ArticleMolecules (Basel, Switzerland)2012
The "funny" current (I(f)) inhibition by ivabradine at membrane potentials encompassing spontaneous depolarization in pacemaker cells.
Article in Molecules (Basel, Switzerland), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- Intracellular CaInternational journal of molecular sciences · 2026Article
- Pacemaker Channels and the Chronotropic Response in Health and Disease.Circulation research · 2024Review
- Synergy between Membrane Currents Prevents Severe Bradycardia in Mouse Sinoatrial Node Tissue.International journal of molecular sciences · 2023Article
- cAMP-PKA signaling modulates the automaticity of human iPSC-derived cardiomyocytes.The Journal of general physiology · 2023Article
- Improved Generation of Human Induced Pluripotent Stem Cell-Derived Cardiac Pacemaker Cells Using Novel Differentiation Protocols.International journal of molecular sciences · 2022Article
- No evidence for pericardial restraint in the snapping turtle (American journal of physiology. Regulatory, integrative and comparative physiology · 2022Article
- Increase in CaFrontiers in physiology · 2022Article
- Drivers of Sinoatrial Node Automaticity in Zebrafish: Comparison With Mechanisms of Mammalian Pacemaker Function.Frontiers in physiology · 2022Article
- Self-Similar Synchronization of Calcium and Membrane Potential Transitions During Action Potential Cycles Predict Heart Rate Across Species.JACC. Clinical electrophysiology · 2021Article
- The Functional Role of Hyperpolarization Activated Current (Frontiers in physiology · 2021Article
- Novel NaFrontiers in pharmacology · 2019Article
- Positive Feedback Mechanisms among Local Ca Releases, NCX, and IBiophysical journal · 2018Article
- Automatic Optimization of anFrontiers in physiology · 2018Article
- Subtype-specific differentiation of cardiac pacemaker cell clusters from human induced pluripotent stem cells.Stem cell research & therapy · 2017Article
- Electrochemical Na+ and Ca2+ gradients drive coupled-clock regulation of automaticity of isolated rabbit sinoatrial nodal pacemaker cells.American journal of physiology. Heart and circulatory physiology · 2016Article
- Hydroxychloroquine reduces heart rate by modulating the hyperpolarization-activated current If: Novel electrophysiological insights and therapeutic potential.Heart rhythm · 2015Article
- Potential effects of intrinsic heart pacemaker cell mechanisms on dysrhythmic cardiac action potential firing.Frontiers in physiology · 2015Article
- Stochasticity intrinsic to coupled-clock mechanisms underlies beat-to-beat variability of spontaneous action potential firing in sinoatrial node pacemaker cells.Journal of molecular and cellular cardiology · 2014Article
- Modern perspectives on numerical modeling of cardiac pacemaker cell.Journal of pharmacological sciences · 2014Review
- Numerical Modeling Calcium and CaMKII Effects in the SA Node.Frontiers in pharmacology · 2014Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Recent clinical trials have shown that ivabradine (IVA), a drug that inhibits the funny current (I(f)) in isolated sinoatrial nodal cells (SANC), decreases heart rate and reduces morbidity and mortality in patients with cardiovascular diseases. While IVA inhibits I(f), this effect has been reported at essentially unphysiological voltages, i.e., those more negative than the spontaneous diastolic depolarization (DD) between action potentials (APs). We tested the relative potency of IVA to block I(f) over a wide range of membrane potentials, including those that encompass DD governing to the SANC spontaneous firing rate. A clinically relevant IVA concentration of 3 μM to single, isolated rabbit SANC slowed the spontaneous AP firing rate by 15%. During voltage clamp the maximal I(f) was 18 ± 3 pA/pF (at -120 mV) and the maximal I(f) reduction by IVA was 60 ± 8% observed at -92 ± 4 mV. At the maximal diastolic depolarization (~-60 mV) I(f) amplitude was only -2.9 ± 0.4 pA/pF, and was reduced by only 41 ± 6% by IVA. Thus, I(f) amplitude and its inhibition by IVA at physiologically relevant membrane potentials are substantially less than that at unphysiological (hyperpolarized) membrane potentials. This novel finding more accurately describes how IVA affects SANC function and is of direct relevance to numerical modeling of SANC automaticity.
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Registered trials
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.