ArticleFrontiers in physiology2015
Cholesterol removal from adult skeletal muscle impairs excitation-contraction coupling and aging reduces caveolin-3 and alters the expression of other triadic proteins.
Article in Frontiers in physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Revisiting hypocholesterolemia during prolonged sepsis: From targeted cholesterol repletion to unresolved adrenal and muscle dysfunction.Molecular and cellular endocrinology · 2026Article
- Cholesterol-depleting dextrin depolarizes sarcolemma: the contribution of sodium / calcium channels and membrane integrity.Pflugers Archiv : European journal of physiology · 2026Article
- Skeletal Muscle Mass Modifies the Prognostic Impact of LDL Cholesterol in Chronic Heart Failure.Journal of cachexia, sarcopenia and muscle · 2026Article
- Dysregulation of muscle cholesterol transport in amyotrophic lateral sclerosis.Brain : a journal of neurology · 2025Article
- Effects of membrane cholesterol-targeting chemicals on skeletal muscle contractions evoked by direct and indirect stimulation.Journal of muscle research and cell motility · 2024Article
- Inflammation and Fatty Infiltration Correlates with Rotator Cuff Muscle Atrophy in Hypercholesterolemic Yucatan Microswine.Journal of orthopaedics and sports medicine · 2024Article
- Cholesterol: An Important Determinant of Muscle Atrophy in Astronauts.Journal of biotechnology and biomedicine · 2023Article
- Review
- Centronuclear Myopathy Caused by Defective Membrane Remodelling of Dynamin 2 and BIN1 Variants.International journal of molecular sciences · 2022Review
- Altered cholesterol homeostasis in critical illness-induced muscle weakness: effect of exogenous 3-hydroxybutyrate.Critical care (London, England) · 2021Article
- Article
- Membrane Cholesterol in Skeletal Muscle: A Novel Player in Excitation-Contraction Coupling and Insulin Resistance.Journal of diabetes research · 2017Review
- Age-related alterations in the sarcolemmal environment are attenuated by lifelong caloric restriction and voluntary exercise.Experimental gerontology · 2016Article
- Sarcolemmal dependence of cardiac protection and stress-resistance: roles in aged or diseased hearts.British journal of pharmacology · 2016Review
- Effects of Age on Na(+),K(+)-ATPase Expression in Human and Rodent Skeletal Muscle.Frontiers in physiology · 2016Review
- Association Between Blood Lipid Levels and Lower Extremity Deep Venous Thrombosis: A Population-Based Cohort Study.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/HemostasisArticle
- The Underlying Mechanisms of Diabetic Myopathy.Journal of diabetes researchArticle
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cholesterol and caveolin are integral membrane components that modulate the function/location of many cellular proteins. Skeletal muscle fibers, which have unusually high cholesterol levels in transverse tubules, express the caveolin-3 isoform but its association with transverse tubules remains contentious. Cholesterol removal impairs excitation-contraction (E-C) coupling in amphibian and mammalian fetal skeletal muscle fibers. Here, we show that treating single muscle fibers from adult mice with the cholesterol removing agent methyl-β-cyclodextrin decreased fