HCN1 | Cyclic nucleotide-regulated channels | IUPHAR/BPS Guide to PHARMACOLOGY

Top ▲

HCN1

Target id: 400

Nomenclature: HCN1

Family: Cyclic nucleotide-regulated channels

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for HCN1 in GtoImmuPdb

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 890 5p12 HCN1 hyperpolarization activated cyclic nucleotide gated potassium channel 1 48
Mouse 6 1 910 13 D2.3 Hcn1 hyperpolarization-activated, cyclic nucleotide-gated K+ 1 29,45
Rat 6 1 910 2q15 Hcn1 hyperpolarization-activated cyclic nucleotide-gated potassium channel 1 33
Previous and Unofficial Names
BCNG1 | HAC2 | hyperpolarization activated cyclic nucleotide-gated potassium channel 1 | hyperpolarization-activated, cyclic nucleotide-gated K+ 1 | hyperpolarization-activated
Database Links
CATH/Gene3D
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Structure of the human HCN1 hyperpolarization-activated cyclic nucleotide-gated ion channel in complex with cAMP
PDB Id:  5U6P
Ligand:  cyclic AMP   This ligand is endogenous
Resolution:  3.51Å
Species:  Human
References:  25
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
HCN2 35,56
HCN3 35
HCN4 35
Auxiliary Subunits
Name References
Trip8b 16,26-27,42,46,49-50,61
Other Associated Proteins
Name References
Protocadherin 15CD3 43-44
Filamin A 15
Ion Selectivity and Conductance
Species:  Human
Rank order:  K+ > Na+ [12.9 pS]
References:  31,53
Voltage Dependence
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -100.0 – -117.0 (median: -115.8) 98.0 – 290.0 8,20,58 Xenopus laevis oocyte Mouse
Inactivation  - -
Comments  Inside-out patch.
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -66.4 – -69.4 (median: -68.0) - 8 Xenopus laevis oocyte Mouse
Inactivation  - -
Comments  Intact oocytes.
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -70.0 – -90.0 (median: -80.0) 30.0 – 300.0 20,28,48,53 HEK 293 cells. Mouse
Inactivation  - -
Comments  Whole-cell, values are strongly influenced by experimental parameters, no voltage-dependent inactivation.
Activators (Human)
cyclic AMP > cyclic GMP (both weak)

