Munchen
    J Biol Chem 280:34224-32. 2005
  5. ncbi Compartmental distribution of hyperpolarization-activated cyclic-nucleotide-gated channel 2 and hyperpolarization-activated cyclic-nucleotide-gated channel 4 in thalamic reticular and thalamocortical relay neurons
    S Y Abbas
    C V Starr Laboratory for Molecular Neuropharmacology, Department of Anesthesiology, Weill Medical College of Cornell University, 1300 York Avenue, Room A 1050, New York, NY 10021, USA
    Neuroscience 141:1811-25. 2006
  6. ncbi Regulation of HCN channel surface expression by a novel C-terminal protein-protein interaction
    Bina Santoro
    Center for Neurobiology and Behavior, Columbia University, New York, New York 10032, USA
    J Neurosci 24:10750-62. 2004
  7. ncbi HCN2 and HCN1 channels govern the regularity of autonomous pacemaking and synaptic resetting in globus pallidus neurons
    C Savio Chan
    Department of Physiology and Institute for Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
    J Neurosci 24:9921-32. 2004
  8. ncbi HCN2 and HCN4 isoforms self-assemble and co-assemble with equal preference to form functional pacemaker channels
    Gina M Whitaker
    Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    J Biol Chem 282:22900-9. 2007
  9. pmc Gating of HCN channels by cyclic nucleotides: residue contacts that underlie ligand binding, selectivity, and efficacy
    Lei Zhou
    Center for Neurobiology and Behavior, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA
    Structure 15:655-70. 2007
  10. ncbi 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

Scientific Experts

  • Stefan Stoll
  • Hyunhyo Seo
  • Darrin H Brager
  • Stefan Herrmann
  • B Santoro
  • William Zagotta
  • F Elinder
  • Hans Ulrich Fried
  • A Ludwig
  • Bin Ye
  • Lucas Matt
  • Eric A Accili
  • Alan S Lewis
  • Dane M Chetkovich
  • Michael C Puljung
  • Vincenzo Macri
  • Xiangang Zong
  • Hannah A Deberg
  • Lei Zhou
  • C Savio Chan
  • Annalisa Bucchi
  • Guido Michels
  • Martin Biel
  • Damiano Angoli
  • Christian Wahl-Schott
  • Hamed Nazzari
  • Ryuichi Shigemoto
  • Gina M Whitaker
  • Richard B Robinson
  • Minyoung Shin
  • Koichiro Kuwahara
  • D James Surmeier
  • Niels Decher
  • Kensuke Oshita
  • Steven A Siegelbaum
  • Pavel Honsa
  • Catherine Proenza
  • Nabil El Khoury
  • Konstantin Wemhöner
  • John R Bankston
  • Shui Wang Ying
  • Luca Della Santina
  • Florian Hofmann
  • Neeliyath A Ramakrishnan
  • Ludwig Baumann
  • Geoffrey C Horwitz
  • Nadine L Wicks
  • J Chen
  • Edward C Emery
  • Shengjun Wu
  • Verena Hammelmann
  • Barbara Much
  • Andrew P Hegle
  • Arie S Mobley
  • Xin Zhao
  • Anjali O Rozario
  • Kazuwa Nakao
  • Makoto Takano
  • Patrick A Schweizer
  • Wendy K Chung
  • Franz Hofmann
  • Stylianos Michalakis
  • Jianying Huang
  • Yang Qu
  • Tatiana Tkatch
  • Sriharsha Vemana
  • Jeff N Mercer
  • Yelena Kryukova
  • Shan Chen
  • Kiyoko Hattori
  • Lan Cheng
  • Uta C Hoppe
  • Marco Berrera
  • Sven G Meuth
  • Phillip Pian
  • S Y Abbas
  • Michael C Sanguinetti
  • Michelle Day
  • Wilfried Mai
  • Biagio Gravante
  • Ezana M Azene
  • Peter S Brzovic
  • Galen E Flynn
  • Shingo Hirashima
  • Kei ichiro Nakamura
  • Keiko Ishihara
  • Takeshi Kimura
  • Kazuo Ushijima
  • Yoshihiro Kuwabara
  • Masayuki Itoh

Detail Information

Publications73

  1. pmc Regulation of gating and rundown of HCN hyperpolarization-activated channels by exogenous and endogenous PIP2
    Phillip Pian
    Center for Neurobiology and Behavior, Columbia University Medical Center, New York, NY 10032, USA
    J Gen Physiol 128:593-604. 2006
    ..bath application of exogenous PI(4,5)P(2) reverses the effect of rundown, producing a large depolarizing shift in HCN2 activation...
