Gene Symbol: HCN2
Description: hyperpolarization activated cyclic nucleotide gated potassium and sodium channel 2
Alias: BCNG-2, BCNG2, HAC-1, potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2, brain cyclic nucleotide-gated channel 2, hyperpolarization activated cyclic nucleotide gated potassium channel 2
Species: human
Products:     HCN2

Top Publications

  1. Santoro B, Liu D, Yao H, Bartsch D, Kandel E, Siegelbaum S, et al. Identification of a gene encoding a hyperpolarization-activated pacemaker channel of brain. Cell. 1998;93:717-29 pubmed
  2. Ulens C, Tytgat J. Functional heteromerization of HCN1 and HCN2 pacemaker channels. J Biol Chem. 2001;276:6069-72 pubmed
    ..In this study, we have provided evidence for functional heteromerization of HCN1 and HCN2 channels using a concatenated cDNA construct encoding two connected subunits...
  3. Proenza C, Tran N, Angoli D, Zahynacz K, Balcar P, Accili E. Different roles for the cyclic nucleotide binding domain and amino terminus in assembly and expression of hyperpolarization-activated, cyclic nucleotide-gated channels. J Biol Chem. 2002;277:29634-42 pubmed
    ..We show here that the N termini of the HCN1 and HCN2 isoforms interacted and were essential for expression of functional homo- or heteromeric channels on the plasma ..
  4. Michels G, Er F, Khan I, Südkamp M, Herzig S, Hoppe U. Single-channel properties support a potential contribution of hyperpolarization-activated cyclic nucleotide-gated channels and If to cardiac arrhythmias. Circulation. 2005;111:399-404 pubmed
    ..Single-channel properties of cells cotransfected with HCN2 and HCN4 were distinct from cells expressing HCN2 or HCN4 alone, demonstrating that different HCN isoforms can ..
  5. Dibbens L, Reid C, Hodgson B, Thomas E, Phillips A, Gazina E, et al. Augmented currents of an HCN2 variant in patients with febrile seizure syndromes. Ann Neurol. 2010;67:542-6 pubmed publisher
    ..4% carried a common triple proline deletion (delPPP) in HCN2 that was seen in only 0.2% of blood bank controls...
  6. Much B, Wahl Schott C, Zong X, Schneider A, Baumann L, Moosmang S, et al. Role of subunit heteromerization and N-linked glycosylation in the formation of functional hyperpolarization-activated cyclic nucleotide-gated channels. J Biol Chem. 2003;278:43781-6 pubmed
    ..We also identified HCN1/HCN2 heteromers in mouse brain indicating that heteromeric channels exist in vivo...
  7. Biel M, Wahl Schott C, Michalakis S, Zong X. Hyperpolarization-activated cation channels: from genes to function. Physiol Rev. 2009;89:847-85 pubmed publisher
    ..Finally, we provide an overview of the impact of HCN channels on the pathogenesis of several diseases and discuss recent attempts to establish HCN channels as drug targets. ..
  8. DiFrancesco J, Barbuti A, Milanesi R, Coco S, Bucchi A, Bottelli G, et al. Recessive loss-of-function mutation in the pacemaker HCN2 channel causing increased neuronal excitability in a patient with idiopathic generalized epilepsy. J Neurosci. 2011;31:17327-37 pubmed publisher
    ..By screening families with epilepsy for mutations in Hcn1 and Hcn2 genes, we found a recessive loss-of-function point mutation in the gene coding for the HCN2 channel in a patient ..
  9. Idikuda V, Gao W, Su Z, Liu Q, Zhou L. cAMP binds to closed, inactivated, and open sea urchin HCN channels in a state-dependent manner. J Gen Physiol. 2019;151:200-213 pubmed publisher
    ..Previous studies of mouse HCN2 (mHCN2) channels have shown that cAMP binds preferentially to and stabilizes these channels in the open state-a ..

More Information

Publications130 found, 100 shown here

  1. Zuo G, Ren X, Ge Q, Luo J, Ye P, Wang F, et al. Activation of the PP2A catalytic subunit by ivabradine attenuates the development of diabetic cardiomyopathy. J Mol Cell Cardiol. 2019;: pubmed publisher
    ..treatment significantly inhibited left ventricular hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) and HCN4 (major components of the If current), activated PP2Ac, and attenuated NF-κB signaling ..
  2. Zhang M, Guo H, Ma Y, Xu F, Bai F, Liang S, et al. Acupoint Sensitization is Associated with Increased Excitability and Hyperpolarization-Activated Current (Ih) in C- But Not Aδ-Type Neurons. Neuroscience. 2019;404:499-509 pubmed publisher
    ..HCN channel subtype 2 (HCN2) expression levels significantly increased after acupoint sensitization...
  3. Richards N, Dilley A. Contribution of hyperpolarization-activated channels to heat hypersensitivity and ongoing activity in the neuritis model. Neuroscience. 2015;284:87-98 pubmed publisher
    ..Immunohistochemical examination of the HCN2 channel subtype within the L5 dorsal root ganglia revealed an increase in expression in neuronal cell bodies of all ..
  4. Gunther A, Luczak V, Gruteser N, Abel T, Baumann A. HCN4 knockdown in dorsal hippocampus promotes anxiety-like behavior in mice. Genes Brain Behav. 2019;18:e12550 pubmed publisher
    ..Disruption of the Ih current by knockout of HCN1, HCN2 or tetratricopeptide repeat-containing Rab8b-interacting protein has been shown to affect physiological processes ..