Download all structure-activity data for this target as a CSV file

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
cyclic AMP Mm Agonist 7.2 pKd - -40.0 8,60
pKd 7.2 [8,60]
Holding voltage: -40.0 mV
Activator Comments
cAMP shifts V0.5 by +2 to +7 mV [1,8,53,60].
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
MEL57A Mm - 6.5 pEC50 - -80.0 10
pEC50 6.5 (EC50 3.2x10-7 M) [10]
Holding voltage: -80.0 mV
ivabradine Mm Antagonist 6.0 pIC50 - -35.0 4
pIC50 6.0 [4]
Holding voltage: -35.0 mV
cilobradine Hs Antagonist 5.9 pIC50 - -40.0 54
pIC50 5.9 [54]
Holding voltage: -40.0 mV
ivabradine Hs Antagonist 5.7 pIC50 - - 54
pIC50 5.7 (IC50 2.25x10-6 M) [54]
zatebradine Hs Antagonist 5.7 pIC50 - -40.0 54
pIC50 5.7 [54]
Holding voltage: -40.0 mV
propofol Mm - 5.2 pIC50 - -40.0 6,30
pIC50 5.2 [6,30]
Holding voltage: -40.0 mV
ZD7288 Hs Antagonist 4.7 pIC50 - - 53
pIC50 4.7 (IC50 2x10-5 M) [53]
clonidine Mm Antagonist 4.4 pIC50 - -40.0 22
pIC50 4.4 [22]
Holding voltage: -40.0 mV
Cs+ Hs Antagonist 3.7 pIC50 - -40.0 53
pIC50 3.7 (IC50 2.01x10-7 M) [53]
Holding voltage: -40.0 mV
Mg2+ Mm - 3.3 pIC50 - 50.0 57
pIC50 3.3 [57]
Holding voltage: 50.0 mV
View species-specific channel blocker tables
Channel Blocker Comments
Using HCN1 knockout mice, studies have shown that HCN1 contributes towards the hypnotic actions of the anaesthetics ketamine and isoflurane [9,64].
Tissue Distribution
Cochlear and vestibular hair cells.
Species:  Mouse
Technique:  Immunohistochemistry, patch clamp electrophysiology.
References:  18
Sino-atrial node, ventricle, atrium.
Species:  Mouse
Technique:  In situ hybridisation
References:  34
Pancreatic beta cells.
Species:  Mouse
Technique:  Voltage-clamp.
References:  13,63
Embryonic ventricle.
Species:  Mouse
Technique:  Quantitative PCR
References:  62
Urinary bladder.
Species:  Rat
Technique:  RT-PCR, Western blot.
References:  17
Brain.
Species:  Rat
Technique:  Immunohistochemistry
References:  40
Pancreatic beta cells.
Species:  Rat
Technique:  Voltage-clamp.
References:  13,63
Retina (bipolar cell bodies, type 5 bipolar cells).
Species:  Rat
Technique:  Immunohistochemistry
References:  36
Auditory brainstem and midbrain (ventral cochlear nucleus, principle neurons of the lateral and medial super olive, neurons of the ventral nucleus of the lateral lemniscus).
Species:  Rat
Technique:  Immunohistochemistry
References:  23
Neocortex, hippocampus, amygdala, diencephalon, thalamus, hypothalamus, substantia nigra, general motor system, auditory system, vestibular system, neurons of the ventral nucleus of the lateral lemniscus.
Species:  Rat
Technique:  In situ hybridisation
References:  33
Physiological Functions
Sour taste transduction.
Species:  Rat
Tissue:  Cells in slices of vallate papilla.
References:  52
Pacemaking and synaptic resetting in globus pallidus neurons (motor behaviour).
Species:  Mouse
Tissue:  Brain.
References:  7
Motor learning and neuronal integration by cerebellar Purkinje cells.
Species:  Mouse
Tissue:  Brain.
References:  39
Involvement in formation of spacial memory and plasticity.
Species:  Mouse
Tissue:  Brain.
References:  38
Processing of information from stellate neurons in layer II of the entorhinal cortex to the hippocampal dentate gyrus.
Species:  Mouse
Tissue:  Brain
References:  37
Controlling the time course of photoreceptors in response to bright light.
Species:  Mouse
Tissue:  Retina
References:  11
Involvement in neuropathic pain.
Species:  Rat
Tissue:  Peripheral nervous system.
References:  12,59
Spatial scaling in grid cells.
Species:  Mouse
Tissue:  Brain.
References:  14
Involvement in anxiety and depression related behaviour.
Species:  Rat
Tissue:  Brain
References:  21
Maintaining normal balance function.
Species:  Mouse
Tissue:  Inner ear
References:  19
Regulation of axon extension and glomerular formation in olfactory sensory neurons.
Species:  Mouse
Tissue:  Olfactory bulb
References:  32
Proper cone vision under mesopic conditions requires rapid adaptational feedback modulation of rod output via hyperpolarization-activated and cyclic nucleotide-gated channels 1 (HCN1).
Species:  Mouse
Tissue:  Retina
References:  51
Physiological Consequences of Altering Gene Expression
HCN1 knockout mice have increases seizure severity and seizure-related mortality.
Species:  Mouse
Tissue:  Brain
Technique:  Gene knockout
References:  47
Absence of HCN1 in retina affects shape and processing of light response.
Species:  Mouse
Tissue:  Retina
Technique:  Gene knockout
References:  11
Deletion of HCN1 causes profound motor learning and memory deficit in swimming and rotarod tasks.
Species:  Mouse
Tissue:  Cerebellar Purkinje cells.
Technique:  Knockout
References:  39
Knockdown of HCN1 in the dorsal hippocampus reduces anxiety- and depression-like behaviour.
Species:  Rat
Tissue:  Brain
Technique:  Gene klnockdown.
References:  21
HCN1-deficient mice have deficits in balance function.
Species:  Mouse
Tissue:  Inner ear
Technique:  Gene knockout
References:  19
Phenotypes, Alleles and Disease Models Mouse data from MGI

Show »

