HCN2 | Cyclic nucleotide-regulated channels | IUPHAR/BPS Guide to PHARMACOLOGY

HCN2

Target id: 401

Nomenclature: HCN2

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 HCN2 in GtoImmuPdb

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 889 19p13.3 HCN2 hyperpolarization activated cyclic nucleotide gated potassium and sodium channel 2 34
Mouse 6 1 863 10 C1 Hcn2 hyperpolarization-activated, cyclic nucleotide-gated K+ 2 33,50
Rat 6 1 863 7q11 Hcn2 hyperpolarization activated cyclic nucleotide gated potassium and sodium channel 2 39
Previous and Unofficial Names
BCNG2 | HAC1 | hyperpolarization activated cyclic nucleotide gated potassium channel 2 | hyperpolarization-activated, cyclic nucleotide-gated K+ 2 | hyperpolarization-activated
Database Links
CATH/Gene3D
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
HCN1 42,57
HCN4 42
Auxiliary Subunits
Name References
KCNE2 2,47,64
Trip8b 1,5,29
Other Associated Proteins
Name References
KCR1 38
Tamalin, S-SCAM and Mint2 26
C-terminal Src kinase 67
K2P9.1 36
Protein kinase G (PKG) 2 19
Ion Selectivity and Conductance
Species:  None
Rank order:  K+ > Na+ > Ca2+ [1.5 - 35.0 pS]
References:  10,32,37,65
Voltage Dependence
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -130.0 – -136.0 (median: -132.0) - 9,59 Xenopus laevis oocyte Mouse
Inactivation  - -
Comments  Inside-out patch.
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -95.0 – -103.0 (median: -100.0) 200.0 – 500.0 25,32,53 HEK 293 cells. Human
Inactivation  - -
Comments  V0.5 and τ-values are strongly influenced by experimental parameters such as temperature, pH and pulse protocol.
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -78.0 - 9 Xenopus laevis oocyte Mouse
Inactivation  - -
Comments  Whole-cell patch clamp.
Activators (Human)
cyclic AMP > cyclic GMP

