Recombinant Mouse Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 (Hcn2), partial

1. rescues nicotine-exposed Xenopus embryos, restoring the endogenous bioelectric prepatterns necessary for brain patterning, resulting in normal brain morphology PMID: 29519998
2. Together, these results reveal a critical role for HCN2 in regulating ventral tegmental area dopamine neuronal activity and depressive-related behaviors. PMID: 29256865
3. the increased intracellular cAMP drives diabetes-associated pain by facilitating HCN2 activation and consequently promoting repetitive firing in primary nociceptive nerve fibers. PMID: 28954930
4. The data of this study strongly suggest that cAMP acts by PKA-mediated regulation of HCN2 channel activity and thereby generates nociceptive sensitization. PMID: 28767511
5. loss via insertion mutation leads to delayed gastrointestinal motility and reduced energy intake PMID: 29466436
6. Data support a model in which the degree of facilitation of opening in the full-length HCN2 channel by a given ligand depends upon its ability to promote oligomerization of the C-linker/cyclic nucleotide-binding domain in solution. PMID: 27568927
7. Mouse HCN2-expressing human mesenchymal stem cells are relevant biological models for the generation of biological pacemakers. PMID: 27137910
8. the allosteric mechanism of different cyclic nucleotides on the cyclic nucleotide-binding domain of HCN2 and on channel gating, was investigated. PMID: 26559974
9. HCN2 channel activity reduces the repolarization reserve of the ventricular action potential and increases ectopic automaticity under pathological conditions such as excessive beta-adrenergic stimulation. PMID: 25562801
10. fisetin is a partial agonist for HCN2 channels. PMID: 24085296
11. HCN2 channel expression increases significantly during pregnancy, accelerating the heart rate. PMID: 23609807
12. cAMP-dependent changes in the structure of the C-helix of a C-terminal fragment of HCN2 channels PMID: 23525108
13. cGKII and HCN2 interact and colocalize with each other PMID: 21347269
14. HCN2 shows only a confined expression to individual pacemaker cells. PMID: 21945247
15. findings show neuropathic pain is initiated by HCN2-driven action potential firing in Na(V)1.8-expressing nociceptors PMID: 21903816
16. new insights into the cAMP-dependent gating in HCN channel and the interpretation of protein allostery for general ligand-gated channels and receptors PMID: 21354395
17. HCN2 channels in inhibitory interneurons modulate synaptic plasticity in the perforant path by facilitating the GABAergic output onto pyramidal neurons. PMID: 20623157
18. results show that rendering rodents parkinsonian by DA depletion induces the downregulation of HCN channel expression in GPe neurons, leading to a loss of their characteristic autonomous pacemaking. PMID: 21076425
19. Here, we report that the mouse HCN2 pacemaker channel isoform also produced a large instantaneous current (I(inst(HCN2))) in addition to the well characterized, slowly activating I(h). PMID: 11741901
20. gating mechanisms in mouse HCN2 pacemaker channel and sensitivity to voltage, mutations and cations PMID: 12121985
21. a conserved domain in HCN2 is the critical NH(2)-terminal determinant of subunit co-assembly and trafficking of pacemaker channels PMID: 12193608
22. Results define the physiological role of the hyperpolarization-activated cation (HCN2) channel subunit as a major determinant of membrane resting potential that is required for regular cardiac and neuronal rhythmicity. PMID: 12514127
23. X-ray crystallographic structures of C-terminal fragment bound to cAMP or cGMP, identify a tetramerization domain and the mechanism for cyclic nucleotide specificity, and suggest a model for ligand-dependent channel modulation PMID: 12968185
24. a specific electrostatic interaction between Arg-339 of the S4-S5 linker and Asp-443 of the C-linker stabilizes the closed state and thus participates in the coupling of voltage sensing and activation gating in HCN channels. PMID: 14726518
25. In filamin- cells the gating kinetics of HCN1 were strongly accelerated relative to filamin+ cells. PMID: 15292205
26. Single-channel properties of cells cotransfected with mHCN2 & hHCN4 were distinct from cells expressing HCN2 or HCN4 alone. Different HCN isoforms influence current properties of a single HCN channel complex, providing for HCN heteromerization. PMID: 15687126
27. We propose that the cAMP-triggered large-scale oscillation plays an important role for the channel's function, being coupled to a motion of the C-linker which, in turn, modulates the gating of the channel. PMID: 16500960
28. Black Swiss mice have a single polymorphism in exon 2 within the Hcn2 gene, but we conclude that juvenile audiogenic seizures in Black Swiss mice are unlikely to be due to abnormalities of HCN2 channel function. PMID: 16542642
29. TASK3 and HCN2 channels stabilize the membrane potential by a mutual functional interactions. PMID: 16760342
30. With computer modelling, we show that in channels with relatively slow opening kinetics and fast mode-shift transitions, such as HCN2 and HCN4 channels, the mode shift effects are not readily observable, except in the tail kinetics. PMID: 16777944
31. Mouse HCN2 was injected into canine left bundle branch block increasing basal heart rate. PMID: 16923750
32. Thus, both native and recombinant HCN channels are regulated by PI(4,5)P(2). PMID: 17074978
33. HCN2-HCN4 heteromeric channels form in native tissue to make functional pacemaker channels PMID: 17553794
34. Using computer simulation and mutagenesis, ligand contacts important for the regulation of HCN2 by cyclic nucleotides were identified. PMID: 17562313
35. A site-directed mutagenesis approach was used to identify specific residues of the mouse HCN2 channel pore that interact with ZD7288. PMID: 17578902
36. Current through HCN2 and HCN3 channels confers regular and faster rhythmicity to mouse embryonic stem cells, which mirrors the developing embryonic mouse heart, and contributes to modulation of rhythmicity by autonomic stimulation. PMID: 18033814
37. Provide direct evidence for calcium conductance of HCN2 channels. PMID: 18252758
38. RPTPalpha plays a critical role in HCN channel function via tyrosine dephosphorylation PMID: 18768480
39. we characterized a novel spontaneous mutant, apathetic (ap/ap); identified ap mutation as a 4 base pair insertion in the coding region of Hcn2; ap/ap mice exhibited ataxia, generalized spike-wave absence seizures & rare generalized tonic-clonic seizures PMID: 19150498
40. Alanine/valine scan of the distal pore of the HCN2 isoform show that effects of mutations on channel opening and on the steepness of the response of the channel to voltage are mixed and smaller than those in Shaker channels. PMID: 19269964
41. functional myocardial I(f) channels reflect the heteromeric assembly of HCN2 and HCN4 subunits and further that the HCN4 subunit underlies the cAMP-mediated regulation of cardiac I(f) channels. PMID: 19574228

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KEGG: mmu:15166

STRING: 10090.ENSMUSP00000020581

UniGene: Mm.12956