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Hyperpolarization activated cyclic nucleotide-gated potassium channel 4

This gene encodes a member of the hyperpolarization-activated cyclic nucleotide-gated potassium channels. The encoded protein shows slow kinetics of activation and inactivation, and is necessary for the cardiac pacemaking process. This channel may also mediate responses to sour stimuli. Mutations in this gene have been linked to sick sinus syndrome 2, also known as atrial fibrillation with bradyarrhythmia or familial sinus bradycardia. Two pseudogenes have been identified on chromosome 15. [provided by RefSeq, Oct 2008] (from NCBI)
Top mentioned proteins: HCN2, HCN1, CAN, HAD, NODAL
Papers on HCN4
Current understanding of the pathophysiological mechanisms responsible for inappropriate sinus tachycardia: role of the If "funny" current.
DiFrancesco et al., Milano, Italy. In J Interv Card Electrophysiol, Feb 2016
RESULTS: Recent evidence demonstrates that a familial form of IST is associated with a gain-of-function mutation in the HCN4 pacemaker channel (R524Q) which confers an increased sensitivity to the second messenger cAMP, a key mediator in sympathetic modulation.
Therapeutic effect of astragaloside-IV on bradycardia is involved in up-regulating klotho expression.
Tang et al., China. In Life Sci, Feb 2016
AIMS: In order to determine whether klotho is involved in the therapeutic effects of Astragaloside-IV on bradycardia, we evaluated the effect of ASG-IV on klotho and the effect of klotho on HCN4 and If.
Preserved Autonomic Cardiovascular Regulation With Cardiac Pacemaker Inhibition: A Crossover Trial Using High-Fidelity Cardiovascular Phenotyping.
Jordan et al., Berlin, Germany. In J Am Heart Assoc, Dec 2015
BACKGROUND: Sympathetic and parasympathetic influences on heart rate (HR), which are governed by baroreflex mechanisms, are integrated at the cardiac sinus node through hyperpolarization-activated cyclic nucleotide-gated channels (HCN4).
Genetic Regulation of Sinoatrial Node Development and Pacemaker Program in the Venous Pole.
Chen et al., New Orleans, United States. In J Cardiovasc Dev Dis, Dec 2015
UNASSIGNED: The definitive sinoatrial node (SAN), the primary pacemaker of the mammalian heart, develops from part of pro-pacemaking embryonic venous pole that expresses both Hcn4 and the transcriptional factor Shox2.
Dynamic Expression of Hyperpolarization-activated Cyclic Nucleotide-gated Cation Channel 4 Involved in Microwave Induced Pacemaker Cell Injuries.
Peng et al., Beijing, China. In Biomed Environ Sci, Nov 2015
Moreover, hyperpolarization- activated cyclic nucleotide-gated cation channel 4 (HCN4) was down-regulated immediately after the exposure and up-regulated at 12 h after the exposure.
Building models for postmortem abnormalities in hippocampus of schizophrenics.
Benes, Belmont, United States. In Schizophr Res, Sep 2015
Abnormal expression changes in the expression of kainate receptor (KAR) subunits 5, 6 and 7, as well as an inwardly-rectifying hyperpolarization-activated cationic channel (Ih3; HCN3) may play important roles in regulating GABA cell activity at the SO CA3/2 locus.
[Changes of HCN4, Cx43 Expression in the Sinoatrial Node of Electric Shock Death].
Wang et al., In Fa Yi Xue Za Zhi, Aug 2015
OBJECTIVE: To investigate the expression of hyperpolarization-activated cyclic nucleotide-gated cation channel 4 (HCN4) and connexin43 (Cx43) in the sinoatrial node of electric shock death.
Insights into cardiac conduction system formation provided by HCN4 expression.
Sun et al., Shanghai, China. In Trends Cardiovasc Med, 2015
In this review, we briefly summarize available mouse models of CCS markers and focus on those involving the hyperpolarization cation-selective nucleotide-gated cation channel, HCN4, which selectively marks all components of the specialized CCS in adult heart.
Pacemaker activity of the human sinoatrial node: an update on the effects of mutations in HCN4 on the hyperpolarization-activated current.
Wilders et al., Amsterdam, Netherlands. In Int J Mol Sci, 2014
Since 2003, several loss-of-function mutations in the HCN4 gene, which encodes the HCN4 protein, have been associated with sinus node dysfunction.
Characterization of the role of HCN channels in β3-adrenoceptor mediated rat bladder relaxation.
Tyagi et al., Pittsburgh, United States. In Bladder (san Franc), 2014
Species based differences were evident from relatively higher expression of HCN4 isoform in human bladder and that of HCN1 in rat bladder.
T-type channels in the sino-atrial and atrioventricular pacemaker mechanism.
Mangoni et al., Montpellier, France. In Pflugers Arch, 2014
Strikingly, T-type channel isoforms are co-expressed in the cardiac conduction system with other ion channels that play a major role in pacemaking such as f- (HCN4) and L-type Cav1.3 channels.
Pacemaker activity of the human sinoatrial node: effects of HCN4 mutations on the hyperpolarization-activated current.
Wilders et al., Amsterdam, Netherlands. In Europace, 2014
In human SAN, HCN4 is the most abundant of the four isoforms of the HCN family.
A HCN4+ cardiomyogenic progenitor derived from the first heart field and human pluripotent stem cells.
Chien et al., Boston, United States. In Nat Cell Biol, 2013
Here, we present Hcn4 (hyperpolarization-activated cyclic nucleotide-gated channel 4) as an FHF marker.
Hyperpolarisation-activated cyclic nucleotide channel 4 (HCN4) involvement in Tourette's syndrome autoimmunity.
Shyu et al., Taipei, Taiwan. In J Neuroimmunol, 2012
Anti-HCN4 antibodies in the brain might contribute to the pathogenesis of tic symptoms in Tourette's syndrome patients.
A caveolin-binding domain in the HCN4 channels mediates functional interaction with caveolin proteins.
Difrancesco et al., Milano, Italy. In J Mol Cell Cardiol, 2012
The conserved CBD present in all HCN isoforms mediates their functional interaction with caveolins.
Adrenergic regulation of HCN4 channel requires protein association with β2-adrenergic receptor.
Hoshi et al., Irvine, United States. In J Biol Chem, 2012
Data show that beta(2)-adrenergic receptors beta(2)ARs form protein complexes with the HCN4 channel, as well as with other subtypes of HCN channels.
Thy1 associates with the cation channel subunit HCN4 in adult rat retina.
Ishida et al., Davis, United States. In Invest Ophthalmol Vis Sci, 2012
first report that Thy1 colocalizes and coimmunoprecipitates with a membrane-spanning protein in retina, that Thy1 complexes with an ion channel protein in any tissue, and that a GPI-anchored protein associates with an HCN channel subunit protein (HDN4)
Novel insights into the distribution of cardiac HCN channels: an expression study in the mouse heart.
Ludwig et al., Nürnberg, Germany. In J Mol Cell Cardiol, 2011
HCN4 was confirmed as the predominant isoform of the primary pacemaker.
Familial sinus bradycardia associated with a mutation in the cardiac pacemaker channel.
DiFrancesco et al., Milano, Italy. In N Engl J Med, 2006
Sinus bradycardia in members of a large family was associated with a mutation in the gene coding for the pacemaker HCN4 ion channel.
Hyperpolarization-activated channels HCN1 and HCN4 mediate responses to sour stimuli.
Lindemann et al., Homburg, Germany. In Nature, 2001
The rat HCN1 and HCN4 were shown to mediate responses to sour stimuli, suggesting a potential new function for the related human proteins.
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