  2. pmc Absence epilepsy in apathetic, a spontaneous mutant mouse lacking the h channel subunit, HCN2
    Wendy K Chung
    Division of Molecular Genetics and the Naomi Berrie Diabetes Center, Columbia University Medical College, Russell Berrie Medical Science Pavilion, Room 620, 1150 St Nicholas Avenue, New York, NY 10032, USA
    Neurobiol Dis 33:499-508. 2009
    ..mouse, apathetic (ap/ap), and identified the ap mutation as a 4 base pair insertion within the coding region of Hcn2, the gene encoding the h channel subunit 2 (HCN2)...
  3. ncbi Dendritic excitability of mouse frontal cortex pyramidal neurons is shaped by the interaction among HCN, Kir2, and Kleak channels
    Michelle Day
    Department of Physiology, Northwestern University Medical School, Chicago, Illinois 60611, USA
    J Neurosci 25:8776-87. 2005
    ..experiments revealed the presence of rapidly activating and deactivating cationic currents attributable to HCN1/HCN2 channels...
  4. ncbi A novel mechanism of modulation of hyperpolarization-activated cyclic nucleotide-gated channels by Src kinase
    Xiangang Zong
    Department Pharmazie, Pharmakologie für Naturwissenschaften, Ludwig Maximilians Universitat Munchen, Butenandtstrasse 7, 81377 Munchen
    J Biol Chem 280:34224-32. 2005
    ..Immunoprecipitation demonstrated that Src binds to and phosphorylates native and heterologously expressed HCN2. Src interacts via its SH3 domain with a sequence of HCN2 encompassing part of the C-linker and the cyclic ..
  5. ncbi Compartmental distribution of hyperpolarization-activated cyclic-nucleotide-gated channel 2 and hyperpolarization-activated cyclic-nucleotide-gated channel 4 in thalamic reticular and thalamocortical relay neurons
    S Y Abbas
    C V Starr Laboratory for Molecular Neuropharmacology, Department of Anesthesiology, Weill Medical College of Cornell University, 1300 York Avenue, Room A 1050, New York, NY 10021, USA
    Neuroscience 141:1811-25. 2006
    ..HCN1-4) have been identified, and mRNAs and proteins for HCN channels have been detected in the RTN and VB, with HCN2 and HCN4 being the predominant isoforms...
  6. ncbi Regulation of HCN channel surface expression by a novel C-terminal protein-protein interaction
    Bina Santoro
    Center for Neurobiology and Behavior, Columbia University, New York, New York 10032, USA
    J Neurosci 24:10750-62. 2004
    ..Finally, TRIP8b expression in cultured pyramidal neurons markedly decreases native I(h) density. These data suggest a possible role for TRIP8b in regulating HCN channel density in the plasma membrane...
  7. ncbi HCN2 and HCN1 channels govern the regularity of autonomous pacemaking and synaptic resetting in globus pallidus neurons
    C Savio Chan
    Department of Physiology and Institute for Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
    J Neurosci 24:9921-32. 2004
    ..Single-cell RT-PCR and immunohistochemical approaches revealed robust expression of HCN2 subunits as well as significant levels of HCN1 subunits in GABAergic GP neurons...
  8. ncbi HCN2 and HCN4 isoforms self-assemble and co-assemble with equal preference to form functional pacemaker channels
    Gina M Whitaker
    Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    J Biol Chem 282:22900-9. 2007
    ..Previous studies have suggested that the HCN2 and HCN4 channel isoforms physically interact when overexpressed in mammalian cells, but whether they are able to ..
  9. pmc Gating of HCN channels by cyclic nucleotides: residue contacts that underlie ligand binding, selectivity, and efficacy
    Lei Zhou
    Center for Neurobiology and Behavior, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA
    Structure 15:655-70. 2007
    ..with mutagenesis to identify ligand contacts important for the regulation of the hyperpolarization-activated HCN2 channel by cNMPs...
  10. ncbi 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
    ..We previously reported that the mutation of specific residues in the S4-S5 linker of HCN2 (i.e...
  11. ncbi Structural basis for modulation and agonist specificity of HCN pacemaker channels
    William N Zagotta
    Department of Physiology and Biophysics, Howard Hughes Medical Institute, Box 357290, University of Washington School of Medicine, Seattle, Washington 98195 7290, USA
    Nature 425:200-5. 2003
    ..Here we have investigated the mechanism underlying this modulation by studying a carboxy-terminal fragment of HCN2 containing the cyclic nucleotide-binding domain (CNBD) and the C-linker region that connects the CNBD to the pore...