  5. Santos Vera B, Vaquer Alicea A, Maria Rios C, Montiel Ramos A, Ramos Cardona A, Vázquez Torres R, et al. Protein and surface expression of HCN2 and HCN4 subunits in mesocorticolimbic areas after cocaine sensitization. Neurochem Int. 2019;125:91-98 pubmed publisher
    ..Previously, we reported that cocaine-induced behavioral sensitization increases HCN2 protein expression in all MCL areas with the Ventral Tegmental Area (VTA) showing the most significant increase...
  6. Qiu J, Rivera H, Bosch M, Padilla S, Stincic T, Palmiter R, et al. Estrogenic-dependent glutamatergic neurotransmission from kisspeptin neurons governs feeding circuits in females. elife. 2018;7: pubmed publisher
    ..we show that E2 augmented the excitability of Kiss1ARH neurons by amplifying Cacna1g, Hcn1 and Hcn2 mRNA expression and T-type calcium and h-currents...
  7. Ramirez D, Zúñiga R, Concha G, Zúñiga L. HCN Channels: New Therapeutic Targets for Pain Treatment. Molecules. 2018;23: pubmed publisher
    ..The HCN currents (Ih) mediated by HCN1 and HCN2 drive the repetitive firing in nociceptive neurons...
  8. Cheng J, Umschweif G, Leung J, Sagi Y, Greengard P. HCN2 Channels in Cholinergic Interneurons of Nucleus Accumbens Shell Regulate Depressive Behaviors. Neuron. 2019;101:662-672.e5 pubmed publisher
    ..we found that the expression and function of the hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) are decreased in ChIs of NAc shell in depressed mice...
  9. Pham T, Nguyen T, Van Bui A, Nguyen M, Van Pham P. Fetal heart extract facilitates the differentiation of human umbilical cord blood-derived mesenchymal stem cells into heart muscle precursor cells. Cytotechnology. 2016;68:645-58 pubmed publisher
    ..5, Gata 4, Mef2c, HCN2, hBNP, α-Ca, cTnT, Desmin, and β-MHC on day 27 in the Aza group and on day 18 in the Aza + HE group...
  10. Djouhri L, Al Otaibi M, Kahlat K, Smith T, Sathish J, Weng X. Persistent hindlimb inflammation induces changes in activation properties of hyperpolarization-activated current (Ih) in rat C-fiber nociceptors in vivo. Neuroscience. 2015;301:121-33 pubmed publisher
    ..is associated with increased expression of hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) protein and hyperpolarization-activated current (Ih) in C-nociceptors...
  11. Arakawa K, Kaku R, Kurita M, Matsuoka Y, Morimatsu H. Prolonged-duration pulsed radiofrequency is associated with increased neuronal damage without further antiallodynic effects in neuropathic pain model rats. J Pain Res. 2018;11:2645-2651 pubmed publisher
    ..01), but the expression of HCN1 and HCN2 channels did not differ significantly between the three groups...
  12. O Donnell A, Coyle D, Puri P. Decreased expression of hyperpolarisation-activated cyclic nucleotide-gated channel 3 in Hirschsprung's disease. World J Gastroenterol. 2015;21:5635-40 pubmed publisher
    ..We investigated HCN1, HCN2, HCN3 and HCN4 protein expression in pull-through specimens from patients with Hirschsprung's disease (HSCR, n = 10)..
  13. Otte M, Schweinitz A, Bonus M, Enke U, Schumann C, Gohlke H, et al. Hydrophobic alkyl chains substituted to the 8-position of cyclic nucleotides enhance activation of CNG and HCN channels by an intricate enthalpy - entropy compensation. Sci Rep. 2018;8:14960 pubmed publisher
    ..The compounds were tested in homotetrameric CNGA2, heterotetrameric CNGA2:CNGA4:CNGB1b and homotetrameric HCN2 channels...
  14. Chen S, Xu Y, Liang Y, Cao Y, Lv J, Pang J, et al. Identification and characterization of a series of novel HCN channel inhibitors. Acta Pharmacol Sin. 2018;: pubmed publisher
    ..9 ± 1.2 µM at - 120 mV on HCN2 channel expressed in COS7 cells...
  15. Chen K, Zuo D, Liu Z, Chen H. Kir2.1 channels set two levels of resting membrane potential with inward rectification. Pflugers Arch. 2018;470:599-611 pubmed publisher
    ..Under hypokalemic conditions, Kir2.1 currents counterbalance HCN2 or HCN4 cation currents in CHO cells that heterologously express both channels, generating N-shaped current-voltage ..
  16. Xiang X, Zhou Y, Sun H, Tan S, Lu Z, Huang L, et al. Ivabradine abrogates TNF-α-induced degradation of articular cartilage matrix. Int Immunopharmacol. 2019;66:347-353 pubmed publisher
    ..Knockdown of HCN2 enhanced the protective effects of ivabradine against TNF-α- induced degradation of both type II collagen and ..
  17. Gossner A, Hopkins J. Transcriptome analysis of CNS immediately before and after the detection of PrP(Sc) in SSBP/1 sheep scrapie. Vet Microbiol. 2014;173:201-7 pubmed publisher
    ..Several neurological receptors were significantly increased at D75 (e.g. CHRNA6, GRM1, HCN2), which might be clues to the molecular basis of psychiatric changes associated with TSEs...
