Affinage

HCN1

Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 · UniProt O60741

Length
890 aa
Mass
98.8 kDa
Annotated
2026-04-28
100 papers in source corpus 47 papers cited in narrative 47 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HCN1 is a hyperpolarization-activated, cyclic nucleotide-gated cation channel subunit that conducts the Ih current to regulate neuronal excitability, dendritic integration, synaptic plasticity, cardiac pacemaking, and sensory transduction across diverse cell types. HCN1 forms homomeric or heteromeric channels (with HCN2 or HCN4) distinguished by fast activation kinetics and minimal cAMP sensitivity; it is enriched in distal apical dendrites of cortical and hippocampal pyramidal neurons via TRIP8b isoform-dependent trafficking, where it constrains temporal summation of synaptic inputs, limits LTP at distal inputs, and shapes spatial coding by grid and place cells (PMID:15550252, PMID:11331358, PMID:21555075, PMID:22099465). Surface expression is dynamically regulated by filamin A–mediated dynamin-dependent internalization, Nedd4-2 ubiquitination, a C-terminal di-arginine ER retention signal, and the accessory protein TMEM74, while presynaptic HCN1 suppresses glutamate release by inhibiting Cav3.2 T-type calcium channels at axon terminals (PMID:24403084, PMID:24451387, PMID:25142030, PMID:21358644). De novo missense mutations in HCN1 cause developmental and epileptic encephalopathy, with transmembrane-domain variants converging on a pathogenic voltage-independent cation leak mechanism (PMID:24747641, PMID:37265603).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2000 High

    Establishing HCN1 as a fast-activating, cortically enriched Ih channel subunit resolved which molecular isoform underlies the kinetically rapid Ih observed in neocortical and hippocampal neurons.

    Evidence Combined single-cell RT-PCR and patch-clamp in mouse CNS neurons correlating HCN1 mRNA with fast Ih kinetics; concatenated HCN1/HCN2 heteromeric constructs in Xenopus oocytes

    PMID:10971612 PMID:11133998

    Open questions at the time
    • No structural basis for faster gating kinetics of HCN1 versus HCN2
    • Relative contribution of homomeric versus heteromeric channels in vivo was unclear
  2. 2001 High

    Demonstrating that HCN1 is essentially cAMP-insensitive (~4 mV shift) while HCN2 shows robust cAMP modulation (~17 mV shift), including downstream of GPCR signaling, established that the two major brain isoforms are differentially regulated by neuromodulatory cascades.

    Evidence Cell-free patch-clamp cAMP dose-response in Xenopus oocytes; GPCR co-expression with pharmacological pathway dissection

    PMID:11331358 PMID:11680627

    Open questions at the time
    • Molecular determinants within the CNBD explaining reduced cAMP efficacy at HCN1 not fully resolved
    • Whether intracellular modulators other than cAMP tune HCN1 gating in neurons
  3. 2001 High

    Identification of HCN1/HCN4 as proton-gated channels in taste cells provided the first specific molecular mechanism for sour taste transduction.

    Evidence Patch-clamp in taste cell slices with acid stimulation; in situ hybridization and immunohistochemistry localizing HCN1 to non-gustducin taste cells

    PMID:11675786

    Open questions at the time
    • Later work identified other sour receptors (PKD2L1/OTOP1), raising questions about the relative contribution of HCN1 to sour transduction in vivo
  4. 2002 High

    Quantitative immunogold EM revealing a 60-fold soma-to-distal-dendrite gradient of HCN1 in pyramidal neurons established the subcellular distribution pattern underlying dendritic Ih function, and identification of HCN1 as the homomeric Ih channel in rod photoreceptors extended functional mapping to sensory neurons.

    Evidence Immunogold EM in hippocampal/cortical pyramidal cells; immunocytochemistry plus patch-clamp comparison of native rod Ih with recombinant HCN1

    PMID:12096053 PMID:12389030

    Open questions at the time
    • Mechanism generating the dendritic gradient was unknown
    • Whether the gradient is static or activity-dependent
  5. 2004 High

    HCN1 knockout mice revealed that dendritic Ih constrains LTP selectively at distal perforant-path inputs and limits hippocampal-dependent spatial learning, directly linking the channel to cognitive function and input-specific synaptic plasticity.

    Evidence Global and forebrain-restricted HCN1 KO mice with LTP recordings, Morris water maze, and fear conditioning

    PMID:15550252

    Open questions at the time
    • Cell-type specificity of the learning phenotype not resolved
    • How HCN1 loss-of-function alters network oscillations contributing to memory consolidation
  6. 2004 High

    Discovery that filamin A binds HCN1 (but not HCN2/HCN4) via a specific 22-aa C-terminal region and controls membrane clustering introduced the first identified HCN1-specific regulatory protein interaction.

    Evidence Yeast two-hybrid screen, co-IP from bovine brain, domain deletion mapping, comparison of channel distribution in filamin A-positive versus -negative cells

    PMID:15292205

    Open questions at the time
    • Whether filamin A mediates the dendritic gradient in vivo
    • Structural basis of the isoform-selective interaction
  7. 2006 High

    Demonstrating that loss of dendritic HCN1 lowers the threshold for dendritic calcium spike generation and causes burst firing in cortical pyramidal neurons provided a cellular mechanism linking Ih downregulation to epileptiform activity.

    Evidence Dual soma-dendrite patch-clamp recordings in WAG/Rij epileptic rats with computational modeling

    PMID:17095562

    Open questions at the time
    • Whether HCN1 downregulation is a cause or consequence of seizures in this model
    • Precise molecular mechanism of HCN1 loss in WAG/Rij rats
  8. 2007 High

    Showing that presynaptic HCN1 expression at perforant path terminals is developmentally regulated by activity-dependent axonal transport revealed a dynamic, non-transcriptional mechanism controlling compartment-specific channel distribution.

    Evidence Immunohistochemistry at developmental time points combined with activity-blockade experiments in vitro

    PMID:17460082

    Open questions at the time
    • Motor/adaptor proteins mediating activity-dependent axonal HCN1 transport not identified
    • Whether this mechanism operates in adult neurons under pathological conditions
  9. 2009 High

    Multiple studies converged to show that HCN1 is a direct target of general anesthetics (ketamine, propofol) via the membrane-embedded channel core, that it controls stellate cell membrane oscillation frequency gradients in entorhinal cortex, and that its loss triggers homeostatic upregulation of tonic GABA-A conductance, broadening HCN1's role from a passive leak to an active integrator of neuronal excitability.

