Hcn4

Summary

Gene Symbol: Hcn4
Description: hyperpolarization-activated, cyclic nucleotide-gated K+ 4
Alias: Bcng3, Hcn3, potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4, BCNG-3, brain cyclic nucleotide-gated channel 3, hyperpolarization-activated, cyclic nucleotide-gated K+ 3
Species: mouse
Products:     Hcn4

Top Publications

  1. Bakker M, Boukens B, Mommersteeg M, Brons J, Wakker V, Moorman A, et al. Transcription factor Tbx3 is required for the specification of the atrioventricular conduction system. Circ Res. 2008;102:1340-9 pubmed publisher
    ..Our data suggest a mechanism in which Tbx3 represses differentiation into ventricular working myocardium, thereby imposing the conduction system phenotype on cells within its expression domain. ..
  2. 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
  3. Christoffels V, Mommersteeg M, Trowe M, Prall O, de Gier de Vries C, Soufan A, et al. Formation of the venous pole of the heart from an Nkx2-5-negative precursor population requires Tbx18. Circ Res. 2006;98:1555-63 pubmed
  4. Herrmann S, Stieber J, Stöckl G, Hofmann F, Ludwig A. HCN4 provides a 'depolarization reserve' and is not required for heart rate acceleration in mice. EMBO J. 2007;26:4423-32 pubmed
    ..We have now studied mice in which the predominant sinoatrial HCN channel isoform HCN4 was deleted in a temporally controlled manner...
  5. Harzheim D, Pfeiffer K, Fabritz L, Kremmer E, Buch T, Waisman A, et al. Cardiac pacemaker function of HCN4 channels in mice is confined to embryonic development and requires cyclic AMP. EMBO J. 2008;27:692-703 pubmed publisher
    ..We studied the role of I(f) in mice, in which binding of cAMP to HCN4 channels was abolished by a single amino-acid exchange (R669Q)...
  6. Später D, Abramczuk M, Buac K, Zangi L, Stachel M, Clarke J, et al. A HCN4+ cardiomyogenic progenitor derived from the first heart field and human pluripotent stem cells. Nat Cell Biol. 2013;15:1098-106 pubmed publisher
    ..Here, we present Hcn4 (hyperpolarization-activated cyclic nucleotide-gated channel 4) as an FHF marker...
  7. Herrmann S, Layh B, Ludwig A. Novel insights into the distribution of cardiac HCN channels: an expression study in the mouse heart. J Mol Cell Cardiol. 2011;51:997-1006 pubmed publisher
    ..The specificity of antibodies used was strictly confirmed by the use of HCN1, HCN2 and HCN4 knockout animals...
  8. Herrmann S, Fabritz L, Layh B, Kirchhof P, Ludwig A. Insights into sick sinus syndrome from an inducible mouse model. Cardiovasc Res. 2011;90:38-48 pubmed publisher
    ..We crossed two genetically engineered mouse lines, ROSA-eGFP-DTA and HCN4-KiT-Cre, to achieve an inducible deletion of cells specifically in the cardiac pacemaking and conduction system...
  9. Wang J, Klysik E, Sood S, Johnson R, Wehrens X, Martin J. Pitx2 prevents susceptibility to atrial arrhythmias by inhibiting left-sided pacemaker specification. Proc Natl Acad Sci U S A. 2010;107:9753-8 pubmed publisher
    ..Our findings implicate Pitx2 and Pitx2-mediated LRA-signaling pathways in prevention of atrial arrhythmias. ..

More Information

Publications62

  1. Wiese C, Grieskamp T, Airik R, Mommersteeg M, Gardiwal A, de Gier de Vries C, et al. Formation of the sinus node head and differentiation of sinus node myocardium are independently regulated by Tbx18 and Tbx3. Circ Res. 2009;104:388-97 pubmed publisher
    ..Our data establish a functional order for Tbx18 and Tbx3 in SAN formation, in which Tbx18 controls the formation of the SAN head from mesenchymal precursors, on which Tbx3 subsequently imposes the pacemaker gene program. ..
