Biology:HCN4
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Short description: Protein-coding gene in the species Homo sapiens
 Generic protein structure example |
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][8] The role of HCN channels in autonomic control of heart rate is currently a matter of ongoing investigation.[9][10][11][12]
Interactions
HCN4 has been shown to interact with HCN2.[13]
See also
- Cyclic nucleotide-gated ion channel
- Funny current
References
- ↑ "Two pacemaker channels from human heart with profoundly different activation kinetics". The EMBO Journal 18 (9): 2323–9. May 1999. doi:10.1093/emboj/18.9.2323. PMID 10228147.
- ↑ "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. Aug 1999. doi:10.1073/pnas.96.16.9391. PMID 10430953. Bibcode: 1999PNAS...96.9391S.
- ↑ "International Union of Pharmacology. LI. Nomenclature and structure-function relationships of cyclic nucleotide-regulated channels". Pharmacological Reviews 57 (4): 455–62. Dec 2005. doi:10.1124/pr.57.4.8. PMID 16382102.
- ↑ "Entrez Gene: HCN4 hyperpolarization activated cyclic nucleotide-gated potassium channel 4". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10021.
- ↑ "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. Jan 2011. doi:10.1073/pnas.1010122108. PMID 21220308. Bibcode: 2011PNAS..108.1705B.
- ↑ Jou, Chuanchau J.; Arrington, Cammon B.; Barnett, Spencer M; Shen, Jiaxiang; Cho, Scott; Sheng, Xiaoming; McCullagh, Patrick C.; Bowles, Neil E. et al. (2017). "A Functional Assay for Sick Sinus Syndrome Genetic Variants" (in english). Cellular Physiology and Biochemistry 42 (5): 2021–2029. doi:10.1159/000479897. ISSN 1015-8987. PMID 28803248. https://www.karger.com/Article/FullText/479897.
- ↑ "Pacemaker channel dysfunction in a patient with sinus node disease". The Journal of Clinical Investigation 111 (10): 1537–45. May 2003. doi:10.1172/JCI16387. PMID 12750403.
- ↑ "A novel mutation in the HCN4 gene causes symptomatic sinus bradycardia in Moroccan Jews". Journal of Cardiovascular Electrophysiology 21 (12): 1365–72. Dec 2010. doi:10.1111/j.1540-8167.2010.01844.x. PMID 20662977.
- ↑ "How is the heart rate regulated in the sinoatrial node? Another piece to the puzzle". The Journal of General Physiology 136 (3): 237–41. Sep 2010. doi:10.1085/jgp.201010506. PMID 20713549.
- ↑ "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. Oct 2010. doi:10.1161/CIRCEP.110.949768. PMID 20693575.
- ↑ "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. Sep 2010. doi:10.1085/jgp.201010488. PMID 20713547.
- ↑ "The Contribution of HCN4 to normal sinus node function in humans and animal models". Pacing and Clinical Electrophysiology 33 (1): 100–6. Jan 2010. doi:10.1111/j.1540-8159.2009.02563.x. PMID 19796353.
- ↑ "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. Oct 2003. doi:10.1074/jbc.M306958200. PMID 12928435.
Further reading
- "Functional comparison of HCN isoforms expressed in ventricular and HEK 293 cells". Pflügers Archiv 444 (5): 597–601. Aug 2002. doi:10.1007/s00424-002-0860-7. PMID 12194012.
- "Pacemaker channel dysfunction in a patient with sinus node disease". The Journal of Clinical Investigation 111 (10): 1537–45. May 2003. doi:10.1172/JCI16387. PMID 12750403.
- "Molecular basis for the different activation kinetics of the pacemaker channels HCN2 and HCN4". The Journal of Biological Chemistry 278 (36): 33672–80. Sep 2003. doi:10.1074/jbc.M305318200. PMID 12813043.
- "KCNE2 modulates current amplitudes and activation kinetics of HCN4: influence of KCNE family members on HCN4 currents". Pflügers Archiv 446 (6): 633–40. Sep 2003. doi:10.1007/s00424-003-1127-7. PMID 12856183.
- "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. Oct 2003. doi:10.1074/jbc.M306958200. PMID 12928435.
- "Functional characterization of a trafficking-defective HCN4 mutation, D553N, associated with cardiac arrhythmia". The Journal of Biological Chemistry 279 (26): 27194–8. Jun 2004. doi:10.1074/jbc.M311953200. PMID 15123648.
- "Single-channel properties support a potential contribution of hyperpolarization-activated cyclic nucleotide-gated channels and If to cardiac arrhythmias". Circulation 111 (4): 399–404. Feb 2005. doi:10.1161/01.CIR.0000153799.65783.3A. PMID 15687126.
- "Familial sinus bradycardia associated with a mutation in the cardiac pacemaker channel". The New England Journal of Medicine 354 (2): 151–7. Jan 2006. doi:10.1056/NEJMoa052475. PMID 16407510.
- "Mode shifts in the voltage gating of the mouse and human HCN2 and HCN4 channels". The Journal of Physiology 575 (Pt 2): 417–31. Sep 2006. doi:10.1113/jphysiol.2006.110437. PMID 16777944.
- "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. Jul 2007. doi:10.1161/CIRCULATIONAHA.107.706887. PMID 17646576.
External links
- GeneReviews/NIH/NCBI/UW entry on Brugada syndrome
- HCN4+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
- HCN4 human gene location in the UCSC Genome Browser.
- HCN4 human gene details in the UCSC Genome Browser.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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