  12. ncbi Role of subunit heteromerization and N-linked glycosylation in the formation of functional hyperpolarization-activated cyclic nucleotide-gated channels
    Barbara Much
    Department Pharmazie Pharmakologie für Naturwissenschaften, Ludwig Maximilians Universitat Munchen, Butenandtstrasse 7, 81377 Munchen, Germany
    J Biol Chem 278:43781-6. 2003
    ..We also identified HCN1/HCN2 heteromers in mouse brain indicating that heteromeric channels exist in vivo...
  13. pmc Absence epilepsy and sinus dysrhythmia in mice lacking the pacemaker channel HCN2
    Andreas Ludwig
    Institut fur Pharmakologie und Toxikologie, Technische Universitat Munchen, D 80802 München, Germany
    EMBO J 22:216-24. 2003
    ..Here we show that HCN2-deficient mice exhibit spontaneous absence seizures...
  14. ncbi MinK-related peptide 1: A beta subunit for the HCN ion channel subunit family enhances expression and speeds activation
    H Yu
    Institute of Molecular Cardiology, Department of Physiology and Biophysics, Stony Brook, NY, USA
    Circ Res 88:E84-7. 2001
    ..The full text of this article is available at http://www.circresaha.org...
  15. pmc Interactive cloning with the SH3 domain of N-src identifies a new brain specific ion channel protein, with homology to eag and cyclic nucleotide-gated channels
    B Santoro
    Center for Neurobiology and Behavior, College of Physicians and Surgeons of Columbia University, and Howard Hughes Medical Institute, 722 West 168th Street, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 94:14815-20. 1997
    ..These findings suggest the existence of a new type of ion channel, which is potentially able to modulate membrane excitability in the brain and could respond to regulation by cyclic nucleotides...
  16. ncbi Functional roles of charged residues in the putative voltage sensor of the HCN2 pacemaker channel
    J Chen
    Department of Medicine, Division of Cardiology and Eccles Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, Utah 84112 5330, USA
    J Biol Chem 275:36465-71. 2000
    ....
  17. ncbi A family of hyperpolarization-activated mammalian cation channels
    A Ludwig
    Institut fur Pharmakologie und Toxikologie, Technische Universitat Munchen, Germany
    Nature 393:587-91. 1998
    ..the molecular cloning and functional expression of the gene encoding a hyperpolarization-activated cation channel (HAC1) that is present in brain and heart. This channel exhibits the general properties of Ih channels...
  18. ncbi Identification of a gene encoding a hyperpolarization-activated pacemaker channel of brain
    B Santoro
    Center for Neurobiology and Behavior, Columbia University, New York, New York 10032, USA
    Cell 93:717-29. 1998
    ....
  19. pmc Hyperpolarization-activated cyclic nucleotide-modulated 'HCN' channels confer regular and faster rhythmicity to beating mouse embryonic stem cells
    Yang Qu
    Cardiac Membrane Research Laboratory, Simon Fraser University, Burnaby, BC, Canada
    J Physiol 586:701-16. 2008
    ..together, the activation kinetics of I(f) and results from Western blots are consistent with the presence of the HCN2 and HCN3 isoforms...
  20. pmc Structure and Energetics of Allosteric Regulation of HCN2 Ion Channels by Cyclic Nucleotides
    Hannah A Deberg
    From the Departments of Chemistry, Physiology and Biophysics, and
    J Biol Chem 291:371-81. 2016
    ..We explain these results with a model where different allosteric mechanisms in the CNBD all converge to have the same effect on the C-linker and render all three cyclic nucleotides similarly potent activators of the channel. ..
  21. doi Novel insights into the distribution of cardiac HCN channels: an expression study in the mouse heart
    Stefan Herrmann
    Institut fur Experimentelle und Klinische Pharmakologie und Toxikologie, Friedrich Alexander Universitat Erlangen Nurnberg, Germany
    J Mol Cell Cardiol 51:997-1006. 2011
    ..The specificity of antibodies used was strictly confirmed by the use of HCN1, HCN2 and HCN4 knockout animals...
  22. pmc Double electron-electron resonance reveals cAMP-induced conformational change in HCN channels
    Michael C Puljung
    Departments of Physiology and Biophysics and
    Proc Natl Acad Sci U S A 111:9816-21. 2014
    ..These results provide a basis for understanding how the binding of cAMP is coupled to channel opening in HCN and related channels. ..