  18. Deberg H, Bankston J, Rosenbaum J, Brzovic P, Zagotta W, Stoll S. Structural mechanism for the regulation of HCN ion channels by the accessory protein TRIP8b. Structure. 2015;23:734-44 pubmed publisher
    ..resonance (EPR) to show that TRIP8b binds to the apo state of the cyclic nucleotide binding domain (CNBD) of HCN2 channels without changing the overall domain structure...
  19. Smith T, Al Otaibi M, Sathish J, Djouhri L. Increased expression of HCN2 channel protein in L4 dorsal root ganglion neurons following axotomy of L5- and inflammation of L4-spinal nerves in rats. Neuroscience. 2015;295:90-102 pubmed publisher
    ..We found 7days after mSNA: (1) a significant increase in HCN2-immunoreactivity in small (<30μm) DRG neurons (predominantly IB4-negative neurons), and in the proportion of ..
  20. Yang C, Zhang J, Chen L, Ge S, Wang J, Yan Z, et al. Decreased HCN2 expression in STN contributes to abnormal high-voltage spindles in the cortex and globus pallidus of freely moving rats. Brain Res. 2015;1618:17-28 pubmed publisher
    ..how dopamine D2-like receptors regulate HVSs and the role of hyperpolarization-activated cyclic nucleotide-gated2 (HCN2) in HVSs regulation...
  21. Yu H, Xia S, Zha C, Deng S, Du J, She Q. Spironolactone Regulates HCN Protein Expression Through Micro-RNA-1 in Rats With Myocardial Infarction. J Cardiovasc Pharmacol. 2015;65:587-92 pubmed publisher
    ..The border zone of the myocardial infarct was collected from each rat at 1 week after MI. HCN2 and HCN4 protein and messenger RNA (mRNA) level were measured in addition to miRNA-1 levels...
  22. Collauto A, Deberg H, Kaufmann R, Zagotta W, Stoll S, Goldfarb D. Rates and equilibrium constants of the ligand-induced conformational transition of an HCN ion channel protein domain determined by DEER spectroscopy. Phys Chem Chem Phys. 2017;19:15324-15334 pubmed publisher
    ..transition of the nitroxide labeled, isolated carboxy-terminal cyclic-nucleotide binding domain (CNBD) of the HCN2 ion channel upon binding of the ligand 3',5'-cyclic adenosine monophosphate (cAMP)...
  23. Song F, Zhao J, Hua F, Nian L, Zhou X, Yang Q, et al. Proliferation of rat cardiac stem cells is induced by 2, 3, 5, 4'-tetrahydroxystilbene-2-O-β-D-glucoside in vitro. Life Sci. 2015;132:68-76 pubmed publisher
    ..growth factor (VEGF), T-box transcription factor (Tbx5), hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2), hyperpolarization-activated cyclic nucleotide gated 4 (HCN4), alpha myosin heavy chain (αMHC), and beta myosin ..
  24. Xu Y, Chen S, Cao Y, Zhou P, Chen Z, Cheng K. Discovery of novel small molecule TLR4 inhibitors as potent anti-inflammatory agents. Eur J Med Chem. 2018;154:253-266 pubmed publisher
    ..More interestingly, 8a shows higher affinity to hyperpolarization-activated cyclic nucleotide-gated 4 (HCN4) over HCN2, which probably indicates the new application of TLR4 inhibitor 8a in heart failure, coronary heart disease, and ..
  25. Zhou S, Kai H, Zha Z, Fang Z, Wang D, Du L, et al. Subcellular distribution and chemical forms of thorium in Brassica juncea var. foliosa. J Environ Radioact. 2016;157:60-6 pubmed publisher
    ..This suggested that Th compartmentation in cytosol and integration with phosphate or proteins in cell wall might be responsible for the tolerance of B. juncea var. foliosa to the stress of Th. ..
  26. Zhao Z, Zhang K, Liu X, Yan H, Ma X, Zhang S, et al. Involvement of HCN Channel in Muscarinic Inhibitory Action on Tonic Firing of Dorsolateral Striatal Cholinergic Interneurons. Front Cell Neurosci. 2016;10:71 pubmed publisher
    ..Among them, M2 receptors and HCN2 channels were the most dominant ones and expressed in every single studied cholinergic interneuron (ChI)...
  27. Maddirevula S, Alzahrani F, Al Owain M, Al Muhaizea M, Kayyali H, Alhashem A, et al. Autozygome and high throughput confirmation of disease genes candidacy. Genet Med. 2019;21:736-742 pubmed publisher
    ..deleterious variants in 18 published candidate genes (ABCA2, ARL6IP1, ATP8A2, CDK9, CNKSR1, DGAT1, DMXL2, GEMIN4, HCN2, HCRT, MYO9A, PARS2, PLOD3, PREPL, SCLT1, STX3, TXNRD2, WIPI2) although the associated phenotypes are sufficiently ..
  28. Li Y, Hong Y, Zhang Y, Zhou X, Ji Y, Li H, et al. Association between reversal in the expression of hyperpolarization-activated cyclic nucleotide-gated (HCN) channel and age-related atrial fibrillation. Med Sci Monit. 2014;20:2292-7 pubmed publisher
    ..Expression levels of HCN2 and HCN4 channel mRNAs and proteins were measured in the sinoatrial node, atrium, and pulmonary veins by real-time ..
