HCN1

Hyperpolarization-activated cation channels of the HCN gene family, such as HCN1, contribute to spontaneous rhythmic activity in both heart and brain.

HCN1 channel expression is found in the sinoatrial node,{{cite journal | vauthors = Marionneau C, Couette B, Liu J, Li H, Mangoni ME, Nargeot J, Lei M, Escande D, Demolombe S | display-authors = 6 | title = Specific pattern of ionic channel gene expression associated with pacemaker activity in the mouse heart | journal = The Journal of Physiology | volume = 562 | issue = Pt 1 | pages = 223–234 | date = January 2005 | pmid = 15498808 | pmc = 1665484 | doi = 10.1113/jphysiol.2004.074047 }}{{cite journal | vauthors = Shi W, Wymore R, Yu H, Wu J, Wymore RT, Pan Z, Robinson RB, Dixon JE, McKinnon D, Cohen IS | display-authors = 6 | title = Distribution and prevalence of hyperpolarization-activated cation channel (HCN) mRNA expression in cardiac tissues | journal = Circulation Research | volume = 85 | issue = 1 | pages = e1–e6 | date = July 1999 | pmid = 10400919 | doi = 10.1161/01.RES.85.1.e1 | doi-access = free }} the neocortex, hippocampus, cerebellar cortex, dorsal root ganglion, trigeminal ganglion and brainstem.{{cite journal | vauthors = Lörincz A, Notomi T, Tamás G, Shigemoto R, Nusser Z | title = Polarized and compartment-dependent distribution of HCN1 in pyramidal cell dendrites | journal = Nature Neuroscience | volume = 5 | issue = 11 | pages = 1185–1193 | date = November 2002 | pmid = 12389030 | doi = 10.1038/nn962 | s2cid = 18132966 }}{{cite journal | vauthors = Milligan CJ, Edwards IJ, Deuchars J | title = HCN1 ion channel immunoreactivity in spinal cord and medulla oblongata | journal = Brain Research | volume = 1081 | issue = 1 | pages = 79–91 | date = April 2006 | pmid = 16503331 | doi = 10.1016/j.brainres.2006.01.019 | s2cid = 30929772 }}{{cite journal | vauthors = Moosmang S, Biel M, Hofmann F, Ludwig A | title = Differential distribution of four hyperpolarization-activated cation channels in mouse brain | journal = Biological Chemistry | volume = 380 | issue = 7–8 | pages = 975–980 | year = 1999 | pmid = 10494850 | doi = 10.1515/BC.1999.121 | s2cid = 22722872 }}{{cite journal | vauthors = Wells JE, Rowland KC, Proctor EK | title = Hyperpolarization-activated channels in trigeminal ganglia innervating healthy and pulp-exposed teeth | journal = International Endodontic Journal | volume = 40 | issue = 9 | pages = 715–721 | date = September 2007 | pmid = 17645513 | doi = 10.1111/j.1365-2591.2007.01297.x }}{{cite journal | vauthors = Santoro B, Grant SG, Bartsch D, Kandel ER | title = Interactive cloning with the SH3 domain of N-src identifies a new brain specific ion channel protein, with homology to eag and cyclic nucleotide-gated channels | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 26 | pages = 14815–14820 | date = December 1997 | pmid = 9405696 | pmc = 25120 | doi = 10.1073/pnas.94.26.14815 | doi-access = free | bibcode = 1997PNAS...9414815S }}

• Ketamine is an inhibitor of HCN1 in addition to its other targets.{{cite journal | vauthors = Chen X, Shu S, Bayliss DA | title = HCN1 channel subunits are a molecular substrate for hypnotic actions of ketamine | journal = The Journal of Neuroscience | volume = 29 | issue = 3 | pages = 600–609 | date = January 2009 | pmid = 19158287 | pmc = 2744993 | doi = 10.1523/JNEUROSCI.3481-08.2009 }}{{cite journal | vauthors = Zhou C, Douglas JE, Kumar NN, Shu S, Bayliss DA, Chen X | title = Forebrain HCN1 channels contribute to hypnotic actions of ketamine | journal = Anesthesiology | volume = 118 | issue = 4 | pages = 785–795 | date = April 2013 | pmid = 23377220 | pmc = 3605219 | doi = 10.1097/ALN.0b013e318287b7c8 }}