    Evidence KO mouse anesthetic sensitivity assays; stellate cell oscillation frequency gradient analysis in HCN1 KO; pharmacological dissection of tonic GABA-A compensation in cortical neurons

    PMID:19158287 PMID:19515931 PMID:20164346

    Open questions at the time
    • Anesthetic binding site on HCN1 not structurally resolved
    • Whether homeostatic GABA-A compensation occurs in all brain regions
    • Whether the entorhinal frequency gradient depends on HCN1 expression level or channel properties
  10. 2011 High

    Mapping two distinct TRIP8b interaction sites on HCN1 (C-linker/CNBD upstream and SNL/TPR downstream) with separable trafficking and gating functions, plus demonstrating that TRIP8b isoforms have opposing effects on dendritic versus axonal HCN1 targeting, resolved the molecular logic of compartment-specific channel localization.

    Evidence Deletion constructs with trafficking/electrophysiology assays; conditional TRIP8b exon-deletion mice with immunohistochemistry

    PMID:21411649 PMID:21555075

    Open questions at the time
    • How TRIP8b isoform expression itself is regulated
    • Whether TRIP8b controls HCN1 in non-neuronal tissues
  11. 2011 High

    Ultrastructural localization of HCN1 to presynaptic active zones and demonstration that presynaptic HCN1 suppresses glutamate release by inhibiting Cav3.2 T-type Ca2+ channels established a presynaptic function independent of postsynaptic dendritic roles.

    Evidence Immunogold EM colocalization of HCN1 and Cav3.2; electrophysiology in HCN1 KO mice with pharmacological dissection

    PMID:21358644

    Open questions at the time
    • Whether HCN1–Cav3.2 interaction is direct or mediated by membrane voltage alone was unresolved at this point
  12. 2012 High

    In vivo recordings in forebrain-specific HCN1 KO mice showed enlarged but more stable place fields in CA1/CA3, linking dendritic HCN1 and upstream grid cell HCN1 to spatial map resolution.

    Evidence Single-unit place cell recordings during spatial navigation in forebrain-specific HCN1 KO mice

    PMID:22099465

    Open questions at the time
    • Relative contribution of grid cell versus CA1 dendritic HCN1 to place field changes
    • Effect on spatial coding during learning versus recall
  13. 2014 High

    Multiple regulatory mechanisms were defined: filamin A drives dynamin-dependent HCN1 internalization, Nedd4-2 ubiquitinates HCN1 to reduce surface expression opposing TRIP8b(1a-4), and a di-arginine ER retention signal limits forward trafficking—collectively establishing a multi-layered trafficking control system.

    Evidence Live imaging of internalization plus dominant-negative FLNa in neurons; co-IP from brain with Nedd4-2 and functional assays in oocytes/HEK293; mutagenesis of ER retention signal in Xenopus photoreceptors and HEK293

    PMID:24403084 PMID:24451387 PMID:25142030

    Open questions at the time
    • How these regulatory pathways are coordinated in vivo
    • Whether the ER retention signal is masked by TRIP8b or other chaperones during dendritic delivery
  14. 2014 High

    De novo HCN1 missense mutations were identified as a cause of epileptic encephalopathy, with functional analysis revealing both gain- and loss-of-function effects on channel gating, establishing HCN1 as a monogenic epilepsy gene.

    Evidence Exome sequencing of epileptic encephalopathy cohort; patch-clamp of mutant HCN1 channels

    PMID:24747641

    Open questions at the time
    • Whether gain- vs. loss-of-function mutations act through the same circuit mechanism
    • Cell-type-specific impact of mutations not determined
  15. 2017 Medium

    Co-immunoprecipitation of HCN1 with Cav3.2 from brain and mapping of the N-terminal interaction provided a physical basis for the previously observed presynaptic HCN1-mediated suppression of T-type calcium currents.

    Evidence Co-IP from mouse brain and co-transfected cells; electrophysiology showing HCN1 reduces Cav3.2 current amplitude and shifts activation

    PMID:28467171

    Open questions at the time
    • No reciprocal regulation of HCN1 by Cav3.2 observed; asymmetry unexplained
    • Whether the interaction occurs at native presynaptic terminals specifically
  16. 2018 High

    Systematic genotype-phenotype analysis with molecular dynamics simulations revealed that severe DEE-causing mutations cluster in transmembrane domains and can block ion permeation (e.g., G391D) or deform the pore in heterotetramers, while milder variants map to terminal regions.

    Evidence Patch-clamp of 12 variants; MD simulation of G391D homo- and heterotetramers; cohort genotype-phenotype correlation

    PMID:30351409

    Open questions at the time
    • Whether dominant-negative pore deformation fully explains heterozygous patient severity
    • No animal model validation of heterotetramer predictions at this stage
  17. 2022 High

    Knock-in mouse models of G391D and M153I recapitulated spontaneous seizures and revealed that gain-of-function mutations cause HCN1 mislocalization (disrupted basket cell terminal targeting) and paradoxical seizure worsening with Na+ channel blockers, suggesting impaired inhibitory neuron function as a circuit-level pathomechanism.

    Evidence Two independent HCN1 knock-in mouse lines with EEG, immunohistochemistry, and pharmacological challenge

    PMID:35972069

    Open questions at the time
    • Whether mislocalization is a direct consequence of mutant channel folding or aberrant trafficking
    • Contribution of excitatory versus inhibitory neuron dysfunction not fully dissected
  18. 2023 High

    Systematic electrophysiological analysis of seven transmembrane-domain DEE variants converged on a shared voltage-independent cation leak current as the common gain-of-function pathogenic mechanism, unifying diverse biophysical perturbations under a single framework.

    Evidence Two-electrode voltage-clamp of seven variants from eleven patients in Xenopus oocytes

    PMID:37265603

    Open questions at the time
    • Whether cation leak can be pharmacologically targeted for therapy
    • Whether this mechanism explains all transmembrane-domain DEE variants or only those tested
    • No demonstration of leak in native neurons or animal models

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include: the structural basis of HCN1's minimal cAMP sensitivity, whether the cation leak identified in DEE variants can be selectively blocked as a therapeutic strategy, how the multiple trafficking regulators (TRIP8b, filamin A, Nedd4-2, TMEM74, ER retention signal) are coordinated in vivo to establish compartment-specific expression, and the cell-type-specific circuit mechanisms through which HCN1 mutations cause epileptic encephalopathy.
  • No selective HCN1 pharmacological modulator available
  • Structural basis of differential cAMP efficacy between HCN1 and HCN2 unresolved
  • Cell-type-specific contribution to DEE pathogenesis not determined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 9 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 5 GO:0005783 endoplasmic reticulum 1 GO:0005829 cytosol 1
Pathway
R-HSA-112316 Neuronal System 5 R-HSA-382551 Transport of small molecules 4 R-HSA-1643685 Disease 3 R-HSA-9709957 Sensory Perception 3 R-HSA-162582 Signal Transduction 2
Partners
CACNA1HFLNAHCN2HCN4NEDD4LPCDH15TMEM74TRIP8B
Complex memberships
HCN1/HCN2 heterotetramerHCN1/HCN4 heterotetramerHCN1/TRIP8b complexHCN1/filamin A complex

