Ask about this productRelated genes to: HCN2 antibody
- Gene:
- HCN2 NIH gene
- Name:
- hyperpolarization activated cyclic nucleotide gated potassium and sodium channel 2
- Previous symbol:
- BCNG2
- Synonyms:
- BCNG-2, HAC-1
- Chromosome:
- 19p13.3
- Locus Type:
- gene with protein product
- Date approved:
- 1998-08-20
- Date modifiied:
- 2017-05-23
Related products to: HCN2 antibody
Related articles to: HCN2 antibody
- Bladder cancer is one of the most common malignancies of the urinary system. Identifying new potential therapeutic targets and exploring molecular mechanisms are crucial for improving treatment and prognosis. The hyperpolarization-activated cyclic nucleotide-gated (HCN) channel 2, known to play a key role in various physiological and pathological processes, has an unclear function and mechanism of action in bladder cancer. We employed bioinformatics analysis and immunohistochemistry to assess the role of HCN2 in bladder cancer, integrating in vitro and in vivo models to evaluate the impact of HCN2 on cell behavior. Molecular interactions were characterized using immunoprecipitation, chromatin immunoprecipitation, and dual-luciferase reporter assays. Our investigation revealed a significant upregulation of HCN2 in bladder cancer tissues, which was predictive of a poorer clinical outcome. Functionally, HCN2 knockdown in bladder cancer impeded cell proliferation, induced apoptosis, and curtailed migration and invasion. Mechanistically, the overexpression of HCN2 contributed to the translocation of the REST transcription factor into the nucleus and facilitated its binding to the BGN promoter for transcriptional activation of its expression. This regulatory mechanism was shown to suppress ferroptosis, a form of regulated cell death, thereby enhancing the proliferative and tumorigenesis of bladder cancer cells. This study uncovers the novel mechanism by which HCN2 regulates ferroptosis via the REST-BGN axis, affecting bladder cancer cell behavior, and provides new perspectives and strategies for future clinical treatment. - Source: PubMed
Publication date: 2026/04/11
Cao YudongMa JinchaoTang XingxingCui YushuangYang XiaoJi YongpengYou RuijianLin ChenWang ShuoDu Peng - Rhythmic activity of specialized pacemaker neurons in the brain is necessary to control alertness and circadian timing. Four HCN channels have been identified to generate the pacemaker current I or I, differing in activation speed, voltage dependence, single-channel conductance, and cAMP sensitivity. Here we show the time-resolved operation of single HCN1, HCN2 and HCN4 channels during the pacemaker depolarization using a dynamic neuronal action potential clamp at femtosiemens resolution. All channels produce a relevant open probability during pacemaker depolarization. However, only mHCN1 channels are significantly activated and deactivated in action potential cycles whereas the gating in mHCN2 and mHCN4 channels is at best barely resolvable and too slow. Simulations suggest that the role of HCN1 channels is to trigger the initial neuronal pacemaker depolarization before other depolarizing conductances take over this role. In conclusion, mHCN1 channels are the primary HCN pacemaker channels that operate as trigger channels for pacemaking. - Source: PubMed
Publication date: 2026/04/23
Enke UtaSchweinitz AndreaTewari DebanjanSattler ChristianSchmauder RalfSchmidt-Hieber ChristophBenndorf Klaus - Hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2) channels regulate action potential firing in nociceptors and are critical mediators of neuronal hyperexcitability in response to inflammation and nerve injury. These channels are activated by membrane hyperpolarization and potentiated by direct cAMP binding to their C-terminal cyclic nucleotide-binding domain (CNBD). Although a role for cAMP in modulating HCN2 activity and contributing to neuropathic pain has been hypothesized, direct evidence has been lacking. To test this causal link, here we employ TRIP8b, comprising a minimal peptide derivative from the brain protein TRIP8b that selectively antagonizes cAMP binding to