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 6.3 pKi - -40.0 33
pKi 6.3 [33]
Holding voltage: -40.0 mV
cyclic GMP Mm Agonist 5.2 pKi - -40.0 33
pKi 5.2 [33]
Holding voltage: -40.0 mV
PIP2 Mm - 5.0 pEC50 - -35.0 46
pEC50 5.0 (EC50 1.09x10-5 M) [46]
Holding voltage: -35.0 mV
cyclic CMP Mm - 4.5 pEC50 - -40.0 68
pEC50 4.5 (EC50 3x10-5 M) [68]
Holding voltage: -40.0 mV
Activator Comments
cAMP and cGMP shift V0.5 by +10 to +20 mV [33-34,49,59].
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
cilobradine Hs Antagonist 6.0 pIC50 - -40.0 54
pIC50 6.0 [54]
Holding voltage: -40.0 mV
zatebradine Hs Antagonist 5.7 pIC50 - -40.0 54
pIC50 5.7 [54]
Holding voltage: -40.0 mV
ivabradine Mm Antagonist 5.6 pIC50 - - 54
pIC50 5.6 (IC50 2.29x10-6 M) [54]
clonidine Mm Antagonist 5.1 pIC50 - -40.0 27
pIC50 5.1 [27]
Holding voltage: -40.0 mV
ZD7288 Hs Antagonist 4.4 pIC50 - - 53
pIC50 4.4 (IC50 4.1x10-5 M) [53]
Cs+ Hs Antagonist 3.7 pIC50 - -40.0 53
pIC50 3.7 (IC50 2.06x10-7 M) [53]
Holding voltage: -40.0 mV
Mg2+ Mm - 3.2 pIC50 - 50.0 58
pIC50 3.2 [58]
Holding voltage: 50.0 mV
View species-specific channel blocker tables
Channel Blocker Comments
Propofol inhibits and slows activation of the mouse HCN2 channel at clinically relevant concentrations [4].
Tissue Distribution
Heart.
Species:  Human
Technique:  Northern Blot
References:  34
Brain.
Species:  Human
Technique:  Northern Blot
References:  34
Brain.
Species:  Mouse
Technique:  In situ hybridisation
References:  40
Heart.
Species:  Mouse
Technique:  In situ hybridisation, RT-PCR and immunohistochemistry.
References:  21,41
Gastrointestinal (GI) tract
Species:  Mouse
Technique:  Immunohistochemistry
References:  62
Pancreatic beta cells.
Species:  Mouse
Technique:  Voltage-clamp.
References:  15,66
Cochlear and vestibular hair cells.
Species:  Mouse
Technique:  Immunohistochemistry and patch clamp electrophysiology.
References:  22-23,48
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:  28
Pancreatic beta cells.
Species:  Rat
Technique:  Voltage-clamp.
References:  15,66
Brain.
Species:  Rat
Technique:  Immunohistochemistry
References:  44
Heart.
Species:  Rat
Technique:  RNAse protection assay.
References:  52
Urinary bladder.
Species:  Rat
Technique:  RT-PCR and Western blot.
References:  20
Retina (bipolar cell bodies, type 5 bipolar cells).
Species:  Rat
Technique:  Immunohistochemistry
References:  43
Physiological Functions
Modulation of firing mode of thalamic neurons.
Species:  Mouse
Tissue:  Brain.
References:  31
Determination of resting membrane potential.
Species:  Mouse
Tissue:  Neurones, cardiac pacemaker cells.
References:  31
Involvement in retinal photoresponses to dim light.
Species:  Mouse
Tissue:  Retina
References:  11
Ammonium transport in the distal nephron.
Species:  Rat
Tissue:  Kidney
References:  6
Involvement in inflammatory and neuropathic pain.
Species:  Mouse
Tissue:  Brain and peripheral nervous system.
References:  14,16-17,45,60
Modulation of synaptic plasticity in the hippocampal direct perforant path.
Species:  Mouse
Tissue:  Brain
References:  35
Modulation of L-type calcium channel inactivation.
Species:  Rat
Tissue:  Heart
References:  30
Constraint of excitatory synaptic integration in reticular thalamic nucleus (RTN) neurons.
Species:  Mouse
Tissue:  Brain
References:  63
Physiological Consequences of Altering Gene Expression
The HCN2 knockout mouse has absence epilepsy, ataxia and sinus dysrhythmia.
Species:  Mouse
Tissue:  Brain and heart.
Technique:  Knockout
References:  31
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Hcn2tm1Ldw Hcn2tm1Ldw/Hcn2tm1Ldw
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1298210  MP:0003412 abnormal afterhyperpolarization PMID: 12514127 
Hcn2ap Hcn2ap/Hcn2ap
DW/Pas-Hcn2
MGI:1298210  MP:0002572 abnormal emotion/affect behavior PMID: 19150498 
Hcn2ap Hcn2ap/Hcn2ap
DW/Pas-Hcn2
MGI:1298210  MP:0001406 abnormal gait PMID: 19150498 
Hcn2ap Hcn2ap/Hcn2ap
DW/Pas-Hcn2
MGI:1298210  MP:0003312 abnormal locomotor coordination PMID: 19150498 
Hcn2tm1Ldw Hcn2tm1Ldw/Hcn2tm1Ldw
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1298210  MP:0002272 abnormal nervous system electrophysiology PMID: 12514127 
Hcn2ap Hcn2ap/Hcn2ap
DW/Pas-Hcn2
MGI:1298210  MP:0001504 abnormal posture PMID: 19150498 
Hcn2tm1Ldw Hcn2tm1Ldw/Hcn2tm1Ldw
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1298210  MP:0006142 abnormal sinoatrial node conduction PMID: 12514127 
Hcn2tm1Ldw|Hcn2tm2Ldw|Myl7+|Myl7tm1(cre)Krc Hcn2tm1Ldw/Hcn2tm2Ldw,Myl7tm1(cre)Krc/Myl7+
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:107495  MGI:1298210  MP:0006142 abnormal sinoatrial node conduction PMID: 12514127 
Hcn2ap Hcn2ap/Hcn2ap
DW/Pas-Hcn2
MGI:1298210  MP:0008840 abnormal spike wave discharge PMID: 19150498 
Hcn2+|Hcn2ap Hcn2ap/Hcn2+
DW/Pas-Hcn2
MGI:1298210  MP:0008840 abnormal spike wave discharge PMID: 19150498 
Hcn2tm1Ldw Hcn2tm1Ldw/Hcn2tm1Ldw
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1298210  MP:0003470 abnormal summary potential PMID: 12514127 
Hcn2tm1Ldw Hcn2tm1Ldw/Hcn2tm1Ldw