  2. Hoesl E, Stieber J, Herrmann S, Feil S, Tybl E, Hofmann F, et al. Tamoxifen-inducible gene deletion in the cardiac conduction system. J Mol Cell Cardiol. 2008;45:62-9 pubmed publisher
    ..The tamoxifen-inducible CreER(T2) construct was 'knocked in' into the pacemaker channel HCN4 locus. In the absence of inducing agent, recombination was undetectable in HCN4-KiT mice...
  3. Espinoza Lewis R, Liu H, Sun C, Chen C, Jiao K, Chen Y. Ectopic expression of Nkx2.5 suppresses the formation of the sinoatrial node in mice. Dev Biol. 2011;356:359-69 pubmed publisher
    ..Taken together, our results demonstrate that Shox2 downregulation of Nkx2.5 is essential for the proper development of the SAN and that Shox2 functions to shield the SAN from becoming working myocardium by acting upstream of Nkx2.5. ..
  4. Liu H, Chen C, Espinoza Lewis R, Jiao Z, Sheu I, Hu X, et al. Functional redundancy between human SHOX and mouse Shox2 genes in the regulation of sinoatrial node formation and pacemaking function. J Biol Chem. 2011;286:17029-38 pubmed publisher
    ..The SHOX/Shox2 dose appears to be critical for normal pacemaking function. ..
  5. Baruscotti M, Bucchi A, Viscomi C, Mandelli G, Consalez G, Gnecchi Rusconi T, et al. Deep bradycardia and heart block caused by inducible cardiac-specific knockout of the pacemaker channel gene Hcn4. Proc Natl Acad Sci U S A. 2011;108:1705-10 pubmed publisher
    ..molecular constituents are the hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels and particularly HCN4, work with mice where Hcn genes were knocked out, or functionally modified, has challenged this view...
  6. Espinoza Lewis R, Yu L, He F, Liu H, Tang R, Shi J, et al. Shox2 is essential for the differentiation of cardiac pacemaker cells by repressing Nkx2-5. Dev Biol. 2009;327:376-85 pubmed publisher
    ..Genetically, the lack of Tbx3 and Hcn4 expression, along with ectopic activation of Nppa, Cx40, and Nkx2-5 in the Shox2(-/-) SAN region, indicates a ..
  7. Stieber J, Herrmann S, Feil S, Löster J, Feil R, Biel M, et al. The hyperpolarization-activated channel HCN4 is required for the generation of pacemaker action potentials in the embryonic heart. Proc Natl Acad Sci U S A. 2003;100:15235-40 pubmed
    ..Transcripts of the HCN4 isoform have been found in cardiomyocytes and neurons, but the physiological role of this channel is unknown...
  8. Mommersteeg M, Hoogaars W, Prall O, de Gier de Vries C, Wiese C, Clout D, et al. Molecular pathway for the localized formation of the sinoatrial node. Circ Res. 2007;100:354-62 pubmed
    ..genetic models, we show that as the myocardium of the heart tube matures, Nkx2-5 suppresses pacemaker channel gene Hcn4 and T-box transcription factor gene Tbx3, thereby enforcing a progressive confinement of their expression to the ..
  9. Whitaker G, Angoli D, Nazzari H, Shigemoto R, Accili E. HCN2 and HCN4 isoforms self-assemble and co-assemble with equal preference to form functional pacemaker channels. J Biol Chem. 2007;282:22900-9 pubmed
    ..Previous studies have suggested that the HCN2 and HCN4 channel isoforms physically interact when overexpressed in mammalian cells, but whether they are able to co-..
  10. Sun Y, Liang X, Najafi N, Cass M, Lin L, Cai C, et al. Islet 1 is expressed in distinct cardiovascular lineages, including pacemaker and coronary vascular cells. Dev Biol. 2007;304:286-96 pubmed
    ..Our studies suggest a role for Isl1 in these distinct domains of expression within the heart. ..
  11. Schweizer P, Yampolsky P, Malik R, Thomas D, Zehelein J, Katus H, et al. Transcription profiling of HCN-channel isotypes throughout mouse cardiac development. Basic Res Cardiol. 2009;104:621-9 pubmed publisher
    ..5 dpc to postnatal day 120 in the mouse. Embryonic atrium and ventricle revealed abundant HCN4 transcription but other HCN transcripts were almost absent...