  29. Spinelli V, Sartiani L, Mugelli A, Romanelli M, Cerbai E. HCN channels: pathophysiological, developmental and pharmacological insights into their function in cellular excitability. Can J Physiol Pharmacol. 2018;: pubmed publisher
    ..of intense study, including the synthesis and characterization of new compounds able to block preferentially HCN1, HCN2 or HCN4 isoforms...
  30. López González Z, Ayala Aguilera C, Martinez Morales F, Galicia Cruz O, Salvador Hernández C, Pedraza Chaverri J, et al. Immunolocalization of hyperpolarization-activated cationic HCN1 and HCN3 channels in the rat nephron: regulation of HCN3 by potassium diets. Histochem Cell Biol. 2016;145:25-40 pubmed publisher
    ..HCN channels are found in excitable and non-excitable tissues in mammals. We have previously shown that HCN2 may transport ammonium (NH4 (+)), besides sodium (Na(+)), in the rat distal nephron...
  31. David F, Carçak N, Furdan S, Onat F, Gould T, Mészáros A, et al. Suppression of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel Function in Thalamocortical Neurons Prevents Genetically Determined and Pharmacologically Induced Absence Seizures. J Neurosci. 2018;38:6615-6627 pubmed publisher
    ..These results provide the first evidence that block of TC neuron HCN channels prevents absence seizures. ..
  32. Huff L, Sackett D, Poruchynsky M, Fojo T. Microtubule-disrupting chemotherapeutics result in enhanced proteasome-mediated degradation and disappearance of tubulin in neural cells. Cancer Res. 2010;70:5870-9 pubmed publisher
    ..Studies showed that microtubule-depolymerizing agents (MDA) not only disassembled microtubules in neural HCN2 cells but also led to rapid disappearance of tubulin, and that this was specific for MDAs...
  33. Schweikart K, Guo L, Shuler Z, Abrams R, Chiao E, Kolaja K, et al. The effects of jaspamide on human cardiomyocyte function and cardiac ion channel activity. Toxicol In Vitro. 2013;27:745-51 pubmed publisher
    ..5 activity by 98.5%. Jaspamide also inhibited other channels including Cav1.2, Cav3.2, and HCN2; however, the Kv11.1 (hERG) channel was minimally affected...
  34. Oshita K, Itoh M, Hirashima S, Kuwabara Y, Ishihara K, Kuwahara K, et al. Ectopic automaticity induced in ventricular myocytes by transgenic overexpression of HCN2. J Mol Cell Cardiol. 2015;80:81-9 pubmed publisher
    ..To test this hypothesis, we generated and analyzed transgenic mice overexpressing HCN2 specifically in their hearts (HCN2-Tg)...
  35. Seo H, Seol M, Lee K. Differential expression of hyperpolarization-activated cyclic nucleotide-gated channel subunits during hippocampal development in the mouse. Mol Brain. 2015;8:13 pubmed publisher
    ..Here we examined the developmental expression of the brain-enriched HCN1, HCN2, and HCN4 isoforms of HCN channels in mouse hippocampus from embryonic to postnatal stages...
  36. Wen Y, Li B. The conduction system and expressions of hyperpolarization-activated cyclic nucleotide-gated cation channel 4 and connexin43 expressions in the hearts of fetal day 13 mice. Biotech Histochem. 2017;92:86-91 pubmed publisher
    ..identify myocardial cells that express HCN4, hyperpolarization-activated cyclic nucleotide-gated cation channel 2 (HCN2) and Cx43...
  37. Pai V, Pietak A, Willocq V, Ye B, Shi N, Levin M. HCN2 Rescues brain defects by enforcing endogenous voltage pre-patterns. Nat Commun. 2018;9:998 pubmed publisher
    ..explains nicotine's effects via the disruption of endogenous bioelectrical gradients and predicts that exogenous HCN2 ion channels would restore the endogenous bioelectric prepatterns necessary for brain patterning...
  38. Yoshimoto R, Iwasaki S, Takago H, Nakajima T, Sahara Y, Kitamura K. Developmental increase in hyperpolarization-activated current regulates intrinsic firing properties in rat vestibular ganglion cells. Neuroscience. 2015;284:632-42 pubmed publisher
    ..that expression of HCN1 protein and its mRNA increased during the developmental period, whereas expression of HCN2-4 protein and its mRNA did not change...
  39. Deberg H, Brzovic P, Flynn G, Zagotta W, Stoll S. Structure and Energetics of Allosteric Regulation of HCN2 Ion Channels by Cyclic Nucleotides. J Biol Chem. 2016;291:371-81 pubmed publisher
    ..We explain these results with a model where different allosteric mechanisms in the CNBD all converge to have the same effect on the C-linker and render all three cyclic nucleotides similarly potent activators of the channel. ..
  40. Luo P, Lu Y, Li C, Zhou M, Chen C, Lu Q, et al. Long-lasting spatial learning and memory impairments caused by chronic cerebral hypoperfusion associate with a dynamic change of HCN1/HCN2 expression in hippocampal CA1 region. Neurobiol Learn Mem. 2015;123:72-83 pubmed publisher
    ..Expression of NeuN, HCN1 and HCN2 in hippocampal CA1, DG and CA3 areas was quantified by immunohistochemistry and western blotting...