  23. doi Increased expression of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in reactive astrocytes following ischemia
    Pavel Honsa
    Department of Cellular Neurophysiology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague 4, 14220, Czech Republic
    Glia 62:2004-21. 2014
    ..Collectively, our results demonstrate that regardless of the type of ischemic injury, reactive astrocytes express HCN channels, which could therefore be an important therapeutic target in poststroke therapy...
  24. doi Ectopic automaticity induced in ventricular myocytes by transgenic overexpression of HCN2
    Kensuke Oshita
    Department of Physiology, Kurume University School of Medicine, Kurume, Japan Department of Anesthesiology, Kurume University School of Medicine, Kurume, Japan
    J Mol Cell Cardiol 80:81-9. 2015
    ..To test this hypothesis, we generated and analyzed transgenic mice overexpressing HCN2 specifically in their hearts (HCN2-Tg)...
  25. pmc Differential expression of hyperpolarization-activated cyclic nucleotide-gated channel subunits during hippocampal development in the mouse
    Hyunhyo Seo
    Department of Anatomy, Brain Science and Engineering Institute, Kyungpook National University Graduate School of Medicine, 2 101, Dongin Dong, Jung Gu, Daegu, 700 842, South Korea
    Mol Brain 8:13. 2015
    ..However, little is known about the timing and cell type specificity of the expression of HCN isoforms during development of the hippocampus...
  26. pmc Processing of retinal signals in normal and HCN deficient mice
    Luca Della Santina
    Department of Physiological Science, University of Pisa, Pisa, Italy
    PLoS ONE 7:e29812. 2012
    ..mice models and of in vitro (patch-clamp) and in vivo (ERG) recordings of retinal activity we show that HCN1 and HCN2 channels are expressed at distinct retinal sites and serve different functions...
  27. pmc The cGMP-dependent protein kinase II Is an inhibitory modulator of the hyperpolarization-activated HCN2 channel
    Verena Hammelmann
    Munich Center for Integrated Protein Science CIPSM, Ludwig Maximilians Universitat Munchen, Munchen, Germany
    PLoS ONE 6:e17078. 2011
    ..Here, we show for the first time that in the HCN2 channel cGMP can also exert an inhibitory effect on gating via cGMP-dependent protein kinase II (cGKII)-mediated ..
  28. pmc Structure and stoichiometry of an accessory subunit TRIP8b interaction with hyperpolarization-activated cyclic nucleotide-gated channels
    John R Bankston
    Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 109:7899-904. 2012
    ..Here we examine the molecular determinants of TRIP8b binding to HCN2 channels...
  29. doi Upregulation of the hyperpolarization-activated current increases pacemaker activity of the sinoatrial node and heart rate during pregnancy in mice
    Nabil El Khoury
    Research Center, Montreal Heart Institute, 5000 Belanger, Montreal, Quebec, Canada, H1T 1C8
    Circulation 127:2009-20. 2013
    ..However, the underlying mechanisms for this increased HR are poorly understood. Therefore, this study was performed to gain mechanistic insight into the pregnancy-induced increase in HR...
  30. pmc A secondary structural transition in the C-helix promotes gating of cyclic nucleotide-regulated ion channels
    Michael C Puljung
    Department of Physiology and Biophysics, University of Washington, Seattle, Washington 98195 7290, USA
    J Biol Chem 288:12944-56. 2013
    ..We monitored the cAMP-dependent changes in the structure of the C-helix of a C-terminal fragment of HCN2 channels using transition metal ion FRET between fluorophores on the C-helix and metal ions bound between histidine ..
  31. pmc A leucine zipper motif essential for gating of hyperpolarization-activated channels
    Konstantin Wemhöner
    Institute for Physiology, Vegetative Physiology Group, University of Marburg, Deutschhausstrasse 1 2, 35037 Marburg, Germany
    J Biol Chem 287:40150-60. 2012
    ..It is poorly understood how hyperpolarization-activated cyclic nucleotide-gated channels (HCNs) function...
  32. pmc HCN1 and HCN2 proteins are expressed in cochlear hair cells: HCN1 can form a ternary complex with protocadherin 15 CD3 and F-actin-binding filamin A or can interact with HCN2
    Neeliyath A Ramakrishnan
    Laboratory of Bio Otology, Department of Otolaryngology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
    J Biol Chem 287:37628-46. 2012
    ..is mediated by amino-terminal sequence specific to HCN1 and is not replicated by analogous specific peptides for HCN2 or HCN4 nor by amino-terminal sequence conserved across HCN isoforms utilized in channel formation...
