ArticleThe Journal of biological chemistry2012
Hypercholesterolemia induces up-regulation of KACh cardiac currents via a mechanism independent of phosphatidylinositol 4,5-bisphosphate and Gβγ.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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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.
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Who cites it
18 citing papers in PubMed, 39 citations in OpenAlex.
- The interaction between sarcoplasmic reticulum and mitochondria: a novel mechanism for cardiac arrhythmia.Frontiers in physiology · 2026Review
- Emerging Signaling Regulation of Sinoatrial Node Dysfunction.Current cardiology reports · 2023Review
- PI(4,5)PAdvances in experimental medicine and biology · 2023Article
- From Crosstalk to Synergism: The Combined Effect of Cholesterol and PI(4,5)PAdvances in experimental medicine and biology · 2023Review
- A molecular switch controls the impact of cholesterol on a Kir channel.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Structural and Electrical Remodeling of the Sinoatrial Node in Diabetes: New Dimensions and Perspectives.Frontiers in endocrinology · 2022Review
- Measurement of Single-Molecule Forces in Cholesterol and Cyclodextrin Host-Guest Complexes.The journal of physical chemistry. B · 2021Article
- Upstream Statin Therapy and Long-Term Recurrence of Atrial Fibrillation after Cardioversion: A Propensity-Matched Analysis.Journal of clinical medicine · 2021Article
- Functional marriage in plasma membrane: Critical cholesterol level-optimal protein activity.British journal of pharmacology · 2020Review
- Regulation of interleukin-1 beta secretion from macrophages via modulation of potassium ion (KFEBS letters · 2019Article
- Cholesterol intake and statin use regulate neuronal G protein-gated inwardly rectifying potassium channels.Journal of lipid research · 2019Article
- Cholesterol-Binding Sites in GIRK Channels: The Devil is in the Details.Lipid insights · 2018Article
- Dual activation of neuronal G protein-gated inwardly rectifying potassium (GIRK) channels by cholesterol and alcohol.Scientific reports · 2017Article
- Cholesterol up-regulates neuronal G protein-gated inwardly rectifying potassium (GIRK) channel activity in the hippocampus.The Journal of biological chemistry · 2017Article
- Impact of duration and dosage of statin treatment and epicardial fat thickness on the recurrence of atrial fibrillation after electrical cardioversion.Heart and vessels · 2015Observational
- Cholesterol binding to ion channels.Frontiers in physiology · 2014Review
- Metabolic syndrome remodels electrical activity of the sinoatrial node and produces arrhythmias in rats.PloS one · 2013Article
- Cholesterol sensitivity of KIR2.1 depends on functional inter-links between the N and C termini.Channels (Austin, Tex.)Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Hypercholesterolemia is a well-known risk factor for cardiovascular disease. In the heart, activation of K(ACh) mediates the vagal (parasympathetic) negative chronotropic effect on heart rate. Yet, the effect of cholesterol on K(ACh) is unknown. Here we show that cholesterol plays a critical role in modulating K(ACh) currents (I(K,ACh)) in atrial cardiomyocytes. Specifically, cholesterol enrichment of rabbit atrial cardiomyocytes led to enhanced channel activity while cholesterol depletion suppressed I(K,ACh). Moreover, a high-cholesterol diet resulted in up to 3-fold increase in I(K,ACh) in rodents. In accordance, elevated currents were observed in Xenopus oocytes expressing the Kir3.1/Kir3.4 heteromer that underlies I(K,ACh). Furthermore, our data suggest that cholesterol affects I(K,ACh) via a mechanism which is independent of both PI(4,5)P(2) and Gβγ. Interestingly, the effect of cholesterol on I(K,ACh) is opposite to its effect on I(K1) in atrial myocytes. The latter are suppressed by cholesterol enrichment and by high-cholesterol diet, and facilitated following cholesterol depletion. These findings establish that cholesterol plays a critical role in modulating I(K,ACh) in atrial cardiomyocytes via a mechanism independent of the channel's major modulators.
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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.