Evidence

Reading pass · 47 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 HCN1 protein shows a 60-fold increase in density from soma to distal apical dendritic membranes in hippocampal, subicular, and neocortical layer-5 pyramidal cells, with distal dendritic shafts having 16-fold more HCN1 than proximal dendrites, and higher density in dendritic shafts than spines at equivalent distances from soma. High-resolution immunolocalization with quantitative immunogold electron microscopy Nature neuroscience High 12389030
2001 HCN1 and HCN2 subunits coassemble to form heteromeric channels with properties intermediate between the two homomers; HCN1 activates 5-10x faster than HCN2 and at more positive voltages, and HCN1 shows minimal cAMP-induced activation curve shift (+4 mV) whereas HCN2 shows +17 mV shift; heteromeric channels closely resemble native Ih in CA1 pyramidal neurons. Xenopus oocyte expression, cell-free patch-clamp recordings, cAMP dose-response analysis The Journal of general physiology High 11331358
2000 HCN1 and HCN2 subunits form functional heteromeric channels demonstrated with concatenated cDNA constructs; heteromeric channels activate faster than HCN2 homomers with voltage dependence similar to HCN2 and cAMP sensitivity intermediate between HCN1 and HCN2. Concatenated cDNA constructs expressed in Xenopus oocytes, electrophysiology The Journal of biological chemistry High 11133998
2004 HCN1 channels are a major component of dendritic Ih in hippocampal CA1 pyramidal cells and constrain LTP specifically at distal perforant path inputs (but not proximal Schaffer collateral inputs), thereby limiting spatial learning and memory; forebrain HCN1 knockout enhances LTP at perforant path and augments theta oscillation power. Global and forebrain-restricted HCN1 knockout mice, whole-cell recordings, LTP induction, behavioral testing (Morris water maze, fear conditioning) Cell High 15550252
2003 HCN4 and HCN1 coassemble into heteromeric channels in cardiac sinoatrial node; 4-1 tandem (HCN4-HCN1) channels have activation kinetics approaching native If, though the cAMP sensitivity and activation range differ from native channels, suggesting additional context-dependent mechanisms modulate channel properties in situ. Heterologous expression in HEK293 cells, concatenated tandem constructs, voltage-clamp electrophysiology The Journal of physiology High 12702747
2004 Filamin A interacts specifically with HCN1 (not HCN2 or HCN4) via a 22-amino acid region in the C-terminal domain downstream of the cyclic nucleotide-binding domain; this interaction is verified by co-immunoprecipitation from bovine brain; in filamin A-expressing cells HCN1 channels cluster in hot spots whereas they distribute evenly without filamin A, indicating filamin A regulates membrane localization; filamin A also modulates HCN1 gating kinetics. Yeast two-hybrid, co-immunoprecipitation from brain tissue, deletion mapping of binding domain, comparison of channel distribution and gating in filamin A-positive vs. filamin A-negative cell lines The Journal of biological chemistry High 15292205
2009 HCN1 channel subunits are directly inhibited by ketamine at clinically relevant concentrations in a subunit-specific manner (HCN1-containing channels more sensitive than others); in cortical pyramidal neurons ketamine induces membrane hyperpolarization and enhanced dendritosomatic synaptic coupling in wild-type but not HCN1 KO mice; HCN1 KO mice show reduced sensitivity to ketamine-induced loss-of-righting reflex (hypnosis); propofol similarly inhibits HCN1 and reduces propofol hypnotic sensitivity in HCN1 KO mice, while etomidate does neither. Recombinant channel electrophysiology, whole-cell recordings in cortical pyramidal neurons from WT and HCN1 KO mice, loss-of-righting reflex behavioral assay The Journal of neuroscience High 19158287
2011 HCN1 subunits localize to the active zone of asymmetric presynaptic terminals targeting entorhinal cortical layer III pyramidal neurons; presynaptic HCN channels inhibit glutamate release by suppressing Cav3.2 T-type calcium channel activity; HCN1 and Cav3.2 colocalize at the ultrastructural level by electron microscopy. Electron microscopy immunolocalization, electrophysiology in HCN1 KO and WT mice, pharmacological dissection Nature neuroscience High 21358644
2011 TRIP8b interacts with HCN1 at two distinct C-terminal sites: (1) an upstream site where HCN1 C-linker/cyclic nucleotide-binding domain binds an 80 aa core of TRIP8b, which is necessary and sufficient to inhibit channel opening and mediates downregulation of surface expression; (2) a downstream site where HCN1 C-terminal SNL tripeptide binds the TRIP8b tetratricopeptide repeat domain to stabilize the complex and optimize interaction. Deletion constructs, binding assays, electrophysiology, trafficking assays in transfected cells The Journal of neuroscience High 21411649
2011 Proper distal dendritic targeting of HCN1 in CA1 pyramidal neurons requires TRIP8b; isoform-wide disruption of TRIP8b/HCN1 interaction leads to HCN1 mislocalization throughout the somatodendritic compartment; two remaining isoforms have opposing roles: TRIP8b(1a-4) promotes HCN1 surface expression in dendrites, while TRIP8b(1a) suppresses HCN1 misexpression in axons. Conditional TRIP8b knockout mice with selective exon deletion, immunohistochemistry, electrophysiology Neuron High 21555075
2007 HCN1 channels at presynaptic terminals of the perforant path in immature rats modulate synaptic efficacy; presynaptic HCN1 expression and function disappear with maturation due to altered axonal transport (not reduced expression in entorhinal cortex soma); blocking action potential firing in vitro restores presynaptic HCN1 expression, indicating activity-dependent regulation of axonal transport. Immunohistochemistry at developmental time points, electrophysiology, activity blockade experiments in vitro The Journal of neuroscience High 17460082