  33. pmc Targeted deletion of Kcne2 impairs HCN channel function in mouse thalamocortical circuits
    Shui Wang Ying
    Department of Anesthesiology, Weill Cornell Medical College, New York, New York, United States of America
    PLoS ONE 7:e42756. 2012
    ..KCNE2 is a voltage-gated potassium channel ancillary subunit that also regulates heterologously expressed HCN channels; whether KCNE2 regulates neuronal HCN channel function is unknown...
  34. pmc Impaired dendritic expression and plasticity of h-channels in the fmr1(-/y) mouse model of fragile X syndrome
    Darrin H Brager
    Center for Learning and Memory, The University of Texas at Austin, Austin, TX 78712, USA
    Cell Rep 1:225-33. 2012
    ..Dendritic expression of the h-channel subunit HCN1, but not HCN2, was higher in the CA1 region of fmr1(-/y) mice...
  35. doi Ventricular HCN channels decrease the repolarization reserve in the hypertrophic heart
    Florian Hofmann
    Institut fur Experimentelle und Klinische Pharmakologie und Toxikologie, Friedrich Alexander Universitat Erlangen Nurnberg, Erlangen, Germany
    Cardiovasc Res 95:317-26. 2012
    ..However, the underlying mechanisms are not fully understood. Here, we analysed the role of the depolarizing current I(f) which has been hypothesized to contribute to arrhythmogenesis in the hypertrophied ventricle...
  36. doi HCN2 ion channels play a central role in inflammatory and neuropathic pain
    Edward C Emery
    Department of Pharmacology, University of Cambridge, Cambridge CB2 1PD, UK
    Science 333:1462-6. 2011
    ..We found that genetic deletion of HCN2 removed the cyclic adenosine monophosphate (cAMP)-sensitive component of I(h) and abolished action potential firing ..
  37. pmc HCN channelopathy in external globus pallidus neurons in models of Parkinson's disease
    C Savio Chan
    Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
    Nat Neurosci 14:85-92. 2011
    ..Viral delivery of HCN2 subunits restored pacemaking and reduced burst spiking in GPe neurons...
  38. pmc Deletion of the hyperpolarization-activated cyclic nucleotide-gated channel auxiliary subunit TRIP8b impairs hippocampal Ih localization and function and promotes antidepressant behavior in mice
    Alan S Lewis
    Davee Department of Neurology and Clinical Neurosciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA
    J Neurosci 31:7424-40. 2011
    ..We observed similar resistance to behavioral despair in distinct mutant mice lacking HCN1 or HCN2. These data demonstrate that interaction with the auxiliary subunit TRIP8b is a major mechanism underlying proper ..
  39. pmc State-dependent cAMP binding to functioning HCN channels studied by patch-clamp fluorometry
    Shengjun Wu
    Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
    Biophys J 100:1226-32. 2011
    ..Our results provide what we believe to be new insights into the cAMP-dependent gating in HCN channel and the interpretation of protein allostery for general ligand-gated channels and receptors...
  40. pmc Cytoplasmic cAMP-sensing domain of hyperpolarization-activated cation (HCN) channels uses two structurally distinct mechanisms to regulate voltage gating
    Nadine L Wicks
    Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, RI 02912, USA
    Proc Natl Acad Sci U S A 108:609-14. 2011
    ..Thus the liganded and the unliganded forms of the CSD respectively provide the structural determinants for open-state trapping and autoinhibition, such that two distinct mechanisms for cAMP regulation can operate in one receptor...
  41. pmc Hyperpolarization-activated cyclic nucleotide-gated channels in olfactory sensory neurons regulate axon extension and glomerular formation
    Arie S Mobley
    Department of Neurosurgery and Neurobiology, Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, Connecticut 06520 8082, USA
    J Neurosci 30:16498-508. 2010
    ..These data support the hypothesis that the outgrowth and coalescence of OSN axons is, at least in part, subject to activity-dependent mechanisms mediated via HCN channels...
  42. doi HCN2 channels in local inhibitory interneurons constrain LTP in the hippocampal direct perforant path
    Lucas Matt
    Institut fur Pharmakologie und Toxikologie der Technischen Universitat Munchen, Biedersteiner Straße 29, 80802 Munich, Germany
    Cell Mol Life Sci 68:125-37. 2011
    ..To evaluate the role of HCN2 for hippocampal synaptic plasticity, we recorded long-term potentiation (LTP) in the direct perforant path (PP) to ..