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Hcn1tm2Kndl Hcn1tm2Kndl/Hcn1tm2Kndl
involves: 129S/SvEv * C57BL/6
MGI:1096392  MP:0002807 abnormal eye blink conditioning behavior PMID: 14651847 
Hcn1tm2Kndl Hcn1tm2Kndl/Hcn1tm2Kndl
involves: 129S/SvEv * C57BL/6
MGI:1096392  MP:0001449 abnormal learning/ memory PMID: 14651847 
Hcn1tm2Kndl Hcn1tm2Kndl/Hcn1tm2Kndl
involves: 129S/SvEv * C57BL/6
MGI:1096392  MP:0002804 abnormal motor learning PMID: 14651847 
Hcn1tm2Kndl Hcn1tm2Kndl/Hcn1tm2Kndl
involves: 129S/SvEv * C57BL/6
MGI:1096392  MP:0001463 abnormal spatial learning PMID: 14651847 
Hcn1tm2Kndl Hcn1tm2Kndl/Hcn1tm2Kndl
involves: 129S/SvEv * C57BL/6
MGI:1096392  MP:0002797 increased thigmotaxis PMID: 14651847 
Hcn1tm1Kndl Hcn1tm1Kndl/Hcn1tm1Kndl
involves: 129S/SvEv * C57BL/6
MGI:1096392  MP:0002169 no abnormal phenotype detected PMID: 14651847 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Epilepsy
Role: 
References:  2,55
Disease:  Epileptic encephalopathy, early infantile, 24; EIEE24
Synonyms: Early infantile epileptic encephalopathy [Orphanet: ORPHA1934]
Infantile epileptic encephalopathy [Disease Ontology: DOID:2481]
Disease Ontology: DOID:2481
OMIM: 615871
Orphanet: ORPHA1934
Gene Expression and Pathophysiology
Decline of HCN1 expression correlates with the onset of seizures in WAG/Rij rats.
Tissue or cell type:  Apical dendrites of layer 5 pyramidal neurons in the cortex.
Pathophysiology:  Absence epilepsy.
Species:  Rat
Technique: 
References:  24
Downregulation of HCN1 in CA1 of Gabra5-/- mice.
Tissue or cell type:  CA1 of hippocampus.
Pathophysiology: 
Species:  Mouse
Technique: 
References:  3
Downregulation of HCN1 in human temporal lobe epilepsy (TLE) and the rat pilocarpine model of TLE.
Tissue or cell type:  Dentate gyrus.
Pathophysiology:  Temporal lobe epilepsy.
Species:  Rat
Technique: 
References:  55
Increase in HCN1 expression in the thalamocortical neurons of epileptic rats (WAG/Rij).
Tissue or cell type:  Thalamocortical neuons.
Pathophysiology:  Absence epilepsy.
Species:  Rat
Technique: 
References:  5
Upregulation of HCN1 in the ventral-lateral periaqueductal gray in a chronic constriction injury model.
Tissue or cell type:  Ventral-lateral periaqueductal gray.
Pathophysiology:  Neuropathic pain.
Species:  Rat
Technique: 
References:  12
Alteration of HCN1 expression in the hippocampus following pilocarpine-induced status epilepticus.
Tissue or cell type:  Hippocampus.
Pathophysiology:  Status epilepsy.
Species:  Rat
Technique: 
References:  41

References

Show »

1. Altomare C, Terragni B, Brioschi C, Milanesi R, Pagliuca C, Viscomi C, Moroni A, Baruscotti M, DiFrancesco D. (2003) Heteromeric HCN1-HCN4 channels: a comparison with native pacemaker channels from the rabbit sinoatrial node. J. Physiol. (Lond.), 549 (Pt 2): 347-59. [PMID:12702747]

2. Bender RA, Soleymani SV, Brewster AL, Nguyen ST, Beck H, Mathern GW, Baram TZ. (2003) 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. J. Neurosci., 23 (17): 6826-36. [PMID:12890777]

3. Bonin RP, Zurek AA, Yu J, Bayliss DA, Orser BA. (2013) Hyperpolarization-activated current (In) is reduced in hippocampal neurons from Gabra5-/- mice. PLoS ONE, 8 (3): e58679. [PMID:23516534]

4. Bucchi A, Tognati A, Milanesi R, Baruscotti M, DiFrancesco D. (2006) Properties of ivabradine-induced block of HCN1 and HCN4 pacemaker channels. J. Physiol. (Lond.), 572 (Pt 2): 335-46. [PMID:16484306]