• Propofol also inhibits HCN1.{{cite journal | vauthors = Bojak I, Day HC, Liley DT | title = Ketamine, Propofol, and the EEG: A Neural Field Analysis of HCN1-Mediated Interactions | journal = Frontiers in Computational Neuroscience | volume = 7 | issue = | pages = 22 | date = 2013 | pmid = 23576979 | pmc = 3617565 | doi = 10.3389/fncom.2013.00022 | doi-access = free }}

• Isoflurane and Sevoflurane inhibit HCN1.{{cite journal | vauthors = Zhou C, Liang P, Liu J, Ke B, Wang X, Li F, Li T, Bayliss DA, Chen X | display-authors = 6 | title = HCN1 Channels Contribute to the Effects of Amnesia and Hypnosis but not Immobility of Volatile Anesthetics | journal = Anesthesia and Analgesia | volume = 121 | issue = 3 | pages = 661–666 | date = September 2015 | pmid = 26287296 | pmc = 4544830 | doi = 10.1213/ANE.0000000000000830 }}

HCN1 has been shown to interact with HCN2.{{cite journal | vauthors = Much B, Wahl-Schott C, Zong X, Schneider A, Baumann L, Moosmang S, Ludwig A, Biel M | display-authors = 6 | title = Role of subunit heteromerization and N-linked glycosylation in the formation of functional hyperpolarization-activated cyclic nucleotide-gated channels | journal = The Journal of Biological Chemistry | volume = 278 | issue = 44 | pages = 43781–43786 | date = October 2003 | pmid = 12928435 | doi = 10.1074/jbc.M306958200 | doi-access = free }}{{cite journal | vauthors = Proenza C, Tran N, Angoli D, Zahynacz K, Balcar P, Accili EA | title = Different roles for the cyclic nucleotide binding domain and amino terminus in assembly and expression of hyperpolarization-activated, cyclic nucleotide-gated channels | journal = The Journal of Biological Chemistry | volume = 277 | issue = 33 | pages = 29634–29642 | date = August 2002 | pmid = 12034718 | doi = 10.1074/jbc.M200504200 | doi-access = free }}

De novo mutations in HCN1 cause epilepsy.{{cite journal | vauthors = Nava C, Dalle C, Rastetter A, Striano P, de Kovel CG, Nabbout R, Cancès C, Ville D, Brilstra EH, Gobbi G, Raffo E, Bouteiller D, Marie Y, Trouillard O, Robbiano A, Keren B, Agher D, Roze E, Lesage S, Nicolas A, Brice A, Baulac M, Vogt C, El Hajj N, Schneider E, Suls A, Weckhuysen S, Gormley P, Lehesjoki AE, De Jonghe P, Helbig I, Baulac S, Zara F, Koeleman BP, Haaf T, LeGuern E, Depienne C | display-authors = 6 | title = De novo mutations in HCN1 cause early infantile epileptic encephalopathy | journal = Nature Genetics | volume = 46 | issue = 6 | pages = 640–645 | date = June 2014 | pmid = 24747641 | doi = 10.1038/ng.2952 | s2cid = 861414 | url = https://hal.univ-lorraine.fr/hal-01710614/file/RASTETTER_Agn%C3%A8s.pdf }}

