ReviewInternational journal of molecular sciences2015
Pacemaker activity of the human sinoatrial node: an update on the effects of mutations in HCN4 on the hyperpolarization-activated current.
Review in International journal of molecular sciences, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 107 citations in OpenAlex.
- The role of protein palmitoylation in disease pathogenesis and therapeutic innovation.Annals of medicine · 2026Review
- Phenotypic Effects of a Novel HCN4 c.1494C>A (p.Ser498Arg) Sequence Variation.JACC. Case reports · 2026Article
- Aberrant TMPRSS6-Protease Regulation of Disease Mutant HCN4-KCNE1 Channel Complex Depends on the KCNE1-G38S Polymorphism.Archiv der Pharmazie · 2026Article
- Extracellular salt bridge networks around S4 implicated in HCN channel gating and heart disease.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Combination of Autodisplay and Dynamic Pharmacophore Modeling Reveals New Insights into Cyclic Nucleotide Binding in Hyperpolarization-Activated and Cyclic Nucleotide-Gated Ion Channel 4 (HCN4).ACS pharmacology & translational science · 2024Article
- Evaluation of the Potential Targets of Shenxian-Shengmai Oral Liquid in Treating Sick Sinus Syndrome Based on Network Pharmacology and Molecular Docking.Food science & nutrition · 2024Article
- Mitochondrial dysfunction is a key link involved in the pathogenesis of sick sinus syndrome: a review.Frontiers in cardiovascular medicine · 2024Review
- A gain-of-function HCN4 mutant in the HCN domain is responsible for inappropriate sinus tachycardia in a Spanish family.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- An anchor-tether 'hindered' HCN1 inhibitor is antihyperalgesic in a rat spared nerve injury neuropathic pain model.British journal of anaesthesia · 2023Article
- Article
- Local tissue mechanics control cardiac pacemaker cell embryonic patterning.Life science alliance · 2023Article
- Human Sinoatrial Node Pacemaker Activity: Role of the Slow Component of the Delayed Rectifier KInternational journal of molecular sciences · 2023Article
- Palmitoylation regulates the magnitude of HCN4-mediated currents in mammalian cells.Frontiers in physiology · 2023Article
- Article
- Aging-induced atrial fibrosis in IAnnals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2022Article
- Frequency-Dependent Properties of the Hyperpolarization-Activated Cation Current, IInternational journal of molecular sciences · 2022Article
- Altered cyclic nucleotide binding and pore opening in a diseased human HCN4 channel.Biophysical journal · 2022Article
- When Is a Potassium Channel Not a Potassium Channel?Function (Oxford, England) · 2022Article
- Two HCN4 Channels Play Functional Roles in the Zebrafish Heart.Frontiers in physiology · 2022Article
- Review: HCN Channels in the Heart.Current cardiology reviews · 2022Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Since 2003, several loss-of-function mutations in the HCN4 gene, which encodes the HCN4 protein, have been associated with sinus node dysfunction. In human sinoatrial node (SAN), HCN4 is the most abundant of the four isoforms of the HCN family. Tetramers of HCN subunits constitute the ion channels that conduct the hyperpolarization-activated "funny" current (If), which plays an important modulating role in SAN pacemaker activity. Voltage-clamp experiments on HCN4 channels expressed in COS-7, CHO and HEK-293 cells, as well as in Xenopus oocytes have revealed changes in the expression and kinetics of mutant channels, but the extent to which especially the kinetic changes would affect If flowing during a human SAN action potential often remains unresolved. In our contribution to the Topical Collection on Human Single Nucleotide Polymorphisms and Disease Diagnostics, we provide an updated review of the mutation-induced changes in the expression and kinetics of HCN4 channels and provide an overview of their effects on If during the time course of a human SAN action potential, as assessed in simulated action potential clamp experiments. Future research may solve apparent inconsistencies between data from clinical studies and data from in vitro and in silico experiments.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.