ArticleBritish journal of pharmacology2018
Simvastatin activates single skeletal RyR1 channels but exerts more complex regulation of the cardiac RyR2 isoform.
Article in British journal of pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- Structural basis for simvastatin-induced skeletal muscle weakness associated with type 1 ryanodine receptor T4709M mutation.The Journal of clinical investigation · 2025Article
- Cryo-electron microscopy reveals sequential binding and activation of Ryanodine Receptors by statin triplets.Nature communications · 2025Article
- Statins affect human iPSC-derived cardiomyocytes by interfering with mitochondrial function and intracellular acidification.Basic research in cardiology · 2024Article
- Statins and Cardiomyocyte Metabolism, Friend or Foe?Journal of cardiovascular development and disease · 2023Review
- New insights on mode of action of vasorelaxant activity of simvastatin.Inflammopharmacology · 2023Article
- Statin activation of skeletal ryanodine receptors (RyR1) is a class effect but separable from HMG-CoA reductase inhibition.British journal of pharmacology · 2022Article
- Mechanisms Underlying Antiarrhythmic Properties of Cardioprotective Agents Impacting Inflammation and Oxidative Stress.International journal of molecular sciences · 2022Review
- Zebrafish as a Model for the Study of Lipid-Lowering Drug-Induced Myopathies.International journal of molecular sciences · 2021Review
- Statin-Induced Myopathy: Translational Studies from Preclinical to Clinical Evidence.International journal of molecular sciences · 2021Review
- Simvastatin protects heart function and myocardial energy metabolism in pulmonary arterial hypertension induced right heart failure.Journal of bioenergetics and biomembranes · 2021Article
- Impact of statin intake on malignant hyperthermia: an in vitro and in vivo swine study.BMC anesthesiology · 2020Article
- A Mechanism for Statin-Induced Susceptibility to Myopathy.JACC. Basic to translational science · 2019Article
- The protective effect of simvastatin against ultraviolet B-induced corneal endothelial cell death.Indian journal of ophthalmology · 2018Article
- Simvastatin activates single skeletal RyR1 channels but exerts more complex regulation of the cardiac RyR2 isoform.British journal of pharmacology · 2018Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
background and purposeStatins are amongst the most widely prescribed drugs for those at risk of cardiovascular disease, lowering cholesterol levels by inhibiting 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase. Although effective at preventing cardiovascular disease, statin use is associated with muscle weakness, myopathies and, occasionally, fatal rhabdomyolysis. As simvastatin, a commonly prescribed statin, promotes Ca EXPERIMENTAL APPROACH: RyR1 and RyR2 single-channel behaviour was investigated after incorporation of sheep cardiac or mouse skeletal SR into planar phospholipid bilayers under voltage-clamp conditions. LC-MS was used to monitor the kinetics of interconversion of simvastatin between hydroxy-acid and lactone forms during these experiments. Cardiac and skeletal myocytes were permeabilised to examine simvastatin modulation of SR Ca KEY
resultsHydroxy acid simvastatin (active at HMG-CoA reductase) significantly and reversibly increased RyR1 open probability (Po) and shifted the distribution of Ca CONCLUSION AND IMPLICATIONS: Simvastatin interacts with RyR1 to increase SR Ca
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Registered trials
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