HCN4

{{short description|Protein-coding gene in the species Homo sapiens}}

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{{Infobox gene}}

Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 is a protein that in humans is encoded by the HCN4 gene.{{cite journal | vauthors = Ludwig A, Zong X, Stieber J, Hullin R, Hofmann F, Biel M | title = Two pacemaker channels from human heart with profoundly different activation kinetics | journal = The EMBO Journal | volume = 18 | issue = 9 | pages = 2323–2329 | date = May 1999 | pmid = 10228147 | pmc = 1171315 | doi = 10.1093/emboj/18.9.2323 }}{{cite journal | vauthors = Seifert R, Scholten A, Gauss R, Mincheva A, Lichter P, Kaupp UB | title = Molecular characterization of a slowly gating human hyperpolarization-activated channel predominantly expressed in thalamus, heart, and testis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 16 | pages = 9391–9396 | date = Aug 1999 | pmid = 10430953 | pmc = 17793 | doi = 10.1073/pnas.96.16.9391 | bibcode = 1999PNAS...96.9391S | doi-access = free }}{{cite journal | vauthors = Hofmann F, Biel M, Kaupp UB | title = International Union of Pharmacology. LI. Nomenclature and structure-function relationships of cyclic nucleotide-regulated channels | journal = Pharmacological Reviews | volume = 57 | issue = 4 | pages = 455–462 | date = Dec 2005 | pmid = 16382102 | doi = 10.1124/pr.57.4.8 | s2cid = 45853869 }}{{cite web | title = Entrez Gene: HCN4 hyperpolarization activated cyclic nucleotide-gated potassium channel 4 | url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10021 }}

There are four HCN channels. HCN4 is prominently expressed in the pace maker region of the mammalian heart.{{cite journal | vauthors = Baruscotti M, Bucchi A, Viscomi C, Mandelli G, Consalez G, Gnecchi-Rusconi T, Montano N, Casali KR, Micheloni S, Barbuti A, DiFrancesco D | title = Deep bradycardia and heart block caused by inducible cardiac-specific knockout of the pacemaker channel gene Hcn4 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 4 | pages = 1705–1710 | date = Jan 2011 | pmid = 21220308 | pmc = 3029742 | doi = 10.1073/pnas.1010122108 | bibcode = 2011PNAS..108.1705B | doi-access = free }} Some humans with bradycardia and Sick sinus syndrome have been shown to have mutations in their HCN4 gene.{{cite journal | vauthors = Jou CJ, Arrington CB, Barnett S, Shen J, Cho S, Sheng X, McCullagh PC, Bowles NE, Pribble CM, Saarel EV, Pilcher TA, Etheridge SP, Tristani-Firouzi M | title = A Functional Assay for Sick Sinus Syndrome Genetic Variants | journal = Cellular Physiology and Biochemistry | volume = 42 | issue = 5 | pages = 2021–2029 | date = 2017 | pmid = 28803248 | doi = 10.1159/000479897 | url = https://www.karger.com/Article/FullText/479897 | language = english | issn = 1015-8987 | doi-access = free }}{{cite journal | vauthors = Schulze-Bahr E, Neu A, Friederich P, Kaupp UB, Breithardt G, Pongs O, Isbrandt D | title = Pacemaker channel dysfunction in a patient with sinus node disease | journal = The Journal of Clinical Investigation | volume = 111 | issue = 10 | pages = 1537–1545 | date = May 2003 | pmid = 12750403 | pmc = 155041 | doi = 10.1172/JCI16387 }}{{cite journal | vauthors = Laish-Farkash A, Glikson M, Brass D, Marek-Yagel D, Pras E, Dascal N, Antzelevitch C, Nof E, Reznik H, Eldar M, Luria D | title = A novel mutation in the HCN4 gene causes symptomatic sinus bradycardia in Moroccan Jews | journal = Journal of Cardiovascular Electrophysiology | volume = 21 | issue = 12 | pages = 1365–1372 | date = Dec 2010 | pmid = 20662977 | pmc = 3005590 | doi = 10.1111/j.1540-8167.2010.01844.x }} The role of HCN channels in autonomic control of heart rate is currently a matter of ongoing investigation.{{cite journal | vauthors = Larsson HP | title = How is the heart rate regulated in the sinoatrial node? Another piece to the puzzle | journal = The Journal of General Physiology | volume = 136 | issue = 3 | pages = 237–241 | date = Sep 2010 | pmid = 20713549 | pmc = 2931147 | doi = 10.1085/jgp.201010506 }}{{cite journal | vauthors = Schweizer PA, Duhme N, Thomas D, Becker R, Zehelein J, Draguhn A, Bruehl C, Katus HA, Koenen M | title = cAMP sensitivity of HCN pacemaker channels determines basal heart rate but is not critical for autonomic rate control | journal = Circulation. Arrhythmia and Electrophysiology | volume = 3 | issue = 5 | pages = 542–552 | date = Oct 2010 | pmid = 20693575 | doi = 10.1161/CIRCEP.110.949768 | doi-access = free | hdl = 11858/00-001M-0000-002C-5DAB-C | hdl-access = free }}{{cite journal | vauthors = Liao Z, Lockhead D, Larson ED, Proenza C | title = Phosphorylation and modulation of hyperpolarization-activated HCN4 channels by protein kinase A in the mouse sinoatrial node | journal = The Journal of General Physiology | volume = 136 | issue = 3 | pages = 247–258 | date = Sep 2010 | pmid = 20713547 | pmc = 2931151 | doi = 10.1085/jgp.201010488 }}{{cite journal | vauthors = Nof E, Antzelevitch C, Glikson M | title = The Contribution of HCN4 to normal sinus node function in humans and animal models | journal = Pacing and Clinical Electrophysiology | volume = 33 | issue = 1 | pages = 100–106 | date = Jan 2010 | pmid = 19796353 | pmc = 2865562 | doi = 10.1111/j.1540-8159.2009.02563.x }}