2006 Loss of HCN1 expression in apical dendrites of layer 5 cortical pyramidal neurons increases somatodendritic coupling and lowers the frequency threshold for dendritic Ca2+ spike generation by backpropagating action potentials, causing burst firing; computational modeling confirms that dendritic Ih loss recruits Ca2+ channels to amplify dendritic Ca2+ spikes. Dual whole-cell patch recordings from soma and apical dendrites in WAG/Rij rats plus age-matched controls, compartmental computational modeling The Journal of physiology High 17095562
2009 In cortical pyramidal neurons from HCN1 knockout mice, loss of dendritic Ih triggers homeostatic upregulation of GABA-A alpha5 subunit-mediated tonic current that quantitatively compensates for the loss of shunt current to maintain normal baseline sublinear summation of EPSPs. Whole-cell recordings, pharmacology (bicuculline, L-655,708), immunoblotting, computational modeling The Journal of neuroscience High 20164346
2001 HCN1 and HCN4 channels in taste cells are gated by extracellular protons: lowering extracellular pH shifts the activation curve to more positive voltages and flattens it in a dose-dependent manner, providing a molecular mechanism for sour taste transduction; HCN1 and HCN4 are expressed in a subset of taste cells that do not express gustducin. In situ hybridization, immunohistochemistry, patch-clamp electrophysiology in taste cell slices with acid stimulation Nature High 11675786
2009 HCN1 channels are required for rapid and full activation of Ih in entorhinal layer II stellate cells; they dominate resting membrane conductance, suppress low-frequency (<4 Hz) membrane potential oscillations, and control spike afterhyperpolarization recovery during sustained firing. Whole-cell recordings in brain slices from HCN1 knockout and wild-type adult mice The Journal of neuroscience High 18003822
2009 HCN1 knockout flattens the dorsal-ventral gradient of membrane potential oscillation frequency and resonant frequency in medial entorhinal cortex layer II stellate cells, establishing HCN1 as the molecular substrate for the frequency gradient underlying grid cell field size differences. Whole-cell patch recordings in adult HCN1 global KO mice and controls, analysis of oscillation frequency, resonance, sag potential The Journal of neuroscience High 19515931
2007 Propofol inhibits HCN1 channels by preferentially associating with closed-resting and closed-activated states through the membrane-embedded channel core domain; channel gating is best described by models where closed and open states communicate via voltage-independent reactions with no significant equilibrium occupancy of a deactivated open state. Kinetic modeling of HCN1 gating, decoupling of gating from cAMP and internal protons, electrophysiology with propofol application The Journal of physiology High 17569731
2004 HCN2 and HCN1 channels both contribute to pacemaker current in globus pallidus GABAergic neurons; HCN channels (blocked by ZD7288) significantly slow and destabilize autonomous pacemaking; dendritic HCN2/HCN1 channels enable resetting of pacemaking by transient striatal GABAergic input, shown by computational simulation. Whole-cell electrophysiology in tissue slices, single-cell RT-PCR, immunohistochemistry, computational modeling The Journal of neuroscience High 15525777
2002 HCN1 in rabbit rod photoreceptors is localized to the inner segment and cell body; photoreceptor Ih properties (half-activation voltage ~-75 mV, small cAMP shift ~2.3 mV) closely match homomeric HCN1 expressed in HEK293 cells, establishing HCN1 as the molecular basis of homomeric Ih in rods. Immunocytochemistry, patch-clamp electrophysiology of native rods and HCN1-expressing HEK293 cells The Journal of physiology High 12096053
2008 HCN1 knockout in mouse retina prolongs both scotopic and photopic ERG responses without altering scotopic b-wave amplitude, demonstrating that HCN1 in photoreceptors is required for shortening and shaping of light responses in both rod and cone pathways; HCN1 is strongly expressed in rod and cone photoreceptors as well as some bipolar, amacrine and ganglion cells. Immunohistochemistry, patch-clamp recording, electroretinography in HCN1 KO and WT mice The European journal of neuroscience High 19019198
2014 De novo missense mutations in HCN1 cause epileptic encephalopathy; patch-clamp recordings show mutations have striking but divergent effects on Ih currents in homomeric channels including altered voltage dependence, kinetics, and gating, establishing gain- or loss-of-function as the pathogenic mechanism. Exome sequencing, patch-clamp recordings of mutant human HCN1 channels Nature genetics High 24747641
2014 Filamin A (FLNa) promotes dynamin-dependent internalization of HCN1 channels into endosomal compartments in HEK293 cells; this internalization reduces Ih density; in hippocampal neurons, dominant-negative FLNa enhances HCN1 expression, and decoy peptides disrupting HCN1-FLNa interaction abolish punctate HCN1 distribution and augment endogenous Ih and membrane rebound responses. Mutational and pharmacological approaches, live imaging of channel internalization, dominant-negative FLNa expression, decoy peptides, whole-cell patch-clamp The Journal of biological chemistry High 24403084
2015 Nitric oxide (NO) selectively suppresses HCN1-mediated Ih by hyperpolarizing the half-activation voltage and slowing kinetics in superior olivary neurons that express HCN1 (MSO, LSO, SPN), while simultaneously enhancing HCN2-mediated Ih via cGMP-dependent mechanisms in MNTB neurons that express only HCN2; NO suppression of HCN1 is cGMP-independent and absent in HCN1 KO mice. Whole-cell patch-clamp in superior olivary complex slices from WT and HCN1 KO mice, NO donor application, cGMP pathway pharmacology The Journal of physiology High 25605440