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1298210  MP:0003216 absence seizures PMID: 12514127 
Hcn2ap Hcn2ap/Hcn2ap
DW/Pas-Hcn2
MGI:1298210  MP:0003216 absence seizures PMID: 19150498 
Hcn2+|Hcn2ap Hcn2ap/Hcn2+
DW/Pas-Hcn2
MGI:1298210  MP:0003216 absence seizures PMID: 19150498 
Hcn2ap Hcn2ap/Hcn2ap
DW/Pas-Hcn2
MGI:1298210  MP:0001393 ataxia PMID: 19150498 
Hcn2ap Hcn2ap/Hcn2ap
DW/Pas-Hcn2
MGI:1298210  MP:0001258 decreased body length PMID: 19150498 
Hcn2tm1Ldw Hcn2tm1Ldw/Hcn2tm1Ldw
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1298210  MP:0001262 decreased body weight PMID: 12514127 
Hcn2ap Hcn2ap/Hcn2ap
DW/Pas-Hcn2
MGI:1298210  MP:0001262 decreased body weight PMID: 19150498 
Hcn2tm1Ldw Hcn2tm1Ldw/Hcn2tm1Ldw
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1298210  MP:0003488 decreased channel response intensity PMID: 12514127 
Hcn2tm1Ldw Hcn2tm1Ldw/Hcn2tm1Ldw
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1298210  MP:0001402 hypoactivity PMID: 12514127 
Hcn2ap Hcn2ap/Hcn2ap
DW/Pas-Hcn2
MGI:1298210  MP:0001402 hypoactivity PMID: 19150498 
Hcn2ap Hcn2ap/Hcn2ap
DW/Pas-Hcn2
MGI:1298210  MP:0001525 impaired balance PMID: 19150498 
Hcn2ap Hcn2ap/Hcn2ap
DW/Pas-Hcn2
MGI:1298210  MP:0001522 impaired swimming PMID: 19150498 
Hcn2ap Hcn2ap/Hcn2ap
DW/Pas-Hcn2
MGI:1298210  MP:0001409 increased stereotypic behavior PMID: 19150498 
Hcn2+|Hcn2ap Hcn2ap/Hcn2+
DW/Pas-Hcn2
MGI:1298210  MP:0002906 increased susceptibility to pharmacologically induced seizures PMID: 19150498 
Hcn2tm1Ldw Hcn2tm1Ldw/Hcn2tm1Ldw
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1298210  MP:0001636 irregular heartbeat PMID: 12514127 
Hcn2tm1Ldw|Hcn2tm2Ldw|Myl7+|Myl7tm1(cre)Krc Hcn2tm1Ldw/Hcn2tm2Ldw,Myl7tm1(cre)Krc/Myl7+
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:107495  MGI:1298210  MP:0001636 irregular heartbeat PMID: 12514127 
Hcn2ap Hcn2ap/Hcn2ap
DW/Pas-Hcn2
MGI:1298210  MP:0002083 premature death PMID: 19150498 
Hcn2ap Hcn2ap/Hcn2ap
DW/Pas-Hcn2
MGI:1298210  MP:0003997 tonic-clonic seizures PMID: 19150498 
Hcn2tm1Ldw Hcn2tm1Ldw/Hcn2tm1Ldw
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1298210  MP:0000745 tremors PMID: 12514127 
Hcn2ap Hcn2ap/Hcn2ap
DW/Pas-Hcn2
MGI:1298210  MP:0000745 tremors PMID: 19150498 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Febrile seizures, familial, 1; FEB1
OMIM: 121210
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
In-frame deletion Human P719_P721del c.2156-2164delCGCCGCCGC The triple proline deletion (delPPP) in HCN2 is associated with febrile seizure. 12
Disease:  Generalized epilepsy with febrile seizures plus, type 1; GEFSP1
Synonyms: Generalized epilepsy with febrile seizures-plus [Disease Ontology: DOID:0060170] [Orphanet: ORPHA36387]
Disease Ontology: DOID:0060170
OMIM: 604233
Orphanet: ORPHA36387
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human E515K In patients with IGE the mutation E515K in HCN2 causes elevated neuronal activity. 13
Missense Human R527Q In patients with IGE the mutation R527Q results in decreased slope of the conductance-voltage relation. 55
Disease:  Sudden unexpected death in epilepsy
Synonyms: SUDEP
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human F738C The F738C variant in HCN2 affects the highly conserved residues in the carboxyl-cytoplasmic tail region. 56
Missense Human P802S The P802S variant in HCN2 affects the highly conserved residues in the carboxyl-cytoplasmic tail region. 56
Gene Expression and Pathophysiology
Upregulation of HCN2 mRNA levels in hypertrophied myocytes from rat left ventricle.
Tissue or cell type:  Cardiac myocytes.
Pathophysiology:  Cardiac hypertrophy.
Species:  Rat
Technique: 
References:  18
Expression in cardiac ventricles of hypertrophied aged rats.
Tissue or cell type:  Ventricle.
Pathophysiology:  Induction of arrhythmia in heart failure.
Species:  Rat
Technique: 
References:  7
Elevated HCN2 expression in SP-mediated spinal pain processing.
Tissue or cell type:  Spinal dorsal horn.
Pathophysiology:  Inflammatory pain.
Species:  Rat
Technique:  Unilateral injection of complete Freund's adjuvant (CFA).
References:  45
Downregulation of HCN2 in globus pallidus in mouse model of Parkinson’s disease.
Tissue or cell type:  Globus pallidus.
Pathophysiology:  Parkinson’s disease.
Species:  Mouse
Technique: 
References:  8
Increase in HCN2 expression in the thalamocortical neurons of epileptic rats (WAG/Rij).
Tissue or cell type:  Thalamocortical neuons.
Pathophysiology:  Absence epilepsy.
Species:  Rat
Technique: 
References:  3,24
Increased HCN2 expression in the mesocorticolimbic system via cocaine sensitization.
Tissue or cell type:  Ventral tegmental area, prefrontal cortex, nucleus accumbens, and hippocampus.
Pathophysiology:  Drug abuse.
Species:  Rat
Technique:  Western blot.
References:  51
Increased HCN2 expression in ventricular cells in heart after acute myocardial infarction (AMI).
Tissue or cell type:  Ventricle.
Pathophysiology: 
Species:  Rat
Technique:  RT-PCR, immunohistochemistry and Western blot.
References:  61

