ArticleBritish journal of pharmacology2009
Statins and fenofibrate affect skeletal muscle chloride conductance in rats by differently impairing ClC-1 channel regulation and expression.
Article in British journal of pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Is a PCSK9 Inhibitor Right for Your Patient? A Review of Treatment Data for Individualized Therapy.International journal of environmental research and public health · 2022Pooled it
- Myotonia: Recognition, Evaluation, and Differential Diagnosis.Muscle & nerve · 2026Review
- Hypertriglyceridemia Therapy: Past, Present and Future Perspectives.International journal of molecular sciences · 2024Review
- The Role of Mitochondria in Statin-Induced Myopathy.Drug safety · 2024Review
- Effect of Linoleic Acid on Cholesterol Levels in a High-Fat Diet-Induced Hypercholesterolemia Rat Model.Metabolites · 2022Article
- Article
- Statin-Induced Myopathy: Translational Studies from Preclinical to Clinical Evidence.International journal of molecular sciences · 2021Review
- Skeletal muscle ClC-1 chloride channels in health and diseases.Pflugers Archiv : European journal of physiology · 2020Review
- The marine-derived furanone reduces intracellular lipid accumulation in vitro by targeting LXRα and PPARα.Journal of cellular and molecular medicine · 2020Article
- Defective Gating and Proteostasis of Human ClC-1 Chloride Channel: Molecular Pathophysiology of Myotonia Congenita.Frontiers in neurology · 2020Review
- Elucidating the Contribution of Skeletal Muscle Ion Channels to Amyotrophic Lateral Sclerosis in search of new therapeutic options.Scientific reports · 2019Article
- Simvastatin Enhances Activity and Trafficking of α7 Nicotinic Acetylcholine Receptor in Hippocampal Neurons Through PKC and CaMKII Signaling Pathways.Frontiers in pharmacology · 2018Article
- Risk of Myopathy in Patients in Therapy with Statins: Identification of Biological Markers in a Pilot Study.Frontiers in pharmacology · 2017Article
- Curcumin improves atorvastatin-induced myotoxicity in rats: Histopathological and biochemical evidence.International journal of immunopathology and pharmacology · 2016Article
- Protein kinase C-dependent regulation of ClC-1 channels in active human muscle and its effect on fast and slow gating.The Journal of physiology · 2016Article
- Role of physiological ClC-1 Cl- ion channel regulation for the excitability and function of working skeletal muscle.The Journal of general physiology · 2016Review
- ClC-1 chloride channels: state-of-the-art research and future challenges.Frontiers in cellular neuroscience · 2015Review
- Protein kinase C theta (PKCθ) modulates the ClC-1 chloride channel activity and skeletal muscle phenotype: a biophysical and gene expression study in mouse models lacking the PKCθ.Pflugers Archiv : European journal of physiology · 2014Article
- An olive oil-derived antioxidant mixture ameliorates the age-related decline of skeletal muscle function.Age (Dordrecht, Netherlands) · 2014Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeStatins and fibrates can produce mild to life-threatening skeletal muscle damage. Resting chloride channel conductance (gCl), carried by the ClC-1 channel, is reduced in muscles of rats chronically treated with fluvastatin, atorvastatin or fenofibrate, along with increased resting cytosolic calcium in statin-treated rats. A high gCl, controlled by the Ca(2+)-dependent protein kinase C (PKC), maintains sarcolemma electrical stability and its reduction alters muscle function. Here, we investigated how statins and fenofibrate impaired gCl. EXPERIMENTAL APPROACH: In rats treated with fluvastatin, atorvastatin or fenofibrate, we examined the involvement of PKC in gCl reduction by the two intracellular microelectrodes technique and ClC-1 mRNA level by quantitative real time-polymerase chain reaction. Direct drug effects were tested by patch clamp analysis on human ClC-1 channels expressed in human embryonic kidney (HEK) 293 cells. KEY
resultsChelerythrine, a PKC inhibitor, applied in vitro on muscle dissected from atorvastatin-treated rats fully restored gCl, suggesting the involvement of this enzyme in statin action. Chelerythrine partially restored gCl in muscles from fluvastatin-treated rats but not in those from fenofibrate-treated rats, implying additional mechanisms for gCl impairment. Accordingly, a decrease of ClC-1 channel mRNA was found in both fluvastatin- and fenofibrate-treated rat muscles. Fenofibric acid, the in vivo metabolite of fenofibrate, but not fluvastatin, rapidly reduced chloride currents in HEK 293 cells. CONCLUSIONS AND IMPLICATIONS: Our data suggest multiple mechanisms underlie the effect of statins and fenofibrate on ClC-1 channel conductance. While statins promote Ca(2+)-mediated PKC activation, fenofibrate directly inhibits ClC-1 channels and both fluvastatin and fenofibrate impair expression of mRNA for ClC-1.
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