  41. Itoh M, Ishihara K, Nakashima N, Takano M. The hyperpolarization-activated cyclic nucleotide-gated (HCN) channels contain multiple S-palmitoylation sites. J Physiol Sci. 2016;66:241-8 pubmed publisher
    ..Thus, we performed an acyl-biotinyl exchange assay, and found that HCN1, HCN2, and HCN4, but not HCN3, were S-palmitoylated in HEK293 cells...
  42. Alvarez Baron C, Klenchin V, Chanda B. Minimal molecular determinants of isoform-specific differences in efficacy in the HCN channel family. J Gen Physiol. 2018;150:1203-1213 pubmed publisher
    ..Cyclic AMP (cAMP) enhances the activity of HCN2 and HCN4 isoforms by shifting the voltage dependence of activation to more depolarized potentials, whereas HCN1 and ..
  43. Zhou M, Luo P, Lu Y, Li C, Wang D, Lu Q, et al. Imbalance of HCN1 and HCN2 expression in hippocampal CA1 area impairs spatial learning and memory in rats with chronic morphine exposure. Prog Neuropsychopharmacol Biol Psychiatry. 2015;56:207-14 pubmed publisher
    ..In the present study, we investigated the expression of HCN1 and HCN2 subunits in hippocampal CA1 and the potential molecular mechanisms underlying the modulation of HCN channels in ..
  44. Cho Y, Kim Y, Moozhayil S, Yang E, Bae Y. The expression of hyperpolarization-activated cyclic nucleotide-gated channel 1 (HCN1) and HCN2 in the rat trigeminal ganglion, sensory root, and dental pulp. Neuroscience. 2015;291:15-25 pubmed publisher
    Hyperpolarization-activated cyclic nucleotide-gated channel 1 (HCN1) and 2 (HCN2) are abundantly expressed in primary sensory neurons and contribute to neuronal excitability and pathological pain...
  45. Liu H, Zhou J, Gu L, Zuo Y. The change of HCN1/HCN2 mRNA expression in peripheral nerve after chronic constriction injury induced neuropathy followed by pulsed electromagnetic field therapy. Oncotarget. 2017;8:1110-1116 pubmed publisher
    ..model induced by chronic constriction injury (CCI) of sciatic nerve to evaluate the change of expression of HCN1/HCN2 mRNA in peripheral nerve and spinal cord...
  46. Zhong P, Vickstrom C, Liu X, Hu Y, Yu L, Yu H, et al. HCN2 channels in the ventral tegmental area regulate behavioral responses to chronic stress. elife. 2018;7: pubmed publisher
    ..Furthermore, shRNA-mediated HCN2 knockdown in the VTA was sufficient to recapitulate CMS-induced depressive- and anxiety-like behavior in stress-naï..
  47. Stallmeyer B, Kuß J, Kotthoff S, Zumhagen S, Vowinkel K, Rinné S, et al. A Mutation in the G-Protein Gene GNB2 Causes Familial Sinus Node and Atrioventricular Conduction Dysfunction. Circ Res. 2017;120:e33-e44 pubmed publisher
    ..this was in contrast to coexpression of mutant G?2-G?2 with other cardiac ion channels (HCN4, HCN2, and Cav1.2)...
  48. Lewis A, Vaidya S, Blaiss C, Liu Z, Stoub T, Brager D, et al. 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. 2011;31:7424-40 pubmed publisher
    ..We observed similar resistance to behavioral despair in distinct mutant mice lacking HCN1 or HCN2. These data demonstrate that interaction with the auxiliary subunit TRIP8b is a major mechanism underlying proper ..
  49. Liu X, Zhang L, Jin L, Tan Y, Li W, Tang J. HCN2 contributes to oxaliplatin-induced neuropathic pain through activation of the CaMKII/CREB cascade in spinal neurons. Mol Pain. 2018;14:1744806918778490 pubmed publisher
    ..However, the role of HCN2 in oxaliplatin-induced neuropathic pain remains unknown...
  50. Bárez López S, Hartley M, Grijota Martinez C, Scanlan T, Guadaño Ferraz A. Sobetirome and its amide prodrug Sob-AM2 exert thyromimetic actions in Mct8-deficient brain. Thyroid. 2018;: pubmed publisher
    ..In the heart, Hcn2 but not Atp2a2 expression was increased after treatment with the analogs...
  51. Sunkara M, Schwabe T, Ehrlich G, Kusch J, Benndorf K. All four subunits of HCN2 channels contribute to the activation gating in an additive but intricate manner. J Gen Physiol. 2018;150:1261-1271 pubmed publisher
    ..Here we analyze the effects of cAMP binding to different concatemers of HCN2 channel subunits, each having a defined number of functional CNBDs...
  52. Börger C, Schünke S, Lecher J, Stoldt M, Winkhaus F, Kaupp U, et al. Resonance assignment of the ligand-free cyclic nucleotide-binding domain from the murine ion channel HCN2. Biomol NMR Assign. 2015;9:243-6 pubmed publisher
    ..high-resolution structures of CNBDs from HCN and CNG channels are available, the gating mechanism for murine HCN2 channel, which leads to the opening of the channel pore, is still poorly understood...
