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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
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
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:
73.61 – 73.66 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]


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

See also[edit]


  1. ^ Ludwig A, Zong X, Stieber J, Hullin R, Hofmann F, Biel M (Jun 1999). "Two pacemaker channels from human heart with profoundly different activation kinetics". EMBO J 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 (Sep 1999). "Molecular characterization of a slowly gating human hyperpolarization-activated channel predominantly expressed in thalamus, heart, and testis". Proc Natl Acad Sci U S A 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". Pharmacol Rev 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, K. R.; Micheloni, S.; Barbuti, A.; Difrancesco, D. (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 108 (4): 1705–1710. doi:10.1073/pnas.1010122108. PMC 3029742. PMID 21220308.  edit
  6. ^ Schulze-Bahr, E.; Neu, A.; Friederich, P.; Kaupp, U. B.; Breithardt, G. N.; Pongs, O.; Isbrandt, D. (2003). "Pacemaker channel dysfunction in a patient with sinus node disease". Journal of Clinical Investigation 111 (10): 1537–1545. doi:10.1172/JCI16387. PMC 155041. PMID 12750403.  edit
  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. (2010). "A Novel Mutation in the Hcn4 Gene Causes Symptomatic Sinus Bradycardia in Moroccan Jews". Journal of Cardiovascular Electrophysiology 21 (12): 1365–1372. doi:10.1111/j.1540-8167.2010.01844.x. PMC 3005590. PMID 20662977.  edit
  8. ^ Larsson, H. P. (2010). "How is the heart rate regulated in the sinoatrial node? Another piece to the puzzle". The Journal of General Physiology 136 (3): 237–241. doi:10.1085/jgp.201010506. PMC 2931147. PMID 20713549.  edit
  9. ^ Schweizer, P. A.; Duhme, N.; Thomas, D.; Becker, R.; Zehelein, J.; Draguhn, A.; Bruehl, C.; Katus, H. A.; Koenen, M. (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): 542–552. doi:10.1161/CIRCEP.110.949768. PMID 20693575.  edit
  10. ^ Liao, Z.; Lockhead, D.; Larson, E. D.; Proenza, C. (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): 247–258. doi:10.1085/jgp.201010488. PMC 2931151. PMID 20713547.  edit
  11. ^ Nof, E.; Antzelevitch, C.; Glikson, M. (2010). "The Contribution of HCN4 to Normal Sinus Node Function in Humans and Animal Models". Pacing and Clinical Electrophysiology 33 (1): 100–106. doi:10.1111/j.1540-8159.2009.02563.x. PMC 2865562. PMID 19796353.  edit
  12. ^ Much, Barbara; Wahl-Schott Christian, Zong Xiangang, Schneider Angela, Baumann Ludwig, Moosmang Sven, Ludwig Andreas, Biel Martin (Oct 2003). "Role of subunit heteromerization and N-linked glycosylation in the formation of functional hyperpolarization-activated cyclic nucleotide-gated channels". J. Biol. Chem. (United States) 278 (44): 43781–6. doi:10.1074/jbc.M306958200. ISSN 0021-9258. PMID 12928435. 

Further reading[edit]

External links[edit]

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