HCN4

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Hyperpolarization activated cyclic nucleotide gated potassium channel 4
Protein HCN4 PDB 1q3e.png
PDB rendering based on 1q3e.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols HCN4 ; SSS2
External IDs OMIM605206 MGI1298209 HomoloGene3997 IUPHAR: 403 ChEMBL: 1250417 GeneCards: HCN4 Gene
RNA expression pattern
PBB GE HCN4 206946 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 10021 330953
Ensembl ENSG00000138622 ENSMUSG00000032338
UniProt Q9Y3Q4 O70507
RefSeq (mRNA) NM_005477 NM_001081192
RefSeq (protein) NP_005468 NP_001074661
Location (UCSC) Chr 15:
73.32 – 73.37 Mb
Chr 9:
58.82 – 58.86 Mb
PubMed search [1] [2]

Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 is a protein that in humans is encoded by the HCN4 gene.[1][2][3][4]

There are four HCN channels. HCN4 is prominently expressed in the pace maker region of the mammalian heart.[5] Some humans with bradycardia and Sick sinus syndrome have been shown to have mutations in their HCN4 gene.[6][7] The role of HCN channels in autonomic control of heart rate is currently a matter of ongoing investigation.[8][9][10][11]

Interactions[edit]

HCN4 has been shown to interact with HCN2.[12]

See also[edit]

References[edit]

  1. ^ Ludwig A, Zong X, Stieber J, Hullin R, Hofmann F, Biel M (May 1999). "Two pacemaker channels from human heart with profoundly different activation kinetics". The EMBO Journal 18 (9): 2323–9. doi:10.1093/emboj/18.9.2323. PMC 1171315. PMID 10228147. 
  2. ^ Seifert R, Scholten A, Gauss R, Mincheva A, Lichter P, Kaupp UB (Aug 1999). "Molecular characterization of a slowly gating human hyperpolarization-activated channel predominantly expressed in thalamus, heart, and testis". Proceedings of the National Academy of Sciences of the United States of America 96 (16): 9391–6. doi:10.1073/pnas.96.16.9391. PMC 17793. PMID 10430953. 
  3. ^ Hofmann F, Biel M, Kaupp UB (Dec 2005). "International Union of Pharmacology. LI. Nomenclature and structure-function relationships of cyclic nucleotide-regulated channels". Pharmacological Reviews 57 (4): 455–62. doi:10.1124/pr.57.4.8. PMID 16382102. 
  4. ^ "Entrez Gene: HCN4 hyperpolarization activated cyclic nucleotide-gated potassium channel 4". 
  5. ^ Baruscotti M, Bucchi A, Viscomi C, Mandelli G, Consalez G, Gnecchi-Rusconi T, Montano N, Casali KR, Micheloni S, Barbuti A, DiFrancesco D (Jan 2011). "Deep bradycardia and heart block caused by inducible cardiac-specific knockout of the pacemaker channel gene Hcn4". Proceedings of the National Academy of Sciences of the United States of America 108 (4): 1705–10. doi:10.1073/pnas.1010122108. PMC 3029742. PMID 21220308. 
  6. ^ Schulze-Bahr E, Neu A, Friederich P, Kaupp UB, Breithardt G, Pongs O, Isbrandt D (May 2003). "Pacemaker channel dysfunction in a patient with sinus node disease". The Journal of Clinical Investigation 111 (10): 1537–45. doi:10.1172/JCI16387. PMC 155041. PMID 12750403. 
  7. ^ Laish-Farkash A, Glikson M, Brass D, Marek-Yagel D, Pras E, Dascal N, Antzelevitch C, Nof E, Reznik H, Eldar M, Luria D (Dec 2010). "A novel mutation in the HCN4 gene causes symptomatic sinus bradycardia in Moroccan Jews". Journal of Cardiovascular Electrophysiology 21 (12): 1365–72. doi:10.1111/j.1540-8167.2010.01844.x. PMC 3005590. PMID 20662977. 
  8. ^ Larsson HP (Sep 2010). "How is the heart rate regulated in the sinoatrial node? Another piece to the puzzle". The Journal of General Physiology 136 (3): 237–41. doi:10.1085/jgp.201010506. PMC 2931147. PMID 20713549. 
  9. ^ Schweizer PA, Duhme N, Thomas D, Becker R, Zehelein J, Draguhn A, Bruehl C, Katus HA, Koenen M (Oct 2010). "cAMP sensitivity of HCN pacemaker channels determines basal heart rate but is not critical for autonomic rate control". Circulation. Arrhythmia and Electrophysiology 3 (5): 542–52. doi:10.1161/CIRCEP.110.949768. PMID 20693575. 
  10. ^ Liao Z, Lockhead D, Larson ED, Proenza C (Sep 2010). "Phosphorylation and modulation of hyperpolarization-activated HCN4 channels by protein kinase A in the mouse sinoatrial node". The Journal of General Physiology 136 (3): 247–58. doi:10.1085/jgp.201010488. PMC 2931151. PMID 20713547. 
  11. ^ Nof E, Antzelevitch C, Glikson M (Jan 2010). "The Contribution of HCN4 to normal sinus node function in humans and animal models". Pacing and Clinical Electrophysiology 33 (1): 100–6. doi:10.1111/j.1540-8159.2009.02563.x. PMC 2865562. PMID 19796353. 
  12. ^ Much B, Wahl-Schott C, Zong X, Schneider A, Baumann L, Moosmang S, Ludwig A, Biel M (Oct 2003). "Role of subunit heteromerization and N-linked glycosylation in the formation of functional hyperpolarization-activated cyclic nucleotide-gated channels". The Journal of Biological Chemistry 278 (44): 43781–6. doi:10.1074/jbc.M306958200. PMID 12928435. 