  12. Liang X, Wang G, Lin L, Lowe J, Zhang Q, Bu L, et al. HCN4 dynamically marks the first heart field and conduction system precursors. Circ Res. 2013;113:399-407 pubmed publisher
    ..To investigate HCN4 as a marker for the first heart field and for precursors of distinct components of the CCS, and to gain insight ..
  13. Duan X, Krishnaswamy A, De la Huerta I, Sanes J. Type II cadherins guide assembly of a direction-selective retinal circuit. Cell. 2014;158:793-807 pubmed publisher
    ..Our results reveal cellular components of a retinal circuit and demonstrate roles of type II cadherins in synaptic choice and circuit function. ..
  14. Mommersteeg M, Andrews W, Ypsilanti A, Zelina P, Yeh M, Norden J, et al. Slit-roundabout signaling regulates the development of the cardiac systemic venous return and pericardium. Circ Res. 2013;112:465-75 pubmed publisher
    ..Reduced Slit3 binding in the absence of Robo1, causing impaired cardiac neural crest survival, adhesion, and migration, underlies the pericardial defects. ..
  15. Sebastian S, Ang R, Abramowitz J, Weinstein L, Chen M, Ludwig A, et al. The in vivo regulation of heart rate in the murine sinoatrial node by stimulatory and inhibitory heterotrimeric G proteins. Am J Physiol Regul Integr Comp Physiol. 2013;305:R435-42 pubmed publisher
    ..We conclude that G?s- and G?i2-mediated signaling in the sinoatrial node is important in the reciprocal regulation of heart rate through the autonomic nervous system. ..
  16. Garcia Frigola C, Shi Y, Evans S. Expression of the hyperpolarization-activated cyclic nucleotide-gated cation channel HCN4 during mouse heart development. Gene Expr Patterns. 2003;3:777-83 pubmed
    b>HCN4 is a hyperpolarization-activated nucleotide-gated cation channel involved in the generation of the I(f) current that drives cardiac pacemaker activity...
  17. Abbas S, Ying S, Goldstein P. Compartmental distribution of hyperpolarization-activated cyclic-nucleotide-gated channel 2 and hyperpolarization-activated cyclic-nucleotide-gated channel 4 in thalamic reticular and thalamocortical relay neurons. Neuroscience. 2006;141:1811-25 pubmed
    ..have been identified, and mRNAs and proteins for HCN channels have been detected in the RTN and VB, with HCN2 and HCN4 being the predominant isoforms...
  18. Hoffmann S, Berger I, Glaser A, Bacon C, Li L, Gretz N, et al. Islet1 is a direct transcriptional target of the homeodomain transcription factor Shox2 and rescues the Shox2-mediated bradycardia. Basic Res Cardiol. 2013;108:339 pubmed publisher
    ..Our findings demonstrate a novel epistatic relationship between Shox2 and Isl1 in the heart with important developmental consequences for SAN formation and heart beat. ..
  19. Norden J, Grieskamp T, Lausch E, van Wijk B, van den Hoff M, Englert C, et al. Wt1 and retinoic acid signaling in the subcoelomic mesenchyme control the development of the pleuropericardial membranes and the sinus horns. Circ Res. 2010;106:1212-20 pubmed publisher
    ..Thus, our results provide novel insight into the genetic and cellular pathways regulating the posterior extension of the mammalian heart and the formation of its coelomic lining. ..
  20. Wicks N, Chan K, Madden Z, Santoro B, Young E. Sensitivity of HCN channel deactivation to cAMP is amplified by an S4 mutation combined with activation mode shift. Pflugers Arch. 2009;458:877-89 pubmed publisher
    ..We isolated a mutation (lysine 381 to glutamate) in S4 of mouse HCN4; patch-clamp of homomeric channels in excised inside-out membranes revealed a conditional phenotype...
  21. Fujii M, Sakaguchi A, Kamata R, Nagao M, Kikuchi Y, Evans S, et al. Sfrp5 identifies murine cardiac progenitors for all myocardial structures except for the right ventricle. Nat Commun. 2017;8:14664 pubmed publisher
    ..These findings provide insight into the arrangement of cardiac progenitors for systemic circulation. ..
