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
- Sensory neurons are endowed with physiological characteristics that facilitate accurate signal extraction from stimuli. The functional importance of such properties is exemplified in auditory neurons where intrinsic excitability is optimized to detect frequency-specific features. In birds, the neurons of nucleus magnocellularis (NM) receive primary auditory inputs that are spatially arranged according to best frequency, or 'tonotopically.' Several physiological properties vary systematically along NM's tonotopic axis. Gradients of voltage-gated channels shape temporal response selectivity enabling precise encoding of sound features. We identified a previously undescribed expression pattern of hyperpolarization-activated cation (HCN) channels in the domestic chick Electrophysiological and immunohistochemical analyses demonstrated a tonotopic gradient of HCN1 but not HCN2 subunits that underlie currents along NM's tonotopic axis. To measure the effect of on membrane excitability along the tonotopy, we applied depolarizing current ramps prior to and during pharmacological block. We show exerts a strong influence on temporal integration properties of NM membranes. Next, we investigated whether this response modulation facilitates encoding of temporally patterned inputs by injecting depolarizing current pulse trains to simulate synaptic excitatory drive. During block, spike entrainment failed at high input rates suggesting HCN channels contribute strongly to NM's temporal selectivity. Computational modeling extended these results to show a contribution of to high frequency neuron responses in the presence of noise. This work establishes a tonotopic distribution of HCN channels in NM and demonstrates its contributions to temporal response selectivity, particularly at high frequencies. This study is the first to describe a tonotopic gradient of HCN channels in a vertebrate cochlear nucleus. Experimental assays and computational modeling demonstrate that the tonotopic expression pattern of HCN channels enables improved neural encoding of temporally patterned excitatory drive at high synaptic input rates. Temporal response fidelity in this circuit is required for precise sound localization. This work provides compelling evidence suggesting that HCN channel expression is regulated to optimize computational precision in sensory processing. - Source: PubMed
Publication date: 2026/09/02
Owusu-Nyantakyi KwameHamlette Lashaka SAshida GoWeimann SoniaOline Stefan NMichael Burger R - Alzheimer's disease (AD), though defined as a cognitive disorder, often presents neuropsychiatric symptoms such as anxiety, depression, agitation, and sleep disruptions years before the onset of frank memory impairment. An early pathological feature is the accumulation of hyperphosphorylated "pretangle" tau (pTau) in the locus coeruleus (LC), the brain's primary source of norepinephrine (NE). While clinical studies link LC pTau burden to behavioral abnormalities, mechanisms underlying these phenomena remain unclear. We developed a translationally-relevant mouse model that recapitulates the 'LC-first' pattern using cell type-specific viral expression of pathogenic P364S mutant human tau in LC neurons. Three months post-infusion, pTau accumulation induced anxiety- and compulsive-like behaviors and reduced sleep spindles without altering overall sleep architecture. Consistent with the behavioral phenotypes, electrophysiological recordings revealed significant increases in spontaneous and evoked firing of LC neurons, accompanied by robust astrocytic reactivity with no apparent cell death. Transcriptomic analysis identified upregulation of Hcn2 and downregulation of Clic6, suggesting changes in neuronal excitability. To further define molecular mechanisms, we developed a cell type-specific proteomics approach, which showed synaptic and metabolic alterations associated with LC-specific tau pathology. While pTau burden persisted at 6 and 9 months after viral infusion, the anxiety-like behaviors observed at 3 months abated at these later timepoints. These findings demonstrate that pTau triggers phenotypes reflective of LC-NE hyperactivity in the early stages of AD pathogenesis, with implications for future noradrenergic-based interventions to address neuropsychiatric manifestations. - Source: PubMed
Publication date: 2026/09/01
Korukonda AnuBlankenship Harris EKam KoreyKour DilpreetEspinosa-Garcia ClaudiaJang Wooyoung EricSrivastava UpasnaMulvey BernardTish Margaret MWitztum RonitRamelow Christina CPate Brittany SLiles L CameronLu LinyueAtallah JakeGuo EugeneMartinowich KeriSharpe Amanda LVarga Andrew WRangaraju SrikantBeckstead Michael JWeinshenker David - Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels are important regulators of cardiac pacemaking and neuronal excitability, yet their temperature dependence has not been compared systematically across mammalian isoforms and species in standardized experimental conditions. Here, we performed a standardized electrophysiological characterization of mouse, rat and human HCN isoforms using stable CHO cell lines and automated patch-clamp recordings across multiple temperatures and pharmacological conditions. Among the four isoforms, HCN3 did not generate detectable currents when expressed as a homomeric channel in the conditions tested, suggesting that additional factors might be required for functional activity. Comparative analysis of the remaining isoforms revealed a conserved kinetic hierarchy, with HCN1 exhibiting the fastest activation kinetics, HCN2 intermediate kinetics and HCN4 the slowest, and temperature accelerated channel gating across isoforms. Canonical modulation by cAMP and ZD7288 further showed that key regulatory features of HCN channels could be quantified reproducibly in identical experimental conditions. Together, these results provide a standardized comparative framework for interpreting HCN channel behaviour across physiological temperatures and species and establish a public reference dataset for future experimental and computational studies. - Source: PubMed
Publication date: 2026/08/30
Ranjan RajnishLogette EmmanuelleHerzog MirjiaBuchillier ValerieScantamburlo EnricoMarkram Henry - The invention in this patent application relates to 1-indazole derivatives represented herein by formula 1. These compounds are inhibitors of hyperpolarization activated cyclic-nucleotide (HCN) modulated ion channel activity, with a selectivity for the inhibition of HCN1/HCN2 isoforms over the HCN4 isoform. The compounds may provide methods for treating, inhibiting, or ameliorating inflammatory and/or neuropathic pain, CNS disorders, psychiatric disorders, mood disorders, and tinnitus. - Source: PubMed
Publication date: 2026/06/23
Abdel-Magid Ahmed F - Gut microbiota-derived short-chain fatty acids (SCFAs) exert critical regulatory functions in inflammatory bowel disease (IBD). However, integrated profiling of fecal SCFA signatures alongside gut microbiota composition in ulcerative colitis (UC) and Crohn's disease (CD) remains insufficiently characterized. Furthermore, the molecular mechanisms through which microbiota metabolites engage host protein targets warrant systematic investigation. - Source: PubMed
Publication date: 2026/06/23
Zhang MenghuiJiang JingjingYang BoZhao WenzhuoZhang JialingMa TianhengWang Honggang