HCN1

HCN1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	3U0Z
Identifiers
Aliases	HCN1, BCNG-1, BCNG1, EIEE24, HAC-2, hyperpolarization activated cyclic nucleotide gated potassium channel 1, GEFSP10, DEE24
External IDs	OMIM: 602780; MGI: 1096392; HomoloGene: 32093; GeneCards: HCN1; OMA:HCN1 - orthologs
Gene location (Human)
Chr.	Chromosome 5 (human)
End	45,696,498 bp
Gene location (Mouse)
Chr.	Chromosome 13 (mouse)
End	118,123,954 bp
RNA expression pattern
	Top expressed in
	endothelial cell; ; Brodmann area 23; ; primary visual cortex; ; trigeminal ganglion; ; Brodmann area 46; ; spinal ganglia; ; prefrontal cortex; ; superior frontal gyrus; ; middle temporal gyrus; ; Parietal Lobe;
	Top expressed in
	subiculum; ; medial vestibular nucleus; ; pontine nuclei; ; deep cerebellar nuclei; ; cerebellar vermis; ; facial motor nucleus; ; lobe of cerebellum; ; lumbar spinal ganglion; ; anterior horn of spinal cord; ; inferior colliculi;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	nucleotide binding; intracellular cAMP-activated cation channel activity; identical protein binding; voltage-gated sodium channel activity; ion channel activity; potassium channel activity; sodium channel activity; voltage-gated ion channel activity; voltage-gated potassium channel activity; voltage-gated cation channel activity; cAMP binding; protein binding;
Cellular component	axon; membrane; dendrite; plasma membrane; integral component of membrane; HCN channel complex; integral component of plasma membrane;
Biological process	transmembrane transport; retinal cone cell development; regulation of ion transmembrane transport; apical protein localization; ion transport; sodium ion transport; regulation of membrane potential; sodium ion transmembrane transport; potassium ion transmembrane transport; potassium ion transport; protein homotetramerization; cellular response to cAMP;
	Sources:Amigo / QuickGO
Orthologs
	348980
	15165
	ENSG00000164588
	ENSMUSG00000021730
	O60741
	O88704
	NM_021072
	NM_010408
	NP_066550
	NP_034538
	Wikidata
View/Edit Human	View/Edit Mouse

Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 is a protein that in humans is encoded by the HCN1 gene.^[5]^[6]^[7]^[8]

Function

Hyperpolarization-activated cation channels of the HCN gene family, such as HCN1, contribute to spontaneous rhythmic activity in both heart and brain.^[8]

Tissue distribution

HCN1 channel expression is found in the sinoatrial node,^[9]^[10] the neocortex, hippocampus, cerebellar cortex, dorsal root ganglion, trigeminal ganglion and brainstem.^[11]^[12]^[13]^[14]^[15]

Ligands

Ketamine is an inhibitor of HCN1 in addition to its other targets.^[16]^[17]

Propofol also inhibits HCN1.^[18]

Isoflurane and Sevoflurane inhibit HCN1.^[19]

Interactions

HCN1 has been shown to interact with HCN2.^[20]^[21]

