ArticleProceedings of the National Academy of Sciences of the United States of America2016
G protein-gated IKACh channels as therapeutic targets for treatment of sick sinus syndrome and heart block.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 55 citations in OpenAlex.
- The p.Arg52Leu variant in GNB2 causes a gain-of-function due to an increase of IBMC cardiovascular disorders · 2026Article
- L-Type CaCirculation research · 2026Article
- Cardiac automaticity is modulated by IKACh in sinoatrial node during pregnancy.Cardiovascular research · 2024Article
- State-of-the-Art Differentiation Protocols for Patient-Derived Cardiac Pacemaker Cells.International journal of molecular sciences · 2024Review
- Selective blockade of CaNature communications · 2024Article
- Mitochondrial dysfunction is a key link involved in the pathogenesis of sick sinus syndrome: a review.Frontiers in cardiovascular medicine · 2024Review
- Intracardiac electrophysiology to characterize susceptibility to ventricular arrhythmias in murine models.Frontiers in physiology · 2024Article
- Relevance ofInternational journal of molecular sciences · 2023Review
- Genetics of sinoatrial node function and heart rate disorders.Disease models & mechanisms · 2023Review
- Characterization of sinoatrial automaticity in Microcebus murinus to study the effect of aging on cardiac activity and the correlation with longevity.Scientific reports · 2023Article
- Heart rate reduction after genetic ablation of L-type CaFrontiers in cardiovascular medicine · 2023Article
- Pathophysiology of CaFrontiers in physiology · 2023Review
- Atrioventricular node dysfunction in pressure overload-induced heart failure-Involvement of the immune system and transcriptomic remodelling.Frontiers in pharmacology · 2023Article
- Propofol, an Anesthetic Agent, Inhibits HCN Channels through the Allosteric Modulation of the cAMP-Dependent Gating Mechanism.Biomolecules · 2022Article
- Editorial: Cardiac Pacemaking in Health and Disease: From Genes to Function.Frontiers in physiology · 2022Article
- Characterization of VU0468554, a New Selective Inhibitor of Cardiac G Protein-Gated Inwardly Rectifying KMolecular pharmacology · 2021Article
- Implementing Biological Pacemakers: Design Criteria for Successful.Circulation. Arrhythmia and electrophysiology · 2021Review
- RNAseq shows an all-pervasive day-night rhythm in the transcriptome of the pacemaker of the heart.Scientific reports · 2021Article
- Pharmacologic Approach to Sinoatrial Node Dysfunction.Annual review of pharmacology and toxicology · 2021Review
- Genetic Complexity of Sinoatrial Node Dysfunction.Frontiers in genetics · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 7 institutions in 2 countries.
Funding
Abstract
Dysfunction of pacemaker activity in the sinoatrial node (SAN) underlies "sick sinus" syndrome (SSS), a common clinical condition characterized by abnormally low heart rate (bradycardia). If untreated, SSS carries potentially life-threatening symptoms, such as syncope and end-stage organ hypoperfusion. The only currently available therapy for SSS consists of electronic pacemaker implantation. Mice lacking L-type Cav1.3 Ca(2+) channels (Cav1.3(-/-)) recapitulate several symptoms of SSS in humans, including bradycardia and atrioventricular (AV) dysfunction (heart block). Here, we tested whether genetic ablation or pharmacological inhibition of the muscarinic-gated K(+) channel (IKACh) could rescue SSS and heart block in Cav1.3(-/-) mice. We found that genetic inactivation of IKACh abolished SSS symptoms in Cav1.3(-/-) mice without reducing the relative degree of heart rate regulation. Rescuing of SAN and AV dysfunction could be obtained also by pharmacological inhibition of IKACh either in Cav1.3(-/-) mice or following selective inhibition of Cav1.3-mediated L-type Ca(2+) (ICa,L) current in vivo. Ablation of IKACh prevented dysfunction of SAN pacemaker activity by allowing net inward current to flow during the diastolic depolarization phase under cholinergic activation. Our data suggest that patients affected by SSS and heart block may benefit from IKACh suppression achieved by gene therapy or selective pharmacological inhibition.
Indexed as
Identifiers
What OpenQuestion holds
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.