  53. Boudreau Béland J, Duverger J, Petitjean E, Maguy A, Ledoux J, Comtois P. Spatiotemporal stability of neonatal rat cardiomyocyte monolayers spontaneous activity is dependent on the culture substrate. PLoS ONE. 2015;10:e0127977 pubmed publisher
    ..1 and HCN2 mRNA levels...
  54. Vanschouwen B, Melacini G. Regulation of HCN Ion Channels by Non-canonical Cyclic Nucleotides. Handb Exp Pharmacol. 2017;238:123-133 pubmed publisher
    ..primarily by cAMP, other cyclic nucleotides such as cGMP, cCMP, and cUMP serve as partial agonists for the HCN2 and HCN4 isoforms...
  55. Fan J, Stemkowski P, Gandini M, Black S, Zhang Z, Souza I, et al. Reduced Hyperpolarization-Activated Current Contributes to Enhanced Intrinsic Excitability in Cultured Hippocampal Neurons from PrP(-/-) Mice. Front Cell Neurosci. 2016;10:74 pubmed publisher
    ..However, neither HCN1 nor HCN2 formed a biochemical complex with PrP(C)...
  56. He W, Zhang J, Gan T, Xu G, Tang B. Expression of hyperpolarization-activated cyclic nucleotide-gated channel isoforms in a canine model of atrial fibrillation. Exp Ther Med. 2016;12:433-436 pubmed
    ..The mRNA and protein expression levels of HCN2 and HCN4 increased significantly in the AF group when compared with the sinus rhythm group...
  57. Liu Y, Feng Y, Zhang T. Pulsed Radiofrequency Treatment Enhances Dorsal Root Ganglion Expression of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels in a Rat Model of Neuropathic Pain. J Mol Neurosci. 2015;57:97-105 pubmed publisher
    ..HCN1 and HCN2 expression levels in the DRG were examined by immunohistochemistry and Western blot...
  58. Ng L, Putrenko I, Baronas V, Van Petegem F, Accili E. Cyclic Purine and Pyrimidine Nucleotides Bind to the HCN2 Ion Channel and Variably Promote C-Terminal Domain Interactions and Opening. Structure. 2016;24:1629-1642 pubmed publisher
    Cyclic AMP is thought to facilitate the opening of the HCN2 channel by binding to a C-terminal domain and promoting or inhibiting interactions between subunits...
  59. Günther A, Baumann A. Distinct expression patterns of HCN channels in HL-1 cardiomyocytes. BMC Cell Biol. 2015;16:18 pubmed publisher
    ..Gene expression profiles of hcn1, hcn2 and hcn4 were acutely affected during HL-1 cell propagation...
  60. Luo P, Zhang X, Lu Y, Chen C, Li C, Zhou M, et al. Fluoxetine ameliorates cognitive impairments induced by chronic cerebral hypoperfusion via down-regulation of HCN2 surface expression in the hippocampal CA1 area in rats. Pharmacol Biochem Behav. 2016;140:1-7 pubmed publisher
    ..Furthermore, 2VO caused an up-regulation of hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) surface expressions in the hippocampal CA1 area and fluoxetine also effectively recovered the disorder of HCN2 ..
  61. Bruzauskaite I, Bironaite D, Bagdonas E, Skeberdis V, Denkovskij J, Tamulevicius T, et al. Relevance of HCN2-expressing human mesenchymal stem cells for the generation of biological pacemakers. Stem Cell Res Ther. 2016;7:67 pubmed publisher
    ..of human mesenchymal stem cells (hMSCs) with the hyperpolarization-activated cyclic nucleotide-gated ion channel 2 (HCN2) gene has been demonstrated to provide biological pacing in dogs with complete heart block...
  62. Qin L, Wu V, Glass N. Deciphering the Regulatory Network between the SREBP Pathway and Protein Secretion in Neurospora crassa. MBio. 2017;8: pubmed publisher
    ..These findings have implications for our understanding of the cross talk of the SREBP and UPR pathways in other organisms and will guide the rational engineering of fungal strains to improve cellulolytic enzyme production. ..
  63. Della Santina L, Piano I, Cangiano L, Caputo A, Ludwig A, Cervetto L, et al. Processing of retinal signals in normal and HCN deficient mice. PLoS ONE. 2012;7:e29812 pubmed publisher
    ..mice models and of in vitro (patch-clamp) and in vivo (ERG) recordings of retinal activity we show that HCN1 and HCN2 channels are expressed at distinct retinal sites and serve different functions...
  64. Wolter S, Kloth C, Golombek M, Dittmar F, Försterling L, Seifert R. cCMP causes caspase-dependent apoptosis in mouse lymphoma cell lines. Biochem Pharmacol. 2015;98:119-31 pubmed publisher
    ..These two cell lines also lack PKG, hyperpolarization-activated cyclic nucleotide-gated channels 2 and 4 (HCN2 and HCN4) as assessed by real-time PCR...
  65. Heuermann R, JARAMILLO T, Ying S, Suter B, Lyman K, Han Y, et al. Reduction of thalamic and cortical Ih by deletion of TRIP8b produces a mouse model of human absence epilepsy. Neurobiol Dis. 2016;85:81-92 pubmed publisher
    ..In contrast to mice lacking the pore-forming HCN channel subunit HCN2, TRIP8b knockout mice exhibited normal cardiac and motor function and a less severe seizure phenotype...