  43. pmc Functional expression of the hyperpolarization-activated, non-selective cation current I(f) in immortalized HL-1 cardiomyocytes
    Laura Sartiani
    Department of Preclinical and Clinical Pharmacology, University of Firenze, 50139 Florence, Italy
    J Physiol 545:81-92. 2002
    ..cyclic nucleotide-gated channels (HCN) expressed in HL-1 cells demonstrated major contributions of HCN1 and HCN2 channel isoforms to I(f) current...
  44. pmc HCN channels expressed in the inner ear are necessary for normal balance function
    Geoffrey C Horwitz
    Department of Neuroscience and Department of Otolaryngology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA
    J Neurosci 31:16814-25. 2011
    ..4 nS. I(h) was inhibited by ZD7288, cilobradine, and by adenoviral expression of a dominant-negative form of HCN2. To determine which HCN subunits carried I(h), we examined hair cells from mice deficient in Hcn1, 2, or both...
  45. ncbi A conserved domain in the NH2 terminus important for assembly and functional expression of pacemaker channels
    Neil Tran
    Ion Channel Laboratory, School of Kinesiology, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada
    J Biol Chem 277:43588-92. 2002
    ..Previously, we suggested that the NH(2) termini of the mouse HCN2 isoform were important for subunit co-assembly and functional channel expression...
  46. ncbi Separable gating mechanisms in a Mammalian pacemaker channel
    Vincenzo Macri
    Ion Channel Laboratory, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada
    J Biol Chem 277:35939-46. 2002
    ....
  47. ncbi Pacemaker channels produce an instantaneous current
    Catherine Proenza
    Ion Channel Laboratory, School of Kinesiology, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada
    J Biol Chem 277:5101-9. 2002
    ..Here, we report that the mouse HCN2 pacemaker channel isoform also produced a large instantaneous current (I(inst(HCN2))) in addition to the well ..
  48. pmc The S4-S5 linker couples voltage sensing and activation of pacemaker channels
    J Chen
    Department of Medicine, Division of Cardiology, Eccles Program in Human Molecular Biology and Genetics, University of Utah, Eccles Institute of Human Genetics, 15 N 2030 E, Room 4220, Salt Lake City, UT 84112, USA
    Proc Natl Acad Sci U S A 98:11277-82. 2001
    ..Here, we used alanine-scanning mutagenesis of the HCN2 S4-S5 linker to identify three residues, E324, Y331, and R339, that when mutated disrupted normal channel closing...
  49. ncbi A single histidine residue determines the pH sensitivity of the pacemaker channel HCN2
    X Zong
    Institut fur Pharmakologie und Toxikologie der Technischen Universitat Munchen, Biedersteiner Str 29, 80802 Munchen, Germany
    J Biol Chem 276:6313-9. 2001
    ..Here we demonstrate that HCN2, a member of the HCN channel family, is directly modulated by the intracellular pH in the physiological range...
  50. pmc NRSF regulates the fetal cardiac gene program and maintains normal cardiac structure and function
    Koichiro Kuwahara
    Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto 606 8507, Japan
    EMBO J 22:6310-21. 2003
    ..Our results indicate NRSF to be a key transcriptional regulator of the fetal cardiac gene program and suggest an important role for NRSF in maintaining normal cardiac structure and function...
  51. ncbi Evaluation of HCN2 abnormalities as a cause of juvenile audiogenic seizures in Black Swiss mice
    Minyoung Shin
    Davee Department of Neurology and Clinical Neurosciences, Northwestern University Medical School, 303 East Chicago Avenue, Ward Building 10 201, Chicago, IL 60611 3008, USA
    Brain Res 1083:14-20. 2006
    ..This region includes Hcn2, the gene encoding the hyperpolarization-activated cyclic nucleotide-gated channel subunit 2 (HCN2), an ion channel ..
  52. ncbi Membrane resting potential of thalamocortical relay neurons is shaped by the interaction among TASK3 and HCN2 channels
    Sven G Meuth
    Neurologische Klinik, Bayerische Julius Maximilians Universität, Wurzburg, Germany
    J Neurophysiol 96:1517-29. 2006
    ..Quantitative determination of mRNA expression levels and immunocytochemical staining demonstrated that TASK3 and HCN2 channels represent the dominant thalamic isoforms and are coexpressed in TC neurons...
  53. pmc Mode shifts in the voltage gating of the mouse and human HCN2 and HCN4 channels
    Fredrik Elinder
    Department of Biomedicine and Surgery, Division of Cell Biology, Linkopings Universitet, SE 581 85 Linkoping, Sweden
    J Physiol 575:417-31. 2006
    ..We found that HCN2 and HCN4 channels expressed in oocytes from the frog Xenopus laevis do not display the activation kinetic changes ..