Further reading[edit]

  • Qu J, Altomare C, Bucchi A, DiFrancesco D, Robinson RB (Aug 2002). "Functional comparison of HCN isoforms expressed in ventricular and HEK 293 cells". Pflügers Archiv 444 (5): 597–601. doi:10.1007/s00424-002-0860-7. PMID 12194012. 
  • Schulze-Bahr E, Neu A, Friederich P, Kaupp UB, Breithardt G, Pongs O, Isbrandt D (May 2003). "Pacemaker channel dysfunction in a patient with sinus node disease". The Journal of Clinical Investigation 111 (10): 1537–45. doi:10.1172/JCI16387. PMC 155041. PMID 12750403. 
  • Stieber J, Thomer A, Much B, Schneider A, Biel M, Hofmann F (Sep 2003). "Molecular basis for the different activation kinetics of the pacemaker channels HCN2 and HCN4". The Journal of Biological Chemistry 278 (36): 33672–80. doi:10.1074/jbc.M305318200. PMID 12813043. 
  • Decher N, Bundis F, Vajna R, Steinmeyer K (Sep 2003). "KCNE2 modulates current amplitudes and activation kinetics of HCN4: influence of KCNE family members on HCN4 currents". Pflügers Archiv 446 (6): 633–40. doi:10.1007/s00424-003-1127-7. PMID 12856183. 
  • Much B, Wahl-Schott C, Zong X, Schneider A, Baumann L, Moosmang S, Ludwig A, Biel M (Oct 2003). "Role of subunit heteromerization and N-linked glycosylation in the formation of functional hyperpolarization-activated cyclic nucleotide-gated channels". The Journal of Biological Chemistry 278 (44): 43781–6. doi:10.1074/jbc.M306958200. PMID 12928435. 
  • Ueda K, Nakamura K, Hayashi T, Inagaki N, Takahashi M, Arimura T, Morita H, Higashiuesato Y, Hirano Y, Yasunami M, Takishita S, Yamashina A, Ohe T, Sunamori M, Hiraoka M, Kimura A (Jun 2004). "Functional characterization of a trafficking-defective HCN4 mutation, D553N, associated with cardiac arrhythmia". The Journal of Biological Chemistry 279 (26): 27194–8. doi:10.1074/jbc.M311953200. PMID 15123648. 
  • Michels G, Er F, Khan I, Südkamp M, Herzig S, Hoppe UC (Feb 2005). "Single-channel properties support a potential contribution of hyperpolarization-activated cyclic nucleotide-gated channels and If to cardiac arrhythmias". Circulation 111 (4): 399–404. doi:10.1161/01.CIR.0000153799.65783.3A. PMID 15687126. 
  • Milanesi R, Baruscotti M, Gnecchi-Ruscone T, DiFrancesco D (Jan 2006). "Familial sinus bradycardia associated with a mutation in the cardiac pacemaker channel". The New England Journal of Medicine 354 (2): 151–7. doi:10.1056/NEJMoa052475. PMID 16407510. 
  • Elinder F, Männikkö R, Pandey S, Larsson HP (Sep 2006). "Mode shifts in the voltage gating of the mouse and human HCN2 and HCN4 channels". The Journal of Physiology 575 (Pt 2): 417–31. doi:10.1113/jphysiol.2006.110437. PMC 1819464. PMID 16777944. 
  • Nof E, Luria D, Brass D, Marek D, Lahat H, Reznik-Wolf H, Pras E, Dascal N, Eldar M, Glikson M (Jul 2007). "Point mutation in the HCN4 cardiac ion channel pore affecting synthesis, trafficking, and functional expression is associated with familial asymptomatic sinus bradycardia". Circulation 116 (5): 463–70. doi:10.1161/CIRCULATIONAHA.107.706887. PMID 17646576. 

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.