  22. Al Madhoun A, Voronova A, Ryan T, Zakariyah A, McIntire C, Gibson L, et al. Testosterone enhances cardiomyogenesis in stem cells and recruits the androgen receptor to the MEF2C and HCN4 genes. J Mol Cell Cardiol. 2013;60:164-71 pubmed publisher
    ..5, muscle structural proteins, and the pacemaker ion channel HCN4 in a dose-dependent manner, in mES cells and P19 embryonal carcinoma cells...
  23. Baker C, Taylor D, Osuala K, Natarajan A, Molnar P, Hickman J, et al. Adrenergic deficiency leads to impaired electrical conduction and increased arrhythmic potential in the embryonic mouse heart. Biochem Biophys Res Commun. 2012;423:536-41 pubmed publisher
  24. Wu C, Dong X, Liu Q, Zhu J, Zhang T, Wang Q, et al. EP3 activation facilitates bladder excitability via HCN channels on ICCs. Biochem Biophys Res Commun. 2017;485:535-541 pubmed publisher
    ..Western blot analyses showed that the expression levels of HCN1 and HCN4 were higher in bladders that had undergone intravesical instillation with sulprostone than in bladders treated with ..
  25. Vedantham V, Evangelista M, Huang Y, Srivastava D. Spatiotemporal regulation of an Hcn4 enhancer defines a role for Mef2c and HDACs in cardiac electrical patterning. Dev Biol. 2013;373:149-62 pubmed publisher
    ..elements that control expression of the hyperpolarization-activated cyclic-nucleotide gated ion channel 4 (Hcn4)...
  26. Jongbloed M, Vicente Steijn R, Douglas Y, Wisse L, Mori K, Yokota Y, et al. Expression of Id2 in the second heart field and cardiac defects in Id2 knock-out mice. Dev Dyn. 2011;240:2561-77 pubmed publisher
    ..Expression patterns of Id2, MLC-2a, Nkx2.5, HCN4, and WT-1 were analyzed...
  27. Zhang S, Kim K, Rosén A, Smyth J, Sakuma R, Delgado Olguin P, et al. Iroquois homeobox gene 3 establishes fast conduction in the cardiac His-Purkinje network. Proc Natl Acad Sci U S A. 2011;108:13576-81 pubmed publisher
    ..Irx3 directly represses Cx43 transcription and indirectly activates Cx40 transcription. Our results reveal a critical role for Irx3 in the precise regulation of intercellular gap junction coupling and impulse propagation in the heart. ..
  28. Saito M, Sasaki T, Matsuoka H. Vitamin B(12) promotes Cx40 and HCN4 gene expression at an early stage of cardiomyocyte differentiation. Exp Anim. 2009;58:57-60 pubmed
    ..When VB(12) (0.5 mM) was added to the medium on day 3 of culture, the levels of Cx40 and HCN4 expression increased over those in the control, 2 to 3 days before the start of cardiomyocyte beating...
  29. Tong S, Yao Q, Wan Y, Zhou J, Shu M, Zhong L, et al. Development of functional I f channels in mMSCs after transfection with mHCN4: effects on cell morphology and mechanical activity in vitro. Cardiology. 2009;112:114-21 pubmed publisher
    ..66 +/- 23 bmp, p < 0.01). Functional I(f) channels can be reconstructed in mMSCs infected with mHCN4. mMSCs modified by successful transfection with mHCN4 can differentiate so as to develop spontaneous mechanical activity. ..
  30. Christel C, Cardona N, Mesirca P, Herrmann S, Hofmann F, Striessnig J, et al. Distinct localization and modulation of Cav1.2 and Cav1.3 L-type Ca2+ channels in mouse sinoatrial node. J Physiol. 2012;590:6327-42 pubmed publisher
    ..We conclude that strong VDF and colocalization with ryanodine receptors in mouse SAN cells are unique properties that may underlie a specific role for Ca(v)1.3 in opposing abnormal slowing of heart rate. ..
  31. Fried H, Kaupp U, Muller F. Hyperpolarization-activated and cyclic nucleotide-gated channels are differentially expressed in juxtaglomerular cells in the olfactory bulb of mice. Cell Tissue Res. 2010;339:463-79 pubmed publisher
    ..Four channel isoforms exist (HCN1-HCN4) that can form homo- or heteromers...