• Cyclic nucleotide-gated ion channel

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• {{cite journal | vauthors = Bonaldo MF, Lennon G, Soares MB | title = Normalization and subtraction: two approaches to facilitate gene discovery | journal = Genome Research | volume = 6 | issue = 9 | pages = 791–806 | date = September 1996 | pmid = 8889548 | doi = 10.1101/gr.6.9.791 | doi-access = free }}
• {{cite journal | vauthors = Ludwig A, Zong X, Jeglitsch M, Hofmann F, Biel M | title = A family of hyperpolarization-activated mammalian cation channels | journal = Nature | volume = 393 | issue = 6685 | pages = 587–591 | date = June 1998 | pmid = 9634236 | doi = 10.1038/31255 | s2cid = 4429453 | bibcode = 1998Natur.393..587L }}
• {{cite journal | vauthors = Kleiderlein JJ, Nisson PE, Jessee J, Li WB, Becker KG, Derby ML, Ross CA, Margolis RL | display-authors = 6 | title = CCG repeats in cDNAs from human brain | journal = Human Genetics | volume = 103 | issue = 6 | pages = 666–673 | date = December 1998 | pmid = 9921901 | doi = 10.1007/s004390050889 | s2cid = 23696667 }}
• {{cite journal | vauthors = Ulens C, Tytgat J | title = Functional heteromerization of HCN1 and HCN2 pacemaker channels | journal = The Journal of Biological Chemistry | volume = 276 | issue = 9 | pages = 6069–6072 | date = March 2001 | pmid = 11133998 | doi = 10.1074/jbc.C000738200 | doi-access = free }}
• {{cite journal | vauthors = Proenza C, Tran N, Angoli D, Zahynacz K, Balcar P, Accili EA | title = Different roles for the cyclic nucleotide binding domain and amino terminus in assembly and expression of hyperpolarization-activated, cyclic nucleotide-gated channels | journal = The Journal of Biological Chemistry | volume = 277 | issue = 33 | pages = 29634–29642 | date = August 2002 | pmid = 12034718 | doi = 10.1074/jbc.M200504200 | doi-access = free }}
• {{cite journal | vauthors = Chaplan SR, Guo HQ, Lee DH, Luo L, Liu C, Kuei C, Velumian AA, Butler MP, Brown SM, Dubin AE | display-authors = 6 | title = Neuronal hyperpolarization-activated pacemaker channels drive neuropathic pain | journal = The Journal of Neuroscience | volume = 23 | issue = 4 | pages = 1169–1178 | date = February 2003 | pmid = 12598605 | pmc = 6742242 | doi = 10.1523/JNEUROSCI.23-04-01169.2003 }}
• {{cite journal | vauthors = Lesso H, Li RA | title = Helical secondary structure of the external S3-S4 linker of pacemaker (HCN) channels revealed by site-dependent perturbations of activation phenotype | journal = The Journal of Biological Chemistry | volume = 278 | issue = 25 | pages = 22290–22297 | date = June 2003 | pmid = 12668666 | doi = 10.1074/jbc.M302466200 | doi-access = free }}
• {{cite journal | vauthors = Bender RA, Soleymani SV, Brewster AL, Nguyen ST, Beck H, Mathern GW, Baram TZ | title = Enhanced expression of a specific hyperpolarization-activated cyclic nucleotide-gated cation channel (HCN) in surviving dentate gyrus granule cells of human and experimental epileptic hippocampus | journal = The Journal of Neuroscience | volume = 23 | issue = 17 | pages = 6826–6836 | date = July 2003 | pmid = 12890777 | pmc = 3100807 | doi = 10.1523/JNEUROSCI.23-17-06826.2003 }}
• {{cite journal | vauthors = Much B, Wahl-Schott C, Zong X, Schneider A, Baumann L, Moosmang S, Ludwig A, Biel M | display-authors = 6 | title = Role of subunit heteromerization and N-linked glycosylation in the formation of functional hyperpolarization-activated cyclic nucleotide-gated channels | journal = The Journal of Biological Chemistry | volume = 278 | issue = 44 | pages = 43781–43786 | date = October 2003 | pmid = 12928435 | doi = 10.1074/jbc.M306958200 | doi-access = free }}
• {{cite journal | vauthors = He C, Chen F, Li B, Hu Z | title = Neurophysiology of HCN channels: from cellular functions to multiple regulations | journal = Progress in Neurobiology | volume = 112 | pages = 1–23 | date = January 2014 | pmid = 24184323 | doi = 10.1016/j.pneurobio.2013.10.001 | s2cid = 37519503 }}
• {{cite journal | vauthors = Wahl-Schott C, Fenske S, Biel M | title = HCN channels: new roles in sinoatrial node function | journal = Current Opinion in Pharmacology | volume = 15 | pages = 83–90 | date = April 2014 | pmid = 24441197 | doi = 10.1016/j.coph.2013.12.005 }}

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• {{MeshName|HCN1+protein,+human}}
• {{PDBe-KB2|O60741|Human Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1}}
• {{PDBe-KB2|O88704|Mouse Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1}}

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{{Ion channels|g4}}

Category:Ion channels

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