  54. ncbi Single-channel properties support a potential contribution of hyperpolarization-activated cyclic nucleotide-gated channels and If to cardiac arrhythmias
    Guido Michels
    Department of Internal Medicine III, University of Cologne, Cologne, Germany
    Circulation 111:399-404. 2005
    ....
  55. ncbi Wild-type and mutant HCN channels in a tandem biological-electronic cardiac pacemaker
    Annalisa Bucchi
    Departments of Pharmacology, Center for Molecular Therapeutics, Columbia University, New York, NY 10032, USA
    Circulation 114:992-9. 2006
    ..We hypothesized that BPM engineered with the use of mE324A mutant murine HCN2 (mHCN2) genes would improve function over mHCN2 and that BPM/EPM tandems confer advantage over either approach alone...
  56. ncbi An arginine residue in the pore region is a key determinant of chloride dependence in cardiac pacemaker channels
    Christian Wahl-Schott
    Department Pharmazie Pharmakologie für Naturwissenschaften, Ludwig Maximilians Universitat Munchen, Butenandtstr 7 13, 81377 Munchen, Germany
    J Biol Chem 280:13694-700. 2005
    ..Currents carried by the two cardiac HCN channel isoforms (HCN2 and HCN4) showed the same strong Cl- dependence as the sinoatrial I(f) and decreased to about 10% in the absence of ..
  57. pmc Voltage sensor movement and cAMP binding allosterically regulate an inherently voltage-independent closed-open transition in HCN channels
    Shan Chen
    Center for Neurobiology and Behavior, Columbia University, New York, NY 10032, USA
    J Gen Physiol 129:175-88. 2007
    ..Here we have addressed the mechanism of this dual regulation for HCN2 channels, which activate with slow kinetics that are strongly accelerated by cAMP, and HCN1 channels, which ..
  58. ncbi Arrhythmia induced by spatiotemporal overexpression of calreticulin in the heart
    Kiyoko Hattori
    Department of Pediatrics, Graduate School of Medical Science, Kumamoto University, Japan
    Mol Genet Metab 91:285-93. 2007
    ..Our findings support calreticulin being critical for normal heart function and structure. These mice are a useful model for the study of endoplasmic reticulum proteins, such as calreticulin, in various tissues...
  59. ncbi Interaction of the pacemaker channel HCN1 with filamin A
    Biagio Gravante
    Department of Biomolecular Sciences and Biotechnology, Laboratory of Molecular Physiology and Neurobiology, University of Milano, Via Celoria 26, 20133, Italy
    J Biol Chem 279:43847-53. 2004
    ..here we showed that filamin A interacts with HCN1, an HCN isoform widely expressed in the brain, but not with HCN2 or HCN4...
  60. pmc Thyroid hormone receptor alpha is a molecular switch of cardiac function between fetal and postnatal life
    Wilfried Mai
    Animage Rhône Alpes Genopole, Unite Mixte de Recherche, Centre National de la Recherche Scientifique 5515, 59 Boulevard Pinel, 69003 Lyon, France
    Proc Natl Acad Sci U S A 101:10332-7. 2004
    ..These data describe a physiological situation under which conversion of TRalpha from apo-receptors into holo-receptors, upon changes in T3 availability, plays a determinant role in a developmental process...
  61. ncbi 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
    ..the HCN channel blocker, ZD7288 [4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride] on HCN2 channels that were heterologously expressed in Xenopus oocytes...
  62. pmc cAMP Modulation of the cytoplasmic domain in the HCN2 channel investigated by molecular simulations
    Marco Berrera
    Scuola Internazionale Superiore di Studi Avanzati and Istituto Nazionale per la Fisica della Materia, Democritos Modeling Center for Research in Atomic Simulation, Trieste, Italy
    Biophys J 90:3428-33. 2006
    ..nucleotide binding domain (CNBD) in the presence and absence of cAMP, based on the available crystal structure of HCN2 from mouse...
  63. doi Direct evidence for calcium conductance of hyperpolarization-activated cyclic nucleotide-gated channels and human native If at physiological calcium concentrations
    Guido Michels
    Department of Internal Medicine III, University of Cologne, Kerpener Str 62, 50937 Cologne, Germany
    Cardiovasc Res 78:466-75. 2008
    ..Recently, Ca(2+) influx through HCN channels has indirectly been postulated. However, direct functional evidence of Ca(2+) permeation through I(f)/I(HCN) is still lacking...