HCN channels. TRIP8b effectively abolished cAMP-mediated potentiation of HCN2 currents in small-diameter dorsal root ganglion (DRG) neurons, validating its utility as a functional inhibitor. In a rat model of neuropathic pain, DRG-targeted expression of TRIP8b significantly reduced mechanical and thermal hypersensitivity. These findings provide the first direct evidence that cAMP binding to HCN2 channels drives nociceptor hyperexcitability and neuropathic pain and establishes disruption of this interaction as a promising therapeutic strategy. KEY POINTS: Activation of HCN2 channels is potentiated by cAMP binding to their cyclic nucleotide binding domain (CNBD). TRIP8b abolishes cAMP binding to CNBD, thus inhibiting potentiation of HCN2 currents in both HEK 293T cells and rat DRG neurons. TRIP8b reduces mechanical and thermal hypersensitivity in a rat model of neuropathic pain. Our findings confirm a direct role of cAMP-HCN2 signalling in neuropathic pain and suggest a new therapeutic target. - Source: PubMed
Publication date: 2026/04/20
Loya-Lopez Santiago IGomez KimberlyPorro AlessandroThiel GerhardMoroni AnnaAllen Heather NKhanna RajeshSaponaro Andrea - Epilepsy is a chronic pathophysiological syndrome defined by excessive and recurrent neuronal electrical discharges in the brain, affecting approximately 0.8% of the global population. The concept of channelopathy emerges as a fundamental basis for this dysfunction, involving failures in voltage-gated ion channels. Among these, hyperpolarization-activated cation channels (HCN), encoded by the HCN1-4 genes, are unique due to their pacemaker function and sensitivity to abnormal electrical activity, regulating resting membrane potential and neuronal excitability. - Source: PubMed
Publication date: 2026/03/26
Dos Santos Ricardo SilvaDos Santos Maria de Fátima Castroda Costa Jaderson CostaMachado Denise CantarelliAntocheviez Giovana NascimentoLima Natan LuccaMezzari Marcos Henrique da SilvaIsolan Gustavo Rassier - Our prior research demonstrated that the neuroprotective effects of clonidine can be reversed by yohimbine, an α2-adrenergic receptor antagonist. Additionally, clonidine has been shown to alleviate anxiety-like behavior in rats after bilateral common carotid artery occlusion by reducing the expression of proteins associated with hyperpolarization-activated cyclic nucleotide-gated (HCN) cation channels. However, the specific mechanisms by which clonidine inhibits HCN channels remain unclear. This study was designed to explore the protective effects of clonidine on neurons subjected to oxygen-glucose deprivation (OGD) injury and elucidate the underlying molecular mechanisms via HCN channels. The protective effects of clonidine on OGD-exposed neurons were confirmed by assessing the neuronal viability using a cell counting kit-8 (CCK-8) assay and by measuring the lactate dehydrogenase (LDH) release. Moreover, we identified the signaling pathways most relevant to clonidine’s action. PCR was performed to assess the PKA, AKT, HCN1, and HCN2 gene expressions, and a western blot assay was used to evaluate the related protein expressions of the AC–cAMP–PKA cascade, the PIK/Akt pathway, and the HCN channels. Clonidine and ZD7288 individually enhanced neuronal viability under OGD, demonstrating neuroprotective effects, with their combination yielding greater benefit. Clonidine upregulated α2A-AR and Nischarin protein levels. Its protection was attenuated by yohimbine (an α2-AR antagonist) and, to a lesser extent, by efaroxan (an I1R antagonist). KT5720, an AC–cAMP–PKA pathway inhibitor, synergized with clonidine and suppressed OGD-induced increases in HCN1 and HCN2 expression. Conversely, LY294002, a PI3K/Akt inhibitor, counteracted clonidine’s protection and further enhanced HCN1/HCN2 expression. These findings indicate that clonidine protects against OGD-induced injury mainly via α2-AR and partially through I1R, potentially by modulating HCN channels via the AC–cAMP–PKA and PI3K/Akt pathways. - Source: PubMed
Publication date: 2026/03/26
Wang KeYan Wen-JingLi GangLiu JueChen YueLi Zi-ChengHe Zhi