References

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1. Bankston JR, Camp SS, DiMaio F, Lewis AS, Chetkovich DM, Zagotta WN. (2012) Structure and stoichiometry of an accessory subunit TRIP8b interaction with hyperpolarization-activated cyclic nucleotide-gated channels. Proc. Natl. Acad. Sci. U.S.A., 109 (20): 7899-904. [PMID:22550182]

2. Brandt MC, Endres-Becker J, Zagidullin N, Motloch LJ, Er F, Rottlaender D, Michels G, Herzig S, Hoppe UC. (2009) Effects of KCNE2 on HCN isoforms: distinct modulation of membrane expression and single channel properties. Am. J. Physiol. Heart Circ. Physiol., 297 (1): H355-63. [PMID:19429827]

3. 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]

4. 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]

5. Cao-Ehlker X, Zong X, Hammelmann V, Gruner C, Fenske S, Michalakis S, Wahl-Schott C, Biel M. (2013) Up-regulation of hyperpolarization-activated cyclic nucleotide-gated channel 3 (HCN3) by specific interaction with K+ channel tetramerization domain-containing protein 3 (KCTD3). J. Biol. Chem., 288 (11): 7580-9. [PMID:23382386]

6. Carrisoza-Gaytán R, Rangel C, Salvador C, Saldaña-Meyer R, Escalona C, Satlin LM, Liu W, Zavilowitz B, Trujillo J, Bobadilla NA et al.. (2011) The hyperpolarization-activated cyclic nucleotide-gated HCN2 channel transports ammonium in the distal nephron. Kidney Int., 80 (8): 832-40. [PMID:21796099]

7. Cerbai E, Mugelli A. (2006) I(f) in non-pacemaker cells: role and pharmacological implications. Pharmacol. Res., 53 (5): 416-23. [PMID:16713285]

8. Chan CS, Glajch KE, Gertler TS, Guzman JN, Mercer JN, Lewis AS, Goldberg AB, Tkatch T, Shigemoto R, Fleming SM et al.. (2011) HCN channelopathy in external globus pallidus neurons in models of Parkinson's disease. Nat. Neurosci., 14 (1): 85-92. [PMID:21076425]

9. 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]

10. Dekker JP, Yellen G. (2006) Cooperative gating between single HCN pacemaker channels. J. Gen. Physiol., 128 (5): 561-7. [PMID:17043149]