5. Budde T, Caputi L, Kanyshkova T, Staak R, Abrahamczik C, Munsch T, Pape HC. (2005) Impaired regulation of thalamic pacemaker channels through an imbalance of subunit expression in absence epilepsy. J. Neurosci., 25 (43): 9871-82. [PMID:16251434]

6. Cacheaux LP, Topf N, Tibbs GR, Schaefer UR, Levi R, Harrison NL, Abbott GW, Goldstein PA. (2005) Impairment of hyperpolarization-activated, cyclic nucleotide-gated channel function by the intravenous general anesthetic propofol. J. Pharmacol. Exp. Ther., 315 (2): 517-25. [PMID:16033909]

7. Chan CS, Shigemoto R, Mercer JN, Surmeier DJ. (2004) HCN2 and HCN1 channels govern the regularity of autonomous pacemaking and synaptic resetting in globus pallidus neurons. J. Neurosci., 24 (44): 9921-32. [PMID:15525777]

8. Chen S, Wang J, Siegelbaum SA. (2001) Properties of hyperpolarization-activated pacemaker current defined by coassembly of HCN1 and HCN2 subunits and basal modulation by cyclic nucleotide. J. Gen. Physiol., 117 (5): 491-504. [PMID:11331358]

9. Chen X, Shu S, Kennedy DP, Willcox SC, Bayliss DA. (2009) Subunit-specific effects of isoflurane on neuronal Ih in HCN1 knockout mice. J. Neurophysiol., 101 (1): 129-40. [PMID:18971302]

10. Del Lungo M, Melchiorre M, Guandalini L, Sartiani L, Mugelli A, Koncz I, Szel T, Varro A, Romanelli MN, Cerbai E. (2012) Novel blockers of hyperpolarization-activated current with isoform selectivity in recombinant cells and native tissue. Br. J. Pharmacol., 166 (2): 602-16. [PMID:22091830]

11. Della Santina L, Piano I, Cangiano L, Caputo A, Ludwig A, Cervetto L, Gargini C. (2012) Processing of retinal signals in normal and HCN deficient mice. PLoS ONE, 7 (1): e29812. [PMID:22279546]

12. Du L, Wang SJ, Cui J, He WJ, Ruan HZ. (2013) Inhibition of HCN channels within the periaqueductal gray attenuates neuropathic pain in rats. Behav. Neurosci., 127 (2): 325-9. [PMID:23398435]

13. El-Kholy W, MacDonald PE, Fox JM, Bhattacharjee A, Xue T, Gao X, Zhang Y, Stieber J, Li RA, Tsushima RG et al.. (2007) Hyperpolarization-activated cyclic nucleotide-gated channels in pancreatic beta-cells. Mol. Endocrinol., 21 (3): 753-64. [PMID:17158221]

14. Giocomo LM, Hussaini SA, Zheng F, Kandel ER, Moser MB, Moser EI. (2011) Grid cells use HCN1 channels for spatial scaling. Cell, 147 (5): 1159-70. [PMID:22100643]

15. Gravante B, Barbuti A, Milanesi R, Zappi I, Viscomi C, DiFrancesco D. (2004) Interaction of the pacemaker channel HCN1 with filamin A. J. Biol. Chem., 279 (42): 43847-53. [PMID:15292205]

16. Han Y, Noam Y, Lewis AS, Gallagher JJ, Wadman WJ, Baram TZ, Chetkovich DM. (2011) Trafficking and gating of hyperpolarization-activated cyclic nucleotide-gated channels are regulated by interaction with tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b) and cyclic AMP at distinct sites. J. Biol. Chem., 286 (23): 20823-34. [PMID:21504900]

17. He P, Deng J, Zhong X, Zhou Z, Song B, Li L. (2012) Identification of a hyperpolarization-activated cyclic nucleotide-gated channel and its subtypes in the urinary bladder of the rat. Urology, 79 (6): 1411.e7-13. [PMID:22446339]

18. Horwitz GC, Lelli A, Géléoc GS, Holt JR. (2010) HCN channels are not required for mechanotransduction in sensory hair cells of the mouse inner ear. PLoS ONE, 5 (1): e8627. [PMID:20062532]

19. Horwitz GC, Risner-Janiczek JR, Jones SM, Holt JR. (2011) HCN channels expressed in the inner ear are necessary for normal balance function. J. Neurosci., 31 (46): 16814-25. [PMID:22090507]