  66. Ding W, You Z, Shen S, Yang J, Lim G, Doheny J, et al. Increased HCN Channel Activity in the Gasserian Ganglion Contributes to Trigeminal Neuropathic Pain. J Pain. 2018;19:626-634 pubmed publisher
    ..In the Gasserian ganglion, HCN1 and HCN2 are major HCN isoforms...
  67. Magee K, Madden Z, Young E. HCN Channel C-Terminal Region Speeds Activation Rates Independently of Autoinhibition. J Membr Biol. 2015;248:1043-60 pubmed publisher
    ..We used two-electrode voltage clamp on Xenopus oocytes to compare wildtype (WT) HCN2, a constitutively autoinhibited point mutant incapable of cAMP binding (HCN2 R591E), and derivatives with various C-..
  68. Eroli F, Vilotti S, van den Maagdenberg A, Nistri A. Hyperpolarization-activated current Ih in mouse trigeminal sensory neurons in a transgenic mouse model of familial hemiplegic migraine type-1. Neuroscience. 2017;351:47-64 pubmed publisher
    ..HCN1 and HCN2 were the most abundantly expressed subunits in TG, both in situ and in culture...
  69. He Q, Yu Y, Li G, Chen S. The Dome Wall of Bladder Acts as a Pacemaker Site in Detrusor Instability in Rats. Med Sci Monit. 2017;23:2400-2407 pubmed
    ..PCR assay and Western blot were used to assess the expression of HCN2 and Cx43...
  70. FISHER D, Luu P, Agarwal N, Kurz J, Chetkovich D. Loss of HCN2 leads to delayed gastrointestinal motility and reduced energy intake in mice. PLoS ONE. 2018;13:e0193012 pubmed publisher
    ..In mice, loss of HCN2 leads to cardiac dysrhythmias, persistent spike-wave discharges similar to those seen in absence epilepsy, ataxia, ..
  71. Huang X, Yang P, Yang Z, Zhang H, Ma A. Age-associated expression of HCN channel isoforms in rat sinoatrial node. Exp Biol Med (Maywood). 2016;241:331-9 pubmed publisher
    ..We found that HCN2 and HCN4 proteins were present in rat SAN using immunohistochemistry; therefore, we quantitatively analyzed their ..
  72. Resta F, Masi A, Sili M, Laurino A, Moroni F, Mannaioni G. Kynurenic acid and zaprinast induce analgesia by modulating HCN channels through GPR35 activation. Neuropharmacology. 2016;108:136-43 pubmed publisher
    ..b>HCN2, a subgroup of the HCN family channels, are heavily expressed in small dorsal root ganglia (DRG) neurons and their ..
  73. Ding W, You Z, Shen S, Chen L, Zhu S, Mao J. Inhibition of HCN channel activity in the thalamus attenuates chronic pain in rats. Neurosci Lett. 2016;631:97-103 pubmed publisher
    ..In the thalamus, immunoreactivity of both HCN1 and HCN2 subunits was increased in both rat models...
  74. Thon S, Schulz E, Kusch J, Benndorf K. Conformational Flip of Nonactivated HCN2 Channel Subunits Evoked by Cyclic Nucleotides. Biophys J. 2015;109:2268-76 pubmed publisher
    ..Using fcAMP, a fluorescent derivative of cAMP, we analyzed the effect of ligand binding on HCN2 channels not preactivated by voltage...
  75. Donahue J. Current state of the art for cardiac arrhythmia gene therapy. Pharmacol Ther. 2017;176:60-65 pubmed publisher
    ..Potential replacement of cardiac pacemakers has been shown for combination gene therapy using the HCN2 gene and either the gene for adenylate cyclase, the skeletal muscle isoform of the sodium channel, or a dominant ..
  76. Šatrauskienė A, Navickas R, Laucevičius A, Huber H. Identifying differential miR and gene consensus patterns in peripheral blood of patients with cardiovascular diseases from literature data. BMC Cardiovasc Disord. 2017;17:173 pubmed publisher
    ..Relating differentially expressed miRs to their putative gene targets using MirTarBase, we further identified HCN2/4 and LASP1 as potential markers of CAD and ACS, but not in HF...
  77. Resta F, Micheli L, Laurino A, Spinelli V, Mello T, Sartiani L, et al. Selective HCN1 block as a strategy to control oxaliplatin-induced neuropathy. Neuropharmacology. 2018;131:403-413 pubmed publisher
    ..Biochemically, we observed a downregulation of HCN2 expression and an upregulation of the HCN regulatory beta-subunit MirP1...
  78. Parker A, Welch M, Forster L, Tasneem S, Dubhashi J, Baro D. SUMOylation of the Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel 2 Increases Surface Expression and the Maximal Conductance of the Hyperpolarization-Activated Current. Front Mol Neurosci. 2016;9:168 pubmed publisher
    ..We hypothesized that SUMOylation might influence the surface expression of HCN2 channels. In this manuscript, we show that HCN2 channels are SUMOylated in the mouse brain...
  79. Vaccari T, Moroni A, Rocchi M, Gorza L, Bianchi M, Beltrame M, et al. The human gene coding for HCN2, a pacemaker channel of the heart. Biochim Biophys Acta. 1999;1446:419-25 pubmed
    ..We report here the identification of the human HCN2 gene and show that its functional expression in a human kidney cell line generates a current with properties ..