2012 HCN1 in cochlear hair cell stereocilia forms a ternary complex with protocadherin 15 CD3 (a tip-link protein) and F-actin-binding filamin A; alternatively, HCN1 interacts with HCN2 in a complex excluding protocadherin 15 CD3; HCN1-specific N-terminal sequence (not conserved in HCN2 or HCN4) mediates the interaction with protocadherin 15 CD3; the HCN1 N-terminal peptide also binds PI(3,4,5)P3 and PI(4,5)P2. Immunoprecipitation from organ of Corti, EM immunogold localization, peptide competition assays, phosphoinositide-binding assays The Journal of biological chemistry High 22948144
2008 HCN1 N-terminus binds protocadherin 15 CD3 C-terminus in a Ca2+-dependent manner (K_D = 5.26×10^-8 M at 61 µM Ca2+, compared to K_D = 2.39×10^-7 M without Ca2+); binding is mediated by amino acids 158-179 of protocadherin 15 CD3; HCN1 N-terminal self-association (for channel formation) is also Ca2+-dependent but favored at lower Ca2+ concentrations, suggesting competition between binding partners in vivo. Yeast two-hybrid, pull-down assays, surface plasmon resonance with Ca2+ titration, deletion mutagenesis The Journal of biological chemistry High 19008224
2014 Nedd4-2 ubiquitin ligase interacts with HCN1 via a PY motif in the HCN1 C-terminus (and an additional ~100 aa region downstream); Nedd4-2 co-expression reduces HCN1 surface expression by 34% in HEK293 cells and reduces h-current amplitude by 85-92% in oocytes through increased ubiquitination; Nedd4-2 opposes the trafficking-promoting effect of TRIP8b(1a-4), and may reduce N-glycosylation of HCN1. Co-immunoprecipitation from rat brain tissue and HEK293 cells, deletion mutagenesis of PY motif, Xenopus oocyte current recordings, HEK293 surface expression assays FASEB journal High 24451387
2014 A di-arginine ER retention signal in the intrinsically disordered region of the HCN1 C-terminus negatively regulates surface expression; deletion of this signal redirects a reporter to the plasma membrane in Xenopus photoreceptors; mutation of the signal in intact HCN1 increases surface expression in HEK293 cells. Transgenic Xenopus laevis photoreceptor reporter assays, deletion constructs, HEK293 surface expression assay Cellular and molecular life sciences High 25142030
2012 TRIP8b-independent mechanisms control HCN1 localization and function at presynaptic cortical terminals; presynaptic HCN channel expression and function is comparable in TRIP8b-null and wild-type mice, while dendritic HCN channels are strongly reduced; kainic acid-induced seizures persistently decrease presynaptic HCN channel function independently of TRIP8b. Electron microscopy, whole-cell electrophysiology in TRIP8b-null and WT mice, kainate seizure model The Journal of neuroscience High 23077068
2017 HCN1 co-immunoprecipitates with Cav3.2 T-type calcium channels from mouse brain and from tsA-201 cells; the HCN1 N-terminus associates with the Cav3.2 N-terminus; HCN1 expression reduces Cav3.2 Ba2+ current amplitude, shifts Cav3.2 activation gating to more depolarized potentials, and alters kinetics; no reciprocal regulation of HCN1 by Cav3.2 was observed. Co-immunoprecipitation from mouse brain and co-transfected cells, whole-cell electrophysiology, N-terminus interaction mapping Channels (Austin, Tex.) Medium 28467171
2013 HCN1 channels expressed in cerebellar Purkinje cells reduce the duration of inhibitory synaptic responses; selective deletion of HCN1 from Purkinje cells impairs late stages of motor learning in vestibulo-ocular reflex and rotarod tests but does not affect responses to excitatory inputs when membrane hyperpolarization is absent. Cell-type-specific HCN1 conditional knockout mice, whole-cell recordings from Purkinje cells, behavioral motor learning assays The Journal of physiology High 24000178
2012 Knockdown of HCN1 in dorsal hippocampal CA1 region increases cellular excitability and reduces Ih, and produces antidepressant- and anxiolytic-like behaviors associated with upregulation of BDNF-mTOR signaling pathways. Lentiviral shRNA knockdown of HCN1 in rat dorsal hippocampal CA1, whole-cell recordings, behavioral tests, BDNF-mTOR pathway biochemistry Neuron High 22884333
2022 Corticosterone reduces dorsal (but not ventral) CA1 neuron excitability and increases HCN1 protein expression, TRIP8b expression, and Ih via glucocorticoid receptor (GR) and PKA (not CaMKII) signaling pathways; chronic social defeat stress causes sustained elevated perisomatic HCN1 expression and Ih in dorsal CA1 neurons associated with social avoidance. Corticosterone bath application with pharmacological inhibitors of GR, PKA, and CaMKII; immunohistochemistry; whole-cell recordings from dorsal and ventral CA1 in stress model mice Molecular psychiatry Medium 35840797
2019 TMEM74 physically interacts with HCN1 and promotes HCN1 surface trafficking in BLA pyramidal neurons; Tmem74 knockout reduces surface HCN1 expression and Ih, increases neuronal excitability, and produces anxiety-like behavior; TMEM74 transmembrane domain 1 is required for its membrane localization and Ih enhancement. Co-immunoprecipitation, surface expression assays, whole-cell recordings in Tmem74 KO mice, viral rescue in BLA, behavioral anxiety assays Molecular psychiatry Medium 30886335
2000 HCN1 mRNA expression in individual neurons strongly correlates with faster Ih activation kinetics; HCN1 mRNA is present in neocortical and hippocampal pyramidal neurons but absent from dopaminergic midbrain and thalamocortical neurons; HCN1 is expressed at least 8-fold higher in cortical than subcortical neurons. Combined patch-clamp and single-cell RT-multiplex PCR in mouse CNS The European journal of neuroscience High 10971612
2013 HCN1 channels in sinoatrial node stabilize the leading pacemaker region; HCN1-deficient mice display congenital sinus node dysfunction with bradycardia, sinus dysrhythmia, prolonged sinoatrial node recovery time, increased sinoatrial conduction time, and recurrent sinus pauses, causing reduced cardiac output; HCN1 colocalizes with HCN4 in sinoatrial node. HCN1 KO mice, whole-cell recordings from isolated sinoatrial node cells, telemetric ECG, echocardiography, in vivo electrophysiology Circulation High 24218458