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. Dibbens LM, Reid CA, Hodgson B, Thomas EA, Phillips AM, Gazina E, Cromer BA, Clarke AL, Baram TZ, Scheffer IE et al.. (2010) Augmented currents of an HCN2 variant in patients with febrile seizure syndromes. Ann. Neurol., 67 (4): 542-6. [PMID:20437590]

13. DiFrancesco JC, Barbuti A, Milanesi R, Coco S, Bucchi A, Bottelli G, Ferrarese C, Franceschetti S, Terragni B, Baruscotti M et al.. (2011) Recessive loss-of-function mutation in the pacemaker HCN2 channel causing increased neuronal excitability in a patient with idiopathic generalized epilepsy. J. Neurosci., 31 (48): 17327-37. [PMID:22131395]

14. 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]

15. 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]

16. Emery EC, Young GT, Berrocoso EM, Chen L, McNaughton PA. (2011) HCN2 ion channels play a central role in inflammatory and neuropathic pain. Science, 333 (6048): 1462-6. [PMID:21903816]

17. Emery EC, Young GT, McNaughton PA. (2012) HCN2 ion channels: an emerging role as the pacemakers of pain. Trends Pharmacol. Sci., 33 (8): 456-63. [PMID:22613784]

18. Fernández-Velasco M, Goren N, Benito G, Blanco-Rivero J, Boscá L, Delgado C. (2003) Regional distribution of hyperpolarization-activated current (If) and hyperpolarization-activated cyclic nucleotide-gated channel mRNA expression in ventricular cells from control and hypertrophied rat hearts. J. Physiol. (Lond.), 553 (Pt 2): 395-405. [PMID:14514868]

19. Hammelmann V, Zong X, Hofmann F, Michalakis S, Biel M. (2011) The cGMP-dependent protein kinase II Is an inhibitory modulator of the hyperpolarization-activated HCN2 channel. PLoS ONE, 6 (2): e17078. [PMID:21347269]

20. 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]

21. Herrmann S, Layh B, Ludwig A. (2011) Novel insights into the distribution of cardiac HCN channels: an expression study in the mouse heart. J. Mol. Cell. Cardiol., 51 (6): 997-1006. [PMID:21945247]

22. 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]

23. 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]

24. Kanyshkova T, Meuth P, Bista P, Liu Z, Ehling P, Caputi L, Doengi M, Chetkovich DM, Pape HC, Budde T. (2012) Differential regulation of HCN channel isoform expression in thalamic neurons of epileptic and non-epileptic rat strains. Neurobiol. Dis., 45 (1): 450-61. [PMID:21945537]

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

26. Kimura K, Kitano J, Nakajima Y, Nakanishi S. (2004) Hyperpolarization-activated, cyclic nucleotide-gated HCN2 cation channel forms a protein assembly with multiple neuronal scaffold proteins in distinct modes of protein-protein interaction. Genes Cells, 9 (7): 631-40. [PMID:15265006]

27. 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]

28. 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]

29. 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]

30. Lin YC, Huang J, Zhang Q, Hollander JM, Frisbee JC, Martin KH, Nestor C, Goodman R, Yu HG. (2010) Inactivation of L-type calcium channel modulated by HCN2 channel. Am. J. Physiol., Cell Physiol., 298 (5): C1029-37. [PMID:20164379]

31. Ludwig A, Budde T, Stieber J, Moosmang S, Wahl C, Holthoff K, Langebartels A, Wotjak C, Munsch T, Zong X, Feil S, Feil R, Lancel M, Chien KR, Konnerth A, Pape HC, Biel M, Hofmann F. (2003) Absence epilepsy and sinus dysrhythmia in mice lacking the pacemaker channel HCN2. EMBO J., 22 (2): 216-24. [PMID:12514127]

32. 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]

33. 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]

34. Ludwig A, Zong X, Stieber J, Hullin R, Hofmann F, Biel M. (1999) Two pacemaker channels from human heart with profoundly different activation kinetics. EMBO J., 18 (9): 2323-9. [PMID:10228147]

35. Matt L, Michalakis S, Hofmann F, Hammelmann V, Ludwig A, Biel M, Kleppisch T. (2011) HCN2 channels in local inhibitory interneurons constrain LTP in the hippocampal direct perforant path. Cell. Mol. Life Sci., 68 (1): 125-37. [PMID:20623157]

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Verena Hammelmann, Martin Biel.
Cyclic nucleotide-regulated channels: HCN2. Last modified on 10/03/2017. Accessed on 15/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=401.