ArticleThe Journal of general physiology2002
Current-dependent block of rabbit sino-atrial node I(f) channels by ivabradine.
Article in The Journal of general physiology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.
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Who cites it
104 citing papers in PubMed, 283 citations in OpenAlex.
- Cardiac pacemaker channel (HCN4) inhibition and atrial arrhythmogenesis after releasing cardiac sympathetic activation.Scientific reports · 2018Trial
- Preserved Autonomic Cardiovascular Regulation With Cardiac Pacemaker Inhibition: A Crossover Trial Using High-Fidelity Cardiovascular Phenotyping.Journal of the American Heart Association · 2016Trial
- Heart rate at baseline influences the effect of ivabradine on cardiovascular outcomes in chronic heart failure: analysis from the SHIFT study.Clinical research in cardiology : official journal of the German Cardiac Society · 2013Trial
- Pharmacodynamic effects of ivabradine, a negative chronotropic agent, in healthy cats.Journal of veterinary cardiology : the official journal of the European Society of Veterinary Cardiology · 2011Trial
- Trial
- Comparative effects of ivabradine, a selective heart rate-lowering agent, and propranolol on systemic and cardiac haemodynamics at rest and during exercise.British journal of clinical pharmacology · 2006Trial
- Aglianico Grape Pomace Extract Reduces Cardiac Pacemaker Activity by Decreasing Hyperpolarization-Activated Current Density Independently of cAMP Signaling.Life (Basel, Switzerland) · 2026Article
- Structure mirroring function: What's the 'matter' with the funny current?The Journal of physiology · 2026Review
- Achieved targeted heart rate following ivabradine therapy correlates with left ventricular reverse remodeling in non-ischemic dilated cardiomyopathy.Scientific reports · 2025Article
- Cardiovascular manifestations in mast cell activation disease: key insights for cardiologists and angiologists.Frontiers in cardiovascular medicine · 2025Review
- Article
- Structural determinants of ivabradine block of the open pore of HCN4.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Pacemaker Channels and the Chronotropic Response in Health and Disease.Circulation research · 2024Review
- Inhibition of HCN1 currents by norquetiapine, an active metabolite of the atypical anti-psychotic drug quetiapine.Frontiers in pharmacology · 2024Article
- Predictors of Cardiac Autonomic Dysfunction in Obesity-Related Hypertension.High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension · 2024Article
- Pharmacotherapy in patients with vasomotor disorders.International journal of cardiology. Heart & vasculature · 2023Review
- The funny current If is essential for the fight-or-flight response in cardiac pacemaker cells.The Journal of general physiology · 2022Article
- Article
- Frequency-Dependent Properties of the Hyperpolarization-Activated Cation Current, IInternational journal of molecular sciences · 2022Article
- Article
44 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
"Funny" (f-) channels have a key role in generation of spontaneous activity of pacemaker cells and mediate autonomic control of cardiac rate; f-channels and the related neuronal h-channels are composed of hyperpolarization-activated, cyclic nucleotide-gated (HCN) channel subunits. We have investigated the block of f-channels of rabbit cardiac sino-atrial node cells by ivabradine, a novel heart rate-reducing agent. Ivabradine is an open-channel blocker; however, block is exerted preferentially when channels deactivate on depolarization, and is relieved by long hyperpolarizing steps. These features give rise to use-dependent behavior. In this, the action of ivabradine on f-channels is similar to that reported of other rate-reducing agents such as UL-FS49 and ZD7288. However, other features of ivabradine-induced block are peculiar and do not comply with the hypothesis that the voltage-dependence of block is entirely attributable to either the sensitivity of ivabradine-charged molecules to the electrical field in the channel pore, or to differential affinity to different channel states, as has been proposed for UL-FS49 (DiFrancesco, D. 1994. Pflugers Arch. 427:64-70) and ZD7288 (Shin, S.K., B.S. Rotheberg, and G. Yellen. 2001. J. Gen. Physiol. 117:91-101), respectively. Experiments where current flows through channels is modified without changing membrane voltage reveal that the ivabradine block depends on the current driving force, rather than voltage alone, a feature typical of block induced in inwardly rectifying K(+) channels by intracellular cations. Bound drug molecules do not detach from the binding site in the absence of inward current through channels, even if channels are open and the drug is therefore not "trapped" by closed gates. Our data suggest that permeation through f-channel pores occurs according to a multiion, single-file mechanism, and that block/unblock by ivabradine is coupled to ionic flow. The use-dependence resulting from specific features of I(f) block by ivabradine amplifies its rate-reducing ability at high spontaneous rates and may be useful to clinical applications.
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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.