20. Kaupp UB, Seifert R. (2001) Molecular diversity of pacemaker ion channels. Annu. Rev. Physiol., 63: 235-57. [PMID:11181956]

21. Kim CS, Chang PY, Johnston D. (2012) Enhancement of dorsal hippocampal activity by knockdown of HCN1 channels leads to anxiolytic- and antidepressant-like behaviors. Neuron, 75 (3): 503-16. [PMID:22884333]

22. Knaus A, Zong X, Beetz N, Jahns R, Lohse MJ, Biel M, Hein L. (2007) Direct inhibition of cardiac hyperpolarization-activated cyclic nucleotide-gated pacemaker channels by clonidine. Circulation, 115 (7): 872-80. [PMID:17261653]

23. Koch U, Braun M, Kapfer C, Grothe B. (2004) Distribution of HCN1 and HCN2 in rat auditory brainstem nuclei. Eur. J. Neurosci., 20 (1): 79-91. [PMID:15245481]

24. Kole MH, Bräuer AU, Stuart GJ. (2007) Inherited cortical HCN1 channel loss amplifies dendritic calcium electrogenesis and burst firing in a rat absence epilepsy model. J. Physiol. (Lond.), 578 (Pt 2): 507-25. [PMID:17095562]

25. Lee CH, MacKinnon R. (2017) Structures of the Human HCN1 Hyperpolarization-Activated Channel. Cell, 168 (1-2): 111-120.e11. [PMID:28086084]

26. Lewis AS, Schwartz E, Chan CS, Noam Y, Shin M, Wadman WJ, Surmeier DJ, Baram TZ, Macdonald RL, Chetkovich DM. (2009) Alternatively spliced isoforms of TRIP8b differentially control h channel trafficking and function. J. Neurosci., 29 (19): 6250-65. [PMID:19439603]

27. Lewis AS, Vaidya SP, Blaiss CA, Liu Z, Stoub TR, Brager DH, Chen X, Bender RA, Estep CM, Popov AB et al.. (2011) Deletion of the hyperpolarization-activated cyclic nucleotide-gated channel auxiliary subunit TRIP8b impairs hippocampal Ih localization and function and promotes antidepressant behavior in mice. J. Neurosci., 31 (20): 7424-40. [PMID:21593326]

28. Ludwig A, Zong X, Hofmann F, Biel M. (1999) Structure and function of cardiac pacemaker channels. Cell. Physiol. Biochem., 9 (4-5): 179-86. [PMID:10575196]

29. Ludwig A, Zong X, Jeglitsch M, Hofmann F, Biel M. (1998) A family of hyperpolarization-activated mammalian cation channels. Nature, 393 (6685): 587-91. [PMID:9634236]

30. Lyashchenko AK, Redd KJ, Yang J, Tibbs GR. (2007) Propofol inhibits HCN1 pacemaker channels by selective association with the closed states of the membrane embedded channel core. J. Physiol. (Lond.), 583 (Pt 1): 37-56. [PMID:17569731]

31. Michels G, Er F, Khan I, Südkamp M, Herzig S, Hoppe UC. (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. [PMID:15687126]

32. Mobley AS, Miller AM, Araneda RC, Maurer LR, Müller F, Greer CA. (2010) Hyperpolarization-activated cyclic nucleotide-gated channels in olfactory sensory neurons regulate axon extension and glomerular formation. J. Neurosci., 30 (49): 16498-508. [PMID:21147989]

33. Monteggia LM, Eisch AJ, Tang MD, Kaczmarek LK, Nestler EJ. (2000) Cloning and localization of the hyperpolarization-activated cyclic nucleotide-gated channel family in rat brain. Brain Res. Mol. Brain Res., 81 (1-2): 129-39. [PMID:11000485]

34. Moosmang S, Stieber J, Zong X, Biel M, Hofmann F, Ludwig A. (2001) Cellular expression and functional characterization of four hyperpolarization-activated pacemaker channels in cardiac and neuronal tissues. Eur. J. Biochem., 268 (6): 1646-52. [PMID:11248683]

35. Much B, Wahl-Schott C, Zong X, Schneider A, Baumann L, Moosmang S, Ludwig A, Biel M. (2003) Role of subunit heteromerization and N-linked glycosylation in the formation of functional hyperpolarization-activated cyclic nucleotide-gated channels. J. Biol. Chem., 278 (44): 43781-6. [PMID:12928435]