  80. Dekker J, Yellen G. Cooperative gating between single HCN pacemaker channels. J Gen Physiol. 2006;128:561-7 pubmed
    ..Here we present the first detailed single channel study of cloned mammalian HCN2. Excised patch clamp recordings revealed discrete hyperpolarization-activated, cAMP-sensitive channel openings with ..
  81. Boink G, Duan L, Nearing B, Shlapakova I, Sosunov E, Anyukhovsky E, et al. HCN2/SkM1 gene transfer into canine left bundle branch induces stable, autonomically responsive biological pacing at physiological heart rates. J Am Coll Cardiol. 2013;61:1192-201 pubmed publisher
    ..We implanted adenoviral SkM1, HCN2, or HCN2/SkM1 constructs into left bundle branches (LBB) or left ventricular (LV) epicardium of atrioventricular-..
  82. Schnorr S, Eberhardt M, Kistner K, Rajab H, Käßer J, Hess A, et al. HCN2 channels account for mechanical (but not heat) hyperalgesia during long-standing inflammation. Pain. 2014;155:1079-90 pubmed publisher
    ..However, the impact of HCN2 to chronic pain conditions is less clear and has not been examined so far...
  83. Li Y, Hong Y, Yusufuaji Y, Tang B, Zhou X, Xu G, et al. Altered expression of hyperpolarization-activated cyclic nucleotide-gated channels and microRNA-1 and -133 in patients with age-associated atrial fibrillation. Mol Med Rep. 2015;12:3243-3248 pubmed publisher
    ..It was hypothesized that age?dependent changes in HCN2, HCN4, miR?1 and miR?133 expression may contribute to age?associated atrial fibrillation, and therefore the ..
  84. Luo P, Chen C, Lu Y, Fu T, Lu Q, Xu X, et al. Baclofen ameliorates spatial working memory impairments induced by chronic cerebral hypoperfusion via up-regulation of HCN2 expression in the PFC in rats. Behav Brain Res. 2016;308:6-13 pubmed publisher
    ..Our results showed that 2VO caused striking spatial working memory impairments, accompanied with a decreased HCN2 expression in PFC, but the protein levels of protein gene product 9.5 (PGP9...
  85. Ding C, Yang C, Cao Q, Zhu X, Zhang J, Zhang W, et al. Effect of mHCN2 gene modification on chronotropic relevant receptors in BMSCs co-cultured with atrial myocytes. Exp Ther Med. 2017;14:2108-2116 pubmed publisher
    ..The present study assessed the effects of mouse (m)HCN2 gene modification on the expression of chronotropic relevant receptors, adrenergic receptor ?1 (Adrb1) and ..
  86. Lin H, Xiao J, Luo X, Chen G, Wang Z. Transcriptional control of pacemaker channel genes HCN2 and HCN4 by Sp1 and implications in re-expression of these genes in hypertrophied myocytes. Cell Physiol Biochem. 2009;23:317-26 pubmed publisher
    ..The pacemaker current I(f), carried by the hyperpolarization-activated channels encoded mainly by the HCN2 and HCN4 genes in the heart, plays an important role in rhythmogenesis...
  87. Klueva J, Lima A, Meis S, Voigt T, Munsch T. Hyperpolarization-activated cation current contributes to spontaneous network activity in developing neocortical cultures. Neurosignals. 2012;20:35-47 pubmed publisher
    ..Immunocytochemistry and Western blot demonstrated that HCN1 and HCN2 were the prevalent isoforms of HCN channels expressed in L-INs and PNs...
  88. Frykman S, Inoue M, Ikeda A, Teranishi Y, Kihara T, Lundgren J, et al. Maturation and processing of the amyloid precursor protein is regulated by the potassium/sodium hyperpolarization-activated cyclic nucleotide-gated ion channel 2 (HCN2). Biochem Biophys Res Commun. 2017;483:352-358 pubmed publisher
    ..of the purified proteins was potassium/sodium hyperpolarization-activated cyclic nucleotide-gated ion channel 2 (HCN2), which has been shown to be involved in epilepsy...
  89. Nakashima N, Nakashima K, Nakayama T, Takaku A, Kanamori R. Dual expression of constitutively active G?s-protein-coupled receptors differentially establishes the resting activity of the cAMP-gated HCN2 channel in a single compartment. Biochem Biophys Res Commun. 2017;494:76-81 pubmed publisher
    The hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2) channel is a major subtype of the HCN channel family expressed in the nervous system that sets the membrane potential, regulates cell excitability and senses changes in the ..
  90. Ludwig A, Zong X, Stieber J, Hullin R, Hofmann F, Biel M. Two pacemaker channels from human heart with profoundly different activation kinetics. EMBO J. 1999;18:2323-9 pubmed
    ..The hHCN2 cDNA codes for a protein of 889 amino acids. The HCN2 gene is localized on human chromosome 19p13.3 and contains eight exons spanning approximately 27 kb...
  91. Hofmann F, Biel M, Kaupp U. International Union of Pharmacology. LI. Nomenclature and structure-function relationships of cyclic nucleotide-regulated channels. Pharmacol Rev. 2005;57:455-62 pubmed
  92. Elinder F, Mannikko R, Pandey S, Larsson H. Mode shifts in the voltage gating of the mouse and human HCN2 and HCN4 channels. J Physiol. 2006;575:417-31 pubmed
    ..We found that HCN2 and HCN4 channels expressed in oocytes from the frog Xenopus laevis do not display the activation kinetic changes ..