2015 A missense mutation (A354V) in HCN1 found in tremulous TRM/Rij rats produces a loss-of-function HCN1 channel that fails to conduct hyperpolarization-activated currents in vitro; pharmacological blockade of HCN1 with ZD7288 in vivo evokes kinetic tremors and activates neurons in the inferior olive; inferior olive lesions reduce tremor, establishing inferior olive as a key locus. Positional cloning, in vitro electrophysiology of mutant channels, ZD7288 in vivo injection, inferior olive lesioning PloS one High 25970616
2021 The HCN1 M305L variant (corresponding to M294L in mouse) lacks voltage-dependent activation and deactivation while retaining normal cation selectivity; molecular dynamics simulations identify a sulphur-aromatic interaction between M305 and F389 in the S5 domain that couples voltage sensor movement to pore opening; a single mutant subunit is sufficient to significantly disrupt voltage-dependent activation in heterotetramers. Two-electrode voltage-clamp in Xenopus oocytes with variable stoichiometry co-injection, molecular dynamics simulation, allosteric gating modeling Progress in biophysics and molecular biology High 34298002
2022 Molecular dynamics simulations of HCN1 selectivity filter show only one stable ion binding site (more flexible and dilated than Kv channels), differential ion coordination and hydration compared to Kv and CNG channels; the C358T mutation stabilizes the binding site and improves fit for Li+ coordination. Molecular dynamics simulations of HCN1 channel and C358T mutant Biophysical journal Medium 35474263
2009 HCN1 channels constrain DHPG-induced mGluR-LTD at Schaffer collateral-CA1 synapses via a presynaptic mechanism: ZD7288 block of HCN channels increases glutamate release probability (shown by reduced paired-pulse ratio and MK-801 experiments), and HCN1 KO mice show enhanced DHPG-LTD but not LFS-LTD, indicating input-specific presynaptic HCN1 regulation. Field recordings, paired-pulse ratio analysis, MK-801 occlusion experiments, HCN1 KO mice Learning & memory Medium 19940037
2017 Presynaptic HCN1 channels in a subset of entorhinal cortical synaptic terminals restrict the rate of synaptic vesicle exocytosis; HCN1 loss increases both spontaneous (miniature and spontaneous) and evoked glutamate release as measured by FM1-43 two-photon imaging and electrophysiology in forebrain-specific and global HCN1 KO mice. Two-photon FM1-43 imaging of vesicle exocytosis, whole-cell electrophysiology, forebrain-specific and global HCN1 KO mice Scientific reports High 28071723
2022 The HCN1 G391D knock-in mutation produces pronounced HCN1 protein mislocalization including disrupted targeting to basket cell axon terminals; both G391D and M153I knock-in mice show spontaneous tonic-clonic seizures; Na+ channel antagonists (lamotrigine, phenytoin) paradoxically induce seizures in both lines consistent with impaired inhibitory neuron function; some mutations render HCN1 channels unresponsive to classic antagonists. HCN1 knock-in mouse models, immunohistochemistry, EEG monitoring, pharmacological seizure induction eLife High 35972069
2023 Seven HCN1 pathogenic variants in transmembrane domains associated with severe epileptic encephalopathy all produce a significantly larger instantaneous cation leak current; other biophysical properties (half-activation voltage, kinetics) vary between variants; cation leak is identified as a common pathogenic mechanism for HCN1-DEE. Two-electrode voltage-clamp in Xenopus oocytes for seven variants from eleven patients Brain communications High 37265603
2012 In HCN1 knockout mice, CA1 and CA3 place fields are larger but more stable; the effect is more pronounced in CA1 than CA3, consistent with HCN1's strong expression in CA1 and weaker expression in CA3; CA3 effects likely reflect loss of HCN1 in entorhinal grid cells that provide spatial input. In vivo place cell recordings in forebrain-specific HCN1 KO mice during spatial navigation Neuron High 22099465
2012 TRIP8b specific splice isoforms regulate axonal HCN1 trafficking in entorhinal perforant path: TRIP8b knockout increases axonal HCN1 in adult medial perforant path; mice lacking only the two most abundant isoforms (1a, 1a-4) show normal HCN1 distribution; overexpression of TRIP8b(1a) (not 1a-4) in cultured neurons promotes somatodendritic and reduces axonal HCN1 localization. TRIP8b isoform-specific knockout mice, immunohistochemistry, overexpression in cultured entorhinal neurons PloS one High 22363812
2018 HCN1 missense mutations cluster within or near transmembrane domains in severe epileptic encephalopathy, while milder phenotype variants are in N- and C-terminal regions; functional analysis shows effects ranging from complete loss-of-function to shifts in activation kinetics/voltage dependence; Gly391Asp blocks ion permeation in homotetramers by Asp-complexed cation, while heterotetramers show instantaneous current due to pore deformation, shown by molecular dynamics simulation. Patch-clamp of 12 selected variants, molecular dynamics simulation of G391D homo- and heterotetramers, cohort genotype-phenotype analysis Brain High 30351409
2014 TRIP8b is required for maximal total HCN1 protein expression in retinal neurons; in TRIP8b KO mice, HCN1 is able to traffic to the surface of retinal neurons normally, but total HCN1 protein is dramatically reduced; multiple TRIP8b isoforms (including three in photoreceptors) colocalize with HCN1 in retina. TRIP8b KO mouse immunohistochemistry, Western blotting, isoform expression profiling PloS one Medium 24409334
2001 Receptor activation of Gs- or Gi-coupled receptors (5-HT4a, mu-opioid) upregulates cAMP to modulate HCN2 but not HCN1 currents in oocytes; HCN2 shows increased amplitude, faster activation, slower deactivation, and a ~15 mV depolarizing shift in voltage dependence; HCN1 is insensitive because it has minimal basal cAMP modulation. Xenopus oocyte co-expression of GPCRs with HCN channels, pharmacological dissection of signaling pathway (SQ22536, PKA/PKC inhibitors) Pflugers Archiv High 11680627