Epilepsy

De novo mutations in HCN1 cause epilepsy.^[22]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000164588 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000021730 – 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.
^ Santoro B, Grant SG, Bartsch D, Kandel ER (December 1997). "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". Proceedings of the National Academy of Sciences of the United States of America. 94 (26): 14815–14820. Bibcode:1997PNAS...9414815S. doi:10.1073/pnas.94.26.14815. PMC 25120. PMID 9405696.
^ Santoro B, Liu DT, Yao H, Bartsch D, Kandel ER, Siegelbaum SA, Tibbs GR (May 1998). "Identification of a gene encoding a hyperpolarization-activated pacemaker channel of brain". Cell. 93 (5): 717–729. doi:10.1016/S0092-8674(00)81434-8. PMID 9630217.
^ Hofmann F, Biel M, Kaupp UB (December 2005). "International Union of Pharmacology. LI. Nomenclature and structure-function relationships of cyclic nucleotide-regulated channels". Pharmacological Reviews. 57 (4): 455–462. doi:10.1124/pr.57.4.8. PMID 16382102. S2CID 45853869.
^ ^a ^b "Entrez Gene: HCN1 hyperpolarization activated cyclic nucleotide-gated potassium channel 1".
^ Marionneau C, Couette B, Liu J, Li H, Mangoni ME, Nargeot J, et al. (January 2005). "Specific pattern of ionic channel gene expression associated with pacemaker activity in the mouse heart". The Journal of Physiology. 562 (Pt 1): 223–234. doi:10.1113/jphysiol.2004.074047. PMC 1665484. PMID 15498808.
^ Shi W, Wymore R, Yu H, Wu J, Wymore RT, Pan Z, et al. (July 1999). "Distribution and prevalence of hyperpolarization-activated cation channel (HCN) mRNA expression in cardiac tissues". Circulation Research. 85 (1): e1 – e6. doi:10.1161/01.RES.85.1.e1. PMID 10400919.
^ Lörincz A, Notomi T, Tamás G, Shigemoto R, Nusser Z (November 2002). "Polarized and compartment-dependent distribution of HCN1 in pyramidal cell dendrites". Nature Neuroscience. 5 (11): 1185–1193. doi:10.1038/nn962. PMID 12389030. S2CID 18132966.
^ Milligan CJ, Edwards IJ, Deuchars J (April 2006). "HCN1 ion channel immunoreactivity in spinal cord and medulla oblongata". Brain Research. 1081 (1): 79–91. doi:10.1016/j.brainres.2006.01.019. PMID 16503331. S2CID 30929772.
^ Moosmang S, Biel M, Hofmann F, Ludwig A (1999). "Differential distribution of four hyperpolarization-activated cation channels in mouse brain". Biological Chemistry. 380 (7–8): 975–980. doi:10.1515/BC.1999.121. PMID 10494850. S2CID 22722872.
^ Wells JE, Rowland KC, Proctor EK (September 2007). "Hyperpolarization-activated channels in trigeminal ganglia innervating healthy and pulp-exposed teeth". International Endodontic Journal. 40 (9): 715–721. doi:10.1111/j.1365-2591.2007.01297.x. PMID 17645513.
^ Santoro B, Grant SG, Bartsch D, Kandel ER (December 1997). "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". Proceedings of the National Academy of Sciences of the United States of America. 94 (26): 14815–14820. Bibcode:1997PNAS...9414815S. doi:10.1073/pnas.94.26.14815. PMC 25120. PMID 9405696.
^ Chen X, Shu S, Bayliss DA (January 2009). "HCN1 channel subunits are a molecular substrate for hypnotic actions of ketamine". The Journal of Neuroscience. 29 (3): 600–609. doi:10.1523/JNEUROSCI.3481-08.2009. PMC 2744993. PMID 19158287.
^ Zhou C, Douglas JE, Kumar NN, Shu S, Bayliss DA, Chen X (April 2013). "Forebrain HCN1 channels contribute to hypnotic actions of ketamine". Anesthesiology. 118 (4): 785–795. doi:10.1097/ALN.0b013e318287b7c8. PMC 3605219. PMID 23377220.
^ Bojak I, Day HC, Liley DT (2013). "Ketamine, Propofol, and the EEG: A Neural Field Analysis of HCN1-Mediated Interactions". Frontiers in Computational Neuroscience. 7: 22. doi:10.3389/fncom.2013.00022. PMC 3617565. PMID 23576979.
^ Zhou C, Liang P, Liu J, Ke B, Wang X, Li F, et al. (September 2015). "HCN1 Channels Contribute to the Effects of Amnesia and Hypnosis but not Immobility of Volatile Anesthetics". Anesthesia and Analgesia. 121 (3): 661–666. doi:10.1213/ANE.0000000000000830. PMC 4544830. PMID 26287296.
^ Much B, Wahl-Schott C, Zong X, Schneider A, Baumann L, Moosmang S, et al. (October 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): 43781–43786. doi:10.1074/jbc.M306958200. PMID 12928435.
^ Proenza C, Tran N, Angoli D, Zahynacz K, Balcar P, Accili EA (August 2002). "Different roles for the cyclic nucleotide binding domain and amino terminus in assembly and expression of hyperpolarization-activated, cyclic nucleotide-gated channels". The Journal of Biological Chemistry. 277 (33): 29634–29642. doi:10.1074/jbc.M200504200. PMID 12034718.
^ Nava C, Dalle C, Rastetter A, Striano P, de Kovel CG, Nabbout R, et al. (June 2014). "De novo mutations in HCN1 cause early infantile epileptic encephalopathy" (PDF). Nature Genetics. 46 (6): 640–645. doi:10.1038/ng.2952. PMID 24747641. S2CID 861414.

External links

HCN1+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
Overview of all the structural information available in the PDB for UniProt: O60741 (Human Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1) at the PDBe-KB.
Overview of all the structural information available in the PDB for UniProt: O88704 (Mouse Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1) at the PDBe-KB.

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

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[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000164588 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000021730 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid9405696-5] Santoro B, Grant SG, Bartsch D, Kandel ER (December 1997). "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". Proceedings of the National Academy of Sciences of the United States of America. 94 (26): 14815–14820. Bibcode:1997PNAS...9414815S. doi:10.1073/pnas.94.26.14815. PMC 25120. PMID 9405696.

[pmid9630217-6] Santoro B, Liu DT, Yao H, Bartsch D, Kandel ER, Siegelbaum SA, Tibbs GR (May 1998). "Identification of a gene encoding a hyperpolarization-activated pacemaker channel of brain". Cell. 93 (5): 717–729. doi:10.1016/S0092-8674(00)81434-8. PMID 9630217.

[pmid16382102-7] Hofmann F, Biel M, Kaupp UB (December 2005). "International Union of Pharmacology. LI. Nomenclature and structure-function relationships of cyclic nucleotide-regulated channels". Pharmacological Reviews. 57 (4): 455–462. doi:10.1124/pr.57.4.8. PMID 16382102. S2CID 45853869.