  32. 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
    ..of the heart conduction system by localizing hyperpolarization-activated cyclic nucleotide-gated cation channel 4 (HCN4) and connexin43 (Cx43) in the hearts of fetal day 13 mice...
  33. Benes J, Ammirabile G, Sankova B, Campione M, Krejci E, Kvasilova A, et al. The role of connexin40 in developing atrial conduction. FEBS Lett. 2014;588:1465-9 pubmed publisher
    ..Cx40 has thus an important physiological role in the developing atria. ..
  34. Scavone A, Capilupo D, Mazzocchi N, Crespi A, Zoia S, Campostrini G, et al. Embryonic stem cell-derived CD166+ precursors develop into fully functional sinoatrial-like cells. Circ Res. 2013;113:389-98 pubmed publisher
    ..We found that in embryonic day 10.5 mouse hearts, CD166 and HCN4, markers of the pacemaker tissue, are coexpressed...
  35. Gros D, Théveniau Ruissy M, Bernard M, Calmels T, Kober F, Sohl G, et al. Connexin 30 is expressed in the mouse sino-atrial node and modulates heart rate. Cardiovasc Res. 2010;85:45-55 pubmed publisher
    ..transgenic mice with reporter genes (Cx30(LacZ/LacZ) and Cx30(LacZ/LacZ)/Cx40(EGFP/EGFP) mice), as well as anti-HCN4 (hyperpolarization activated cyclic nucleotide-gated potassium channel 4) or anti-connexin antibodies...
  36. Liang X, Zhang Q, Cattaneo P, Zhuang S, Gong X, Spann N, et al. Transcription factor ISL1 is essential for pacemaker development and function. J Clin Invest. 2015;125:3256-68 pubmed publisher
  37. Morita Y, Andersen P, Hotta A, Tsukahara Y, Sasagawa N, Hayashida N, et al. Sall1 transiently marks undifferentiated heart precursors and regulates their fate. J Mol Cell Cardiol. 2016;92:158-62 pubmed publisher
    ..These findings provide fundamental insights into CPC maintenance, which can be instrumental for CPC-based regenerative medicine. ..
  38. Nakashima Y, Yanez D, Touma M, Nakano H, Jaroszewicz A, Jordan M, et al. Nkx2-5 suppresses the proliferation of atrial myocytes and conduction system. Circ Res. 2014;114:1103-13 pubmed publisher
    ..Collectively, these data suggest that Nkx2-5 regulates the proliferation of atrial working and conduction myocardium in coordination with Notch pathway. ..
  39. Liao Z, Lockhead D, Larson E, Proenza C. Phosphorylation and modulation of hyperpolarization-activated HCN4 channels by protein kinase A in the mouse sinoatrial node. J Gen Physiol. 2010;136:247-58 pubmed publisher
    ..I(f) is produced by hyperpolarization-activated cyclic nucleotide-sensitive (HCN4) channels, which can be potentiated by direct binding of cAMP to a conserved cyclic nucleotide binding domain in ..
  40. Wicks N, Wong T, Sun J, Madden Z, Young E. Cytoplasmic cAMP-sensing domain of hyperpolarization-activated cation (HCN) channels uses two structurally distinct mechanisms to regulate voltage gating. Proc Natl Acad Sci U S A. 2011;108:609-14 pubmed publisher
    ..Thus the liganded and the unliganded forms of the CSD respectively provide the structural determinants for open-state trapping and autoinhibition, such that two distinct mechanisms for cAMP regulation can operate in one receptor. ..
  41. Li C, Zhang Q, Teng B, Mustafa S, Huang J, Yu H. Src tyrosine kinase alters gating of hyperpolarization-activated HCN4 pacemaker channel through Tyr531. Am J Physiol Cell Physiol. 2008;294:C355-62 pubmed
    ..inhibitor of Src tyrosine kinase, 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2), on HCN4 and its mutant channels expressed in HEK 293 cells by using a whole cell patch-clamp technique...
