From Wikipedia, the free encyclopedia
Protein-coding gene in the species Homo sapiens
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 is a
protein that in humans is encoded by the HCN4
gene .
[5]
[6]
[7]
[8]
There are four
HCN channels . HCN4 is prominently expressed in the
pace maker region of the mammalian
heart .
[9] Some humans with
bradycardia and
Sick sinus syndrome have been shown to have mutations in their HCN4 gene.
[10]
[11]
[12] The role of HCN channels in
autonomic control of heart rate is currently a matter of ongoing investigation.
[13]
[14]
[15]
[16]
Interactions
HCN4 has been shown to
interact with
HCN2 .
[17]
See also
References
^
a
b
c
GRCh38: Ensembl release 89: ENSG00000138622 –
Ensembl , May 2017
^
a
b
c
GRCm38: Ensembl release 89: ENSMUSG00000032338 –
Ensembl , May 2017
^
"Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
"Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^ 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 .
^ 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.
Bibcode :
1999PNAS...96.9391S .
doi :
10.1073/pnas.96.16.9391 .
PMC
17793 .
PMID
10430953 .
^ 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 .
S2CID
45853869 .
^
"Entrez Gene: HCN4 hyperpolarization activated cyclic nucleotide-gated potassium channel 4" .
^ 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.
Bibcode :
2011PNAS..108.1705B .
doi :
10.1073/pnas.1010122108 .
PMC
3029742 .
PMID
21220308 .
^ Jou, Chuanchau J.; Arrington, Cammon B.; Barnett, Spencer M; Shen, Jiaxiang; Cho, Scott; Sheng, Xiaoming; McCullagh, Patrick C.; Bowles, Neil E.; Pribble, Chase M.; Saarel, Elizabeth V.; Pilcher, Thomas A.; Etheridge, Susan P.; Tristani-Firouzi, Martin (2017).
"A Functional Assay for Sick Sinus Syndrome Genetic Variants" . Cellular Physiology and Biochemistry . 42 (5): 2021–2029.
doi :
10.1159/000479897 .
ISSN
1015-8987 .
PMID
28803248 .
^ 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 .
^ 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 .
^
^ 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 .
hdl :
11858/00-001M-0000-002C-5DAB-C .
PMID
20693575 .
^ 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 .
^ 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 .
^ 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
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 .
S2CID
508732 .
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 .
S2CID
21513896 .
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
This article incorporates text from the
United States National Library of Medicine , which is in the
public domain .
PDB gallery
1q3e : HCN2J 443-645 in the presence of cGMP
1q43 : HCN2I 443-640 in the presence of cAMP, selenomethionine derivative
1q5o : HCN2J 443-645 in the presence of cAMP, selenomethionine derivative