  64. pmc Intracellular Mg2+ is a voltage-dependent pore blocker of HCN channels
    Sriharsha Vemana
    Neurological Sciences Institute, Oregon Health and Science Univ, 505 NW 185th Ave, Beaverton, OR 97006, USA
    Am J Physiol Cell Physiol 295:C557-65. 2008
    ..53 mM in HCN2 channels and 0.82 mM in HCN1 channels at +50 mV...
  65. pmc Novel mechanism for suppression of hyperpolarization-activated cyclic nucleotide-gated pacemaker channels by receptor-like tyrosine phosphatase-alpha
    Jianying Huang
    Center for Interdisciplinary Research in Cardiovascular Sciences, Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, West Virginia 26506, USA
    J Biol Chem 283:29912-9. 2008
    ..found that the receptor-like protein-tyrosine phosphatase-alpha (RPTPalpha) significantly inhibited or eliminated HCN2 channel expression in HEK293 cells...
  66. pmc Molecular basis of the effect of potassium on heterologously expressed pacemaker (HCN) channels
    Ezana M Azene
    Institute of Molecular Cardiobiology, The Johns Hopkins University School of Medicine, 720 Rutland Avenue Ross 844, Baltimore, MD 21205, USA
    J Physiol 547:349-56. 2003
    ..Here we examined the effects of external permeant (K+, Na+ and Li+) and non-permeant (NMG+) ions on HCN1 and HCN2 gating...
  67. pmc In vitro characterization of HCN channel kinetics and frequency dependence in myocytes predicts biological pacemaker functionality
    Xin Zhao
    Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, NY, USA
    J Physiol 587:1513-25. 2009
    ..Previous experiments creating HCN-based biological pacemakers in vivo found that an engineered HCN2/HCN1 chimeric channel (HCN212) resulted in significantly faster rates than HCN2, interrupted by 1-5 s pauses...
  68. pmc Alanine scanning of the S6 segment reveals a unique and cAMP-sensitive association between the pore and voltage-dependent opening in HCN channels
    Vincenzo Macri
    Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    J Biol Chem 284:15659-67. 2009
    ..Accordingly, we performed a 22-residue alanine/valine scan of the distal pore of the HCN2 isoform and show that the effects of mutations on channel opening and on the steepness of the response of the ..
  69. pmc Transcription profiling of HCN-channel isotypes throughout mouse cardiac development
    Patrick A Schweizer
    Universitatsklinikum Heidelberg, Innere Medizin III, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany
    Basic Res Cardiol 104:621-9. 2009
    ..After birth, however, HCN isotype transcription changed remarkably, showing increased levels of HCN1, HCN2 and HCN4 in the atrium and of HCN2 and HCN4 in the ventricle...
  70. pmc Voltage-dependent opening of HCN channels: Facilitation or inhibition by the phytoestrogen, genistein, is determined by the activation status of the cyclic nucleotide gating ring
    Anjali O Rozario
    Department of Anesthesiology, Columbia University, New York, NY 10032, USA
    Biochim Biophys Acta 1788:1939-49. 2009
    ..8 mV + or - 0.9 versus +2.2 mV + or - 0.6) and hyperpolarizes gating of HCN2 (-4.8 mV + or - 1.0) but depolarizes gating of HCN2-R591E (+13.2 mV + or - 2.1)...
  71. pmc Proteolytic processing of HCN2 and co-assembly with HCN4 in the generation of cardiac pacemaker channels
    Bin Ye
    Department of Medicine and Public Health, Division of Cardiovascular Medicine, University of Wisconsin Madison, Madison, Wisconsin 53706, USA
    J Biol Chem 284:25553-9. 2009
    ..Although previous studies have demonstrated myocardial expression of both the HCN2 and HCN4 subunits, the specific roles of these subunits in the generation of functional myocardial I(f) channels ..
  72. doi Evolutionary emergence of N-glycosylation as a variable promoter of HCN channel surface expression
    Andrew P Hegle
    Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, Canada
    Am J Physiol Cell Physiol 298:C1066-76. 2010
    ..With the mouse HCN2 isoform as a prototype, HCN channels have further been suggested to require N-glycosylation for function, a ..
  73. pmc Hyperpolarization-activated and cyclic nucleotide-gated channels are differentially expressed in juxtaglomerular cells in the olfactory bulb of mice
    Hans Ulrich Fried
    Abteilung Molekulare Neurosensorik, Center of Advanced European Studies and Research, Bonn, Germany
    Cell Tissue Res 339:463-79. 2010
    ..The staining patterns are consistent with the possibility that both homomeric and heteromeric HCN channels are involved in oscillations of the membrane potential of juxtaglomerular cells...