[entrez-8] "Entrez Gene: HCN1 hyperpolarization activated cyclic nucleotide-gated potassium channel 1".

[MarionneauCouette2005-9] Marionneau C, Couette B, Liu J, Li H, Mangoni ME, Nargeot J, et al. (January 2005). "Specific pattern of ionic channel gene expression associated with pacemaker activity in the mouse heart". The Journal of Physiology. 562 (Pt 1): 223–234. doi:10.1113/jphysiol.2004.074047. PMC 1665484. PMID 15498808.

[ShiWymore1999-10] Shi W, Wymore R, Yu H, Wu J, Wymore RT, Pan Z, et al. (July 1999). "Distribution and prevalence of hyperpolarization-activated cation channel (HCN) mRNA expression in cardiac tissues". Circulation Research. 85 (1): e1 – e6. doi:10.1161/01.RES.85.1.e1. PMID 10400919.

[LörinczNotomi2002-11] Lörincz A, Notomi T, Tamás G, Shigemoto R, Nusser Z (November 2002). "Polarized and compartment-dependent distribution of HCN1 in pyramidal cell dendrites". Nature Neuroscience. 5 (11): 1185–1193. doi:10.1038/nn962. PMID 12389030. S2CID 18132966.

[MilliganEdwards2006-12] Milligan CJ, Edwards IJ, Deuchars J (April 2006). "HCN1 ion channel immunoreactivity in spinal cord and medulla oblongata". Brain Research. 1081 (1): 79–91. doi:10.1016/j.brainres.2006.01.019. PMID 16503331. S2CID 30929772.

[MoosmangBiel1999-13] Moosmang S, Biel M, Hofmann F, Ludwig A (1999). "Differential distribution of four hyperpolarization-activated cation channels in mouse brain". Biological Chemistry. 380 (7–8): 975–980. doi:10.1515/BC.1999.121. PMID 10494850. S2CID 22722872.

[WellsRowland2007-14] Wells JE, Rowland KC, Proctor EK (September 2007). "Hyperpolarization-activated channels in trigeminal ganglia innervating healthy and pulp-exposed teeth". International Endodontic Journal. 40 (9): 715–721. doi:10.1111/j.1365-2591.2007.01297.x. PMID 17645513.

[15] Santoro B, Grant SG, Bartsch D, Kandel ER (December 1997). "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". Proceedings of the National Academy of Sciences of the United States of America. 94 (26): 14815–14820. Bibcode:1997PNAS...9414815S. doi:10.1073/pnas.94.26.14815. PMC 25120. PMID 9405696.

[pmid19158287-16] Chen X, Shu S, Bayliss DA (January 2009). "HCN1 channel subunits are a molecular substrate for hypnotic actions of ketamine". The Journal of Neuroscience. 29 (3): 600–609. doi:10.1523/JNEUROSCI.3481-08.2009. PMC 2744993. PMID 19158287.

[pmid23377220-17] Zhou C, Douglas JE, Kumar NN, Shu S, Bayliss DA, Chen X (April 2013). "Forebrain HCN1 channels contribute to hypnotic actions of ketamine". Anesthesiology. 118 (4): 785–795. doi:10.1097/ALN.0b013e318287b7c8. PMC 3605219. PMID 23377220.

[pmid23576979-18] Bojak I, Day HC, Liley DT (2013). "Ketamine, Propofol, and the EEG: A Neural Field Analysis of HCN1-Mediated Interactions". Frontiers in Computational Neuroscience. 7: 22. doi:10.3389/fncom.2013.00022. PMC 3617565. PMID 23576979.

[pmid26287296-19] Zhou C, Liang P, Liu J, Ke B, Wang X, Li F, et al. (September 2015). "HCN1 Channels Contribute to the Effects of Amnesia and Hypnosis but not Immobility of Volatile Anesthetics". Anesthesia and Analgesia. 121 (3): 661–666. doi:10.1213/ANE.0000000000000830. PMC 4544830. PMID 26287296.

[pmid12928435-20] Much B, Wahl-Schott C, Zong X, Schneider A, Baumann L, Moosmang S, et al. (October 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): 43781–43786. doi:10.1074/jbc.M306958200. PMID 12928435.

[pmid12034718-21] Proenza C, Tran N, Angoli D, Zahynacz K, Balcar P, Accili EA (August 2002). "Different roles for the cyclic nucleotide binding domain and amino terminus in assembly and expression of hyperpolarization-activated, cyclic nucleotide-gated channels". The Journal of Biological Chemistry. 277 (33): 29634–29642. doi:10.1074/jbc.M200504200. PMID 12034718.

[pmid24747641-22] Nava C, Dalle C, Rastetter A, Striano P, de Kovel CG, Nabbout R, et al. (June 2014). "De novo mutations in HCN1 cause early infantile epileptic encephalopathy" (PDF). Nature Genetics. 46 (6): 640–645. doi:10.1038/ng.2952. PMID 24747641. S2CID 861414.

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