36. Müller F, Scholten A, Ivanova E, Haverkamp S, Kremmer E, Kaupp UB. (2003) HCN channels are expressed differentially in retinal bipolar cells and concentrated at synaptic terminals. Eur. J. Neurosci., 17 (10): 2084-96. [PMID:12786975]

37. Nolan MF, Dudman JT, Dodson PD, Santoro B. (2007) HCN1 channels control resting and active integrative properties of stellate cells from layer II of the entorhinal cortex. J. Neurosci., 27 (46): 12440-51. [PMID:18003822]

38. Nolan MF, Malleret G, Dudman JT, Buhl DL, Santoro B, Gibbs E, Vronskaya S, Buzsáki G, Siegelbaum SA, Kandel ER, Morozov A. (2004) A behavioral role for dendritic integration: HCN1 channels constrain spatial memory and plasticity at inputs to distal dendrites of CA1 pyramidal neurons. Cell, 119 (5): 719-32. [PMID:15550252]

39. Nolan MF, Malleret G, Lee KH, Gibbs E, Dudman JT, Santoro B, Yin D, Thompson RF, Siegelbaum SA, Kandel ER, Morozov A. (2003) The hyperpolarization-activated HCN1 channel is important for motor learning and neuronal integration by cerebellar Purkinje cells. Cell, 115 (5): 551-64. [PMID:14651847]

40. Notomi T, Shigemoto R. (2004) Immunohistochemical localization of Ih channel subunits, HCN1-4, in the rat brain. J. Comp. Neurol., 471 (3): 241-76. [PMID:14991560]

41. Oh YJ, Na J, Jeong JH, Park DK, Park KH, Ko JS, Kim DS. (2012) Alterations in hyperpolarization-activated cyclic nucleotidegated cation channel (HCN) expression in the hippocampus following pilocarpine-induced status epilepticus. BMB Rep, 45 (11): 635-40. [PMID:23187002]

42. Piskorowski R, Santoro B, Siegelbaum SA. (2011) TRIP8b splice forms act in concert to regulate the localization and expression of HCN1 channels in CA1 pyramidal neurons. Neuron, 70 (3): 495-509. [PMID:21555075]

43. Ramakrishnan NA, Drescher MJ, Barretto RL, Beisel KW, Hatfield JS, Drescher DG. (2009) Calcium-dependent binding of HCN1 channel protein to hair cell stereociliary tip link protein protocadherin 15 CD3. J. Biol. Chem., 284 (5): 3227-38. [PMID:19008224]

44. Ramakrishnan NA, Drescher MJ, Khan KM, Hatfield JS, Drescher DG. (2012) HCN1 and HCN2 proteins are expressed in cochlear hair cells: HCN1 can form a ternary complex with protocadherin 15 CD3 and F-actin-binding filamin A or can interact with HCN2. J. Biol. Chem., 287 (45): 37628-46. [PMID:22948144]

45. Santoro B, Grant SG, Bartsch D, Kandel ER. (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. Proc. Natl. Acad. Sci. U.S.A., 94 (26): 14815-20. [PMID:9405696]

46. Santoro B, Hu L, Liu H, Saponaro A, Pian P, Piskorowski RA, Moroni A, Siegelbaum SA. (2011) TRIP8b regulates HCN1 channel trafficking and gating through two distinct C-terminal interaction sites. J. Neurosci., 31 (11): 4074-86. [PMID:21411649]

47. Santoro B, Lee JY, Englot DJ, Gildersleeve S, Piskorowski RA, Siegelbaum SA, Winawer MR, Blumenfeld H. (2010) Increased seizure severity and seizure-related death in mice lacking HCN1 channels. Epilepsia, 51 (8): 1624-7. [PMID:20384728]

48. Santoro B, Liu DT, Yao H, Bartsch D, Kandel ER, Siegelbaum SA, Tibbs GR. (1998) Identification of a gene encoding a hyperpolarization-activated pacemaker channel of brain. Cell, 93 (5): 717-29. [PMID:9630217]

49. Santoro B, Piskorowski RA, Pian P, Hu L, Liu H, Siegelbaum SA. (2009) TRIP8b splice variants form a family of auxiliary subunits that regulate gating and trafficking of HCN channels in the brain. Neuron, 62 (6): 802-13. [PMID:19555649]