  42. Greulich F, Trowe M, Leffler A, Stoetzer C, Farin H, Kispert A. Misexpression of Tbx18 in cardiac chambers of fetal mice interferes with chamber-specific developmental programs but does not induce a pacemaker-like gene signature. J Mol Cell Cardiol. 2016;97:140-9 pubmed publisher
  43. Hofmann F, Fabritz L, Stieber J, Schmitt J, Kirchhof P, Ludwig A, et al. Ventricular HCN channels decrease the repolarization reserve in the hypertrophic heart. Cardiovasc Res. 2012;95:317-26 pubmed publisher
    ..Of the four HCN (hyperpolarization-activated cyclic nucleotide-gated channels) isoforms mediating I(f), HCN2 and HCN4 were the predominantly expressed subunits in healthy as well as hypertrophied hearts...
  44. Zakariyah A, Rajgara R, Veinot J, Skerjanc I, Burgon P. Congenital heart defect causing mutation in Nkx2.5 displays in vivo functional deficit. J Mol Cell Cardiol. 2017;105:89-98 pubmed publisher
    ..Collectively, the present study demonstrates that mice with the R141C point mutation in the Nkx2.5 allele phenocopies humans with the NKX2.5 R142C point mutation. ..
  45. 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...
  46. Simmons O, Snider P, Wang J, Schwartz R, Chen Y, Conway S. Persistent Noggin arrests cardiomyocyte morphogenesis and results in early in utero lethality. Dev Dyn. 2015;244:457-67 pubmed publisher
    ..region, failed to express the potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 (Hcn4), resulting in an overall decrease in Hcn4 levels...
  47. Lescroart F, Chabab S, Lin X, Rulands S, Paulissen C, Rodolosse A, et al. Early lineage restriction in temporally distinct populations of Mesp1 progenitors during mammalian heart development. Nat Cell Biol. 2014;16:829-40 pubmed publisher
  48. Santoro B, Grant S, Bartsch D, Kandel E. 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. 1997;94:14815-20 pubmed
    ..These findings suggest the existence of a new type of ion channel, which is potentially able to modulate membrane excitability in the brain and could respond to regulation by cyclic nucleotides. ..
  49. Sah R, Mesirca P, Van den Boogert M, Rosen J, MABLY J, Mangoni M, et al. Ion channel-kinase TRPM7 is required for maintaining cardiac automaticity. Proc Natl Acad Sci U S A. 2013;110:E3037-46 pubmed publisher
    ..significantly reduces spontaneous Ca(2+) transient firing rates and is associated with robust down-regulation of Hcn4, Cav3.1, and SERCA2a mRNA...
  50. Herrmann S, Lipp P, Wiesen K, Stieber J, Nguyen H, Kaiser E, et al. The cardiac sodium-calcium exchanger NCX1 is a key player in the initiation and maintenance of a stable heart rhythm. Cardiovasc Res. 2013;99:780-8 pubmed publisher
    ..Furthermore, Ca(2+) transients measured during electrical field stimulation were of smaller magnitude and decelerated kinetics in KO cells. Our results establish NCX1 as a critical target for the proper function of cardiac pacemaking. ..
  51. Nof E, Antzelevitch C, Glikson M. The Contribution of HCN4 to normal sinus node function in humans and animal models. Pacing Clin Electrophysiol. 2010;33:100-6 pubmed publisher
    ..Humans carrying HCN4 mutations indeed display significant bradycardia...
  52. Kuwahara K, Saito Y, Takano M, Arai Y, Yasuno S, Nakagawa Y, et al. NRSF regulates the fetal cardiac gene program and maintains normal cardiac structure and function. EMBO J. 2003;22:6310-21 pubmed
    ..Our results indicate NRSF to be a key transcriptional regulator of the fetal cardiac gene program and suggest an important role for NRSF in maintaining normal cardiac structure and function. ..
  53. Peng S, Wu J, Zhang D, Jiang C, Xie C, Liu T. Contribution of presynaptic HCN channels to excitatory inputs of spinal substantia gelatinosa neurons. Neuroscience. 2017;358:146-157 pubmed publisher
    ..We found that the expression of the HCN channel isoforms was varied in SG. The HCN4 isoform showed the highest level of co-localization with VGLUT2 (23±3%)...