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 A behavioral role for dendritic integration: HCN1 channels constrain spatial memory and plasticity at inputs to distal dendrites of CA1 pyramidal neurons. Cell 396 15550252
2002 Polarized and compartment-dependent distribution of HCN1 in pyramidal cell dendrites. Nature neuroscience 367 12389030
2001 Properties of hyperpolarization-activated pacemaker current defined by coassembly of HCN1 and HCN2 subunits and basal modulation by cyclic nucleotide. The Journal of general physiology 336 11331358
2009 HCN1 channel subunits are a molecular substrate for hypnotic actions of ketamine. The Journal of neuroscience : the official journal of the Society for Neuroscience 212 19158287
2003 Heteromeric HCN1-HCN4 channels: a comparison with native pacemaker channels from the rabbit sinoatrial node. The Journal of physiology 178 12702747
2014 De novo mutations in HCN1 cause early infantile epileptic encephalopathy. Nature genetics 177 24747641
2000 Functional heteromerization of HCN1 and HCN2 pacemaker channels. The Journal of biological chemistry 175 11133998
2001 Hyperpolarization-activated channels HCN1 and HCN4 mediate responses to sour stimuli. Nature 172 11675786
2007 HCN1 channels control resting and active integrative properties of stellate cells from layer II of the entorhinal cortex. The Journal of neuroscience : the official journal of the Society for Neuroscience 152 18003822
2009 Loss of dendritic HCN1 subunits enhances cortical excitability and epileptogenesis. The Journal of neuroscience : the official journal of the Society for Neuroscience 150 19726656
2004 HCN2 and HCN1 channels govern the regularity of autonomous pacemaking and synaptic resetting in globus pallidus neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 144 15525777
2011 Presynaptic HCN1 channels regulate Cav3.2 activity and neurotransmission at select cortical synapses. Nature neuroscience 139 21358644
2006 Inherited cortical HCN1 channel loss amplifies dendritic calcium electrogenesis and burst firing in a rat absence epilepsy model. The Journal of physiology 135 17095562
2012 Enhancement of dorsal hippocampal activity by knockdown of HCN1 channels leads to anxiolytic- and antidepressant-like behaviors. Neuron 129 22884333
2000 Single-cell mRNA expression of HCN1 correlates with a fast gating phenotype of hyperpolarization-activated cyclic nucleotide-gated ion channels (Ih) in central neurons. The European journal of neuroscience 111 10971612
2018 HCN1 mutation spectrum: from neonatal epileptic encephalopathy to benign generalized epilepsy and beyond. Brain : a journal of neurology 105 30351409
2009 Knock-out of HCN1 subunit flattens dorsal-ventral frequency gradient of medial entorhinal neurons in adult mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 91 19515931
2004 Interaction of the pacemaker channel HCN1 with filamin A. The Journal of biological chemistry 87 15292205
2013 Sick sinus syndrome in HCN1-deficient mice. Circulation 77 24218458
2010 Increased seizure severity and seizure-related death in mice lacking HCN1 channels. Epilepsia 72 20384728
2011 TRIP8b regulates HCN1 channel trafficking and gating through two distinct C-terminal interaction sites. The Journal of neuroscience : the official journal of the Society for Neuroscience 70 21411649
2012 HCN1 and HCN2 in Rat DRG neurons: levels in nociceptors and non-nociceptors, NT3-dependence and influence of CFA-induced skin inflammation on HCN2 and NT3 expression. PloS one 69 23236374
2007 Localization of HCN1 channels to presynaptic compartments: novel plasticity that may contribute to hippocampal maturation. The Journal of neuroscience : the official journal of the Society for Neuroscience 67 17460082
2013 Forebrain HCN1 channels contribute to hypnotic actions of ketamine. Anesthesiology 63 23377220
2011 TRIP8b splice forms act in concert to regulate the localization and expression of HCN1 channels in CA1 pyramidal neurons. Neuron 63 21555075
2013 HCN1 channels as targets for anesthetic and nonanesthetic propofol analogs in the amelioration of mechanical and thermal hyperalgesia in a mouse model of neuropathic pain. The Journal of pharmacology and experimental therapeutics 61 23549867
2011 Increased size and stability of CA1 and CA3 place fields in HCN1 knockout mice. Neuron 61 22099465
2018 Selective HCN1 block as a strategy to control oxaliplatin-induced neuropathy. Neuropharmacology 58 29339292
2005 Preferential localization of the hyperpolarization-activated cyclic nucleotide-gated cation channel subunit HCN1 in basket cell terminals of the rat cerebellum. The European journal of neuroscience 58 15869503
2010 Homeostatic regulation of synaptic excitability: tonic GABA(A) receptor currents replace I(h) in cortical pyramidal neurons of HCN1 knock-out mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 56 20164346
2007 Mutation analysis of the hyperpolarization-activated cyclic nucleotide-gated channels HCN1 and HCN2 in idiopathic generalized epilepsy. Neurobiology of disease 53 17931874
2002 Functional characterisation and subcellular localisation of HCN1 channels in rabbit retinal rod photoreceptors. The Journal of physiology 53 12096053
2018 Selective Blockade of HCN1/HCN2 Channels as a Potential Pharmacological Strategy Against Pain. Frontiers in pharmacology 50 30467478
2008 Light responses in the mouse retina are prolonged upon targeted deletion of the HCN1 channel gene. The European journal of neuroscience 49 19019198
2008 In the ventral cochlear nucleus Kv1.1 and subunits of HCN1 are colocalized at surfaces of neurons that have low-voltage-activated and hyperpolarization-activated conductances. Neuroscience 47 18424000
2004 Characterization of the human HCN1 channel and its inhibition by capsazepine. British journal of pharmacology 46 15351778
2020 The potential role of the HCN1 ion channel and BDNF-mTOR signaling pathways and synaptic transmission in the alleviation of PTSD. Translational psychiatry 44 32198387
2018 A novel de novo HCN1 loss-of-function mutation in genetic generalized epilepsy causing increased neuronal excitability. Neurobiology of disease 43 29936235
2006 HCN1 ion channel immunoreactivity in spinal cord and medulla oblongata. Brain research 43 16503331
2018 Applying ketamine to alleviate the PTSD-like effects by regulating the HCN1-related BDNF. Progress in neuro-psychopharmacology & biological psychiatry 39 29596995
2014 Activation of GABAB receptors ameliorates cognitive impairment via restoring the balance of HCN1/HCN2 surface expression in the hippocampal CA1 area in rats with chronic cerebral hypoperfusion. Molecular neurobiology 39 24838625
2015 HCN1 Channels Contribute to the Effects of Amnesia and Hypnosis but not Immobility of Volatile Anesthetics. Anesthesia and analgesia 37 26287296
2003 Cell type-dependent expression of HCN1 in the main olfactory bulb. The European journal of neuroscience 36 12887416
2007 Propofol inhibits HCN1 pacemaker channels by selective association with the closed states of the membrane embedded channel core. The Journal of physiology 33 17569731
2012 TRIP8b-independent trafficking and plasticity of adult cortical presynaptic HCN1 channels. The Journal of neuroscience : the official journal of the Society for Neuroscience 31 23077068
2022 Glucocorticoid-glucocorticoid receptor-HCN1 channels reduce neuronal excitability in dorsal hippocampal CA1 neurons. Molecular psychiatry 28 35840797
2021 Effect of ketamine on mood dysfunction and spatial cognition deficits in PTSD mouse models via HCN1-BDNF signaling. Journal of affective disorders 28 33752039
2014 Filamin A promotes dynamin-dependent internalization of hyperpolarization-activated cyclic nucleotide-gated type 1 (HCN1) channels and restricts Ih in hippocampal neurons. The Journal of biological chemistry 28 24403084
2012 HCN1 and HCN2 proteins are expressed in cochlear hair cells: HCN1 can form a ternary complex with protocadherin 15 CD3 and F-actin-binding filamin A or can interact with HCN2. The Journal of biological chemistry 27 22948144
2015 Nitric oxide selectively suppresses IH currents mediated by HCN1-containing channels. The Journal of physiology 26 25605440
2015 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. Neurobiology of learning and memory 26 26021557
2016 Loss of HCN1 enhances disease progression in mouse models of CNG channel-linked retinitis pigmentosa and achromatopsia. Human molecular genetics 25 26740549
2012 Regulation of axonal HCN1 trafficking in perforant path involves expression of specific TRIP8b isoforms. PloS one 24 22363812
2017 The change of HCN1/HCN2 mRNA expression in peripheral nerve after chronic constriction injury induced neuropathy followed by pulsed electromagnetic field therapy. Oncotarget 23 27901476
2014 Imbalance of HCN1 and HCN2 expression in hippocampal CA1 area impairs spatial learning and memory in rats with chronic morphine exposure. Progress in neuro-psychopharmacology & biological psychiatry 23 25301101
2018 Loss of HCN1 subunits causes absence epilepsy in rats. Brain research 22 30408474
2015 Hcn1 is a tremorgenic genetic component in a rat model of essential tremor. PloS one 22 25970616
2012 HCN1 channels: a new therapeutic target for depressive disorders? Science signaling 22 23033536
2008 Calcium-dependent binding of HCN1 channel protein to hair cell stereociliary tip link protein protocadherin 15 CD3. The Journal of biological chemistry 21 19008224
2019 Functional coupling of Tmem74 and HCN1 channels regulates anxiety-like behavior in BLA neurons. Molecular psychiatry 20 30886335
2017 HCN1 channels reduce the rate of exocytosis from a subset of cortical synaptic terminals. Scientific reports 20 28071723
2013 HCN1 channels in cerebellar Purkinje cells promote late stages of learning and constrain synaptic inhibition. The Journal of physiology 20 24000178
2012 Elevation in type I interferons inhibits HCN1 and slows cortical neuronal oscillations. Cerebral cortex (New York, N.Y. : 1991) 20 23042740
2017 Cyclophosphamide-induced HCN1 channel upregulation in interstitial Cajal-like cells leads to bladder hyperactivity in mice. Experimental & molecular medicine 18 28428632
2006 Role of Hcn1 and its phosphorylation in fission yeast anaphase-promoting complex/cyclosome function. The Journal of biological chemistry 18 16950791
2022 CREB1 transcription-activated lncRNA PVT1 promotes cardiac fibrosis via miR-145/HCN1 axis. International journal of cardiology 17 35063587
2021 Biophysical analysis of an HCN1 epilepsy variant suggests a critical role for S5 helix Met-305 in voltage sensor to pore domain coupling. Progress in biophysics and molecular biology 17 34298002
2003 Morphological analysis of the hyperpolarization-activated cyclic nucleotide-gated cation channel 1 (HCN1) immunoreactive bipolar cells in the rabbit retina. The Journal of comparative neurology 17 14608601
2001 Gi- and Gs-coupled receptors up-regulate the cAMP cascade to modulate HCN2, but not HCN1 pacemaker channels. Pflugers Archiv : European journal of physiology 17 11680627
2013 Spike-and-wave discharge mediated reduction in hippocampal HCN1 channel function associates with learning deficits in a genetic mouse model of epilepsy. Neurobiology of disease 16 24368169
2011 Selective pharmacological inhibition of the pacemaker channel isoforms (HCN1-4) as new possible therapeutical targets. Current medicinal chemistry 16 21774761
2003 Hyperpolarization-activated, cyclic AMP-gated, HCN1-like cation channel: the primary, full-length HCN isoform expressed in a saccular hair-cell layer. Neuroscience 16 12699787
2022 Seizures, behavioral deficits, and adverse drug responses in two new genetic mouse models of HCN1 epileptic encephalopathy. eLife 15 35972069
2020 Cerebral ischemia-reperfusion causes a down regulation of HCN1 expression via enhancing the nuclear NRSF-HDAC4 gathering that contributes to neuron damage. Brain research bulletin 15 31923455
2018 Distal Dendritic Enrichment of HCN1 Channels in Hippocampal CA1 Is Promoted by Estrogen, but Does Not Require Reelin. eNeuro 15 30406178
2022 Novel HCN1 Mutations Associated With Epilepsy and Impacts on Neuronal Excitability. Frontiers in molecular neuroscience 14 35845605
2017 Down-regulation of T-type Cav3.2 channels by hyperpolarization-activated cyclic nucleotide-gated channel 1 (HCN1): Evidence of a signaling complex. Channels (Austin, Tex.) 14 28467171
2014 Nedd4-2 regulates surface expression and may affect N-glycosylation of hyperpolarization-activated cyclic nucleotide-gated (HCN)-1 channels. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 14 24451387
2009 HCN1 channels constrain DHPG-induced LTD at hippocampal Schaffer collateral-CA1 synapses. Learning & memory (Cold Spring Harbor, N.Y.) 14 19940037
1992 Human cortical neuronal cell line (HCN-1): further in vitro characterization and suitability for brain transplantation. Cell transplantation 13 1344290
2015 An N-terminal deletion variant of HCN1 in the epileptic WAG/Rij strain modulates HCN current densities. Frontiers in molecular neuroscience 12 26578877
2013 Genetically-engineered mesenchymal stem cells transfected with human HCN1 gene to create cardiac pacemaker cells. The Journal of international medical research 12 24097828
2009 Activity-dependent regulation of HCN1 protein in cortical neurons. Biochemical and biophysical research communications 11 19563776
2023 Localization of PDE4D, HCN1 channels, and mGluR3 in rhesus macaque entorhinal cortex may confer vulnerability in Alzheimer's disease. Cerebral cortex (New York, N.Y. : 1991) 10 37874022
2014 A di-arginine ER retention signal regulates trafficking of HCN1 channels from the early secretory pathway to the plasma membrane. Cellular and molecular life sciences : CMLS 10 25142030
2016 Use Dependent Attenuation of Rat HCN1-Mediated Ih in Intact HEK293 Cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 9 27184742
2014 TRIP8b is required for maximal expression of HCN1 in the mouse retina. PloS one 9 24409334
2022 Ion behavior in the selectivity filter of HCN1 channels. Biophysical journal 8 35474263
2021 HCN1 channels: A versatile tool for signal processing by primary sensory neurons. Progress in biophysics and molecular biology 8 34197835
2021 Moxibustion Regulates Gastrointestinal Motility via HCN1 in Functional Dyspepsia Rats. Medical science monitor : international medical journal of experimental and clinical research 8 34845181
2015 The expression of hyperpolarization-activated cyclic nucleotide-gated channel 1 (HCN1) and HCN2 in the rat trigeminal ganglion, sensory root, and dental pulp. Neuroscience 8 25659346
2023 Cation leak: a common functional defect causing HCN1 developmental and epileptic encephalopathy. Brain communications 7 37265603
2022 Impaired Color Recognition in HCN1 Epilepsy: A Single Case Report. Frontiers in neurology 7 35359652
2022 Prenatal alcohol exposure enhanced alcohol preference and susceptibility to PTSD in a sex-dependent manner through the synaptic HCN1 channel. Journal of affective disorders 7 36587902
2020 Constitutive Genetic Deletion of Hcn1 Increases Alcohol Preference during Adolescence. Brain sciences 7 33105624
2015 Immunolocalization of hyperpolarization-activated cationic HCN1 and HCN3 channels in the rat nephron: regulation of HCN3 by potassium diets. Histochemistry and cell biology 7 26515056
2010 I(h) "run-up" in rat neocortical neurons and transiently rat or human HCN1-expressing HEK293 cells. Journal of neuroscience research 7 20806410
2023 Retinal Dysfunction in a Mouse Model of HCN1 Genetic Epilepsy. The Journal of neuroscience : the official journal of the Society for Neuroscience 6 36813574
2023 The Impact of Altered HCN1 Expression on Brain Function and Its Relationship with Epileptogenesis. Current neuropharmacology 6 37366350
2022 Evidence for the contribution of HCN1 gene polymorphism (rs1501357) to working memory at both behavioral and neural levels in schizophrenia patients and healthy controls. Schizophrenia (Heidelberg, Germany) 6 35987754