50. Santoro B, Wainger BJ, Siegelbaum SA. (2004) Regulation of HCN channel surface expression by a novel C-terminal protein-protein interaction. J. Neurosci., 24 (47): 10750-62. [PMID:15564593]

51. Seeliger MW, Brombas A, Weiler R, Humphries P, Knop G, Tanimoto N, Müller F. (2011) Modulation of rod photoreceptor output by HCN1 channels is essential for regular mesopic cone vision. Nat Commun, 2: 532. [PMID:22068599]

52. Stevens DR, Seifert R, Bufe B, Müller F, Kremmer E, Gauss R, Meyerhof W, Kaupp UB, Lindemann B. (2001) Hyperpolarization-activated channels HCN1 and HCN4 mediate responses to sour stimuli. Nature, 413 (6856): 631-5. [PMID:11675786]

53. Stieber J, Stöckl G, Herrmann S, Hassfurth B, Hofmann F. (2005) Functional expression of the human HCN3 channel. J. Biol. Chem., 280 (41): 34635-43. [PMID:16043489]

54. Stieber J, Wieland K, Stöckl G, Ludwig A, Hofmann F. (2006) Bradycardic and proarrhythmic properties of sinus node inhibitors. Mol. Pharmacol., 69 (4): 1328-37. [PMID:16387796]

55. Surges R, Kukley M, Brewster A, Rüschenschmidt C, Schramm J, Baram TZ, Beck H, Dietrich D. (2012) Hyperpolarization-activated cation current Ih of dentate gyrus granule cells is upregulated in human and rat temporal lobe epilepsy. Biochem. Biophys. Res. Commun., 420 (1): 156-60. [PMID:22405820]

56. Ulens C, Tytgat J. (2001) Functional heteromerization of HCN1 and HCN2 pacemaker channels. J. Biol. Chem., 276 (9): 6069-72. [PMID:11133998]

57. Vemana S, Pandey S, Larsson HP. (2008) Intracellular Mg2+ is a voltage-dependent pore blocker of HCN channels. Am. J. Physiol., Cell Physiol., 295 (2): C557-65. [PMID:18579800]

58. Wainger BJ, DeGennaro M, Santoro B, Siegelbaum SA, Tibbs GR. (2001) Molecular mechanism of cAMP modulation of HCN pacemaker channels. Nature, 411 (6839): 805-10. [PMID:11459060]

59. Wan Y. (2008) Involvement of hyperpolarization-activated, cyclic nucleotide-gated cation channels in dorsal root ganglion in neuropathic pain. Sheng Li Xue Bao, 60 (5): 579-80. [PMID:18958363]

60. Wang J, Chen S, Siegelbaum SA. (2001) Regulation of hyperpolarization-activated HCN channel gating and cAMP modulation due to interactions of COOH terminus and core transmembrane regions. J. Gen. Physiol., 118 (3): 237-50. [PMID:11524455]

61. Wilkars W, Liu Z, Lewis AS, Stoub TR, Ramos EM, Brandt N, Nicholson DA, Chetkovich DM, Bender RA. (2012) Regulation of axonal HCN1 trafficking in perforant path involves expression of specific TRIP8b isoforms. PLoS ONE, 7 (2): e32181. [PMID:22363812]

62. Yasui K, Liu W, Opthof T, Kada K, Lee JK, Kamiya K, Kodama I. (2001) I(f) current and spontaneous activity in mouse embryonic ventricular myocytes. Circ. Res., 88 (5): 536-42. [PMID:11249878]

63. Zhang Y, Liu Y, Qu J, Hardy A, Zhang N, Diao J, Strijbos PJ, Tsushima R, Robinson RB, Gaisano HY et al.. (2009) Functional characterization of hyperpolarization-activated cyclic nucleotide-gated channels in rat pancreatic beta cells. J. Endocrinol., 203 (1): 45-53. [PMID:19654142]

64. Zhou C, Douglas JE, Kumar NN, Shu S, Bayliss DA, Chen X. (2013) Forebrain HCN1 channels contribute to hypnotic actions of ketamine. Anesthesiology, 118 (4): 785-95. [PMID:23377220]

Contributors

Show »

How to cite this page

Verena Hammelmann, Martin Biel.
Cyclic nucleotide-regulated channels: HCN1. Last modified on 10/03/2017. Accessed on 21/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=400.