Drug pipeline
Full profile accessExplore the programs pursuing this target and their development progress.
- Drug candidates
- Developers
- Development stage
Target intelligence / Profile preview
Hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4)
- Target
- HCN4
- Molecular classification
- Ion channel, Hyperpolarization-activated cyclic nucleotide-gated channel, Pacemaker channel
01
Overview
Hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) is a membrane ion channel predominantly expressed in the sinoatrial node of the heart, where it generates the “funny” current (If), a mixed Na⁺/K⁺ inward current activated by hyperpolarization and directly regulated by intracellular cAMP binding. cAMP increases channel open probability, facilitating diastolic depolarisation and thus heart rate. HCN channels are crucial for cardiac automaticity and are modulated by autonomic neurotransmitters (e.g., adrenaline), contributing to physiological and pharmacological control of heart rate. Mutations in HCN4 cause sinus node dysfunction, bradycardia, and arrhythmia. Ivabradine and similar drugs act as If/HCN channel antagonists for the treatment of cardiovascular diseases.
- Other names
- Funny current channelPacemaker channelIf channelHyperpolarization-activated channelHCN channel
02
Mechanism of action
Blockade of If/HCN channel, leading to decreased pacemaker activity and reduced heart rate (negative chronotropy)
03
Biological functions
Regulation of cardiac rhythm / pacemakingSignal transduction for heart rate controlInitiation of diastolic depolarisation in sinoatrial node myocytesNeuronal excitability and rhythm generation (in the nervous system)
04
Disease associations
Cardiovascular disease (sinus bradycardia, arrhythmias)Neurodegenerative and neurological diseases (modulation of thalamic and neuronal activity)Other (dysautonomia, infertility of heart rate adaptation)
05
Safety considerations
Excessive bradycardia, heart block, and arrhythmia risk from over-inhibitionOff-target effects in neuronal or other excitable tissues
06
Interacting drugs
Ivabradine
1 more in the full profile.
07
Biomarkers
Heart rate (as a direct readout of HCN channel activity for efficacy monitoring)ECG features, particularly in sinoatrial node dysfunction or arrhythmiaMutations in HCN4 gene (for genetic bradycardia/arrhythmia)
Beyond the preview
Go deeper on Hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4).
Explore the evidence, development activity, and competitive landscape with Gosset’s full data platform.
Clinical trials
Full profile accessFollow the clinical studies evaluating therapies directed at this target.
- Trial design
- Status
- Readouts
Competitive landscape
Full profile accessCompare approaches across drug candidates, modalities, and indications.
- Programs
- Modalities
- Indications
Literature & evidence
Full profile accessInvestigate the research and source evidence behind target biology and development.
- Publications
- Sources
- Analysis
Patents
Full profile accessExplore patent activity around therapies and technologies addressing this target.
- Patents
- Assignees
- Technologies
Research & analysis
Full profile accessConnect target biology, drug development, and emerging evidence in your research.
- Biology
- Development news
- Analysis
Bring the full picture into focus.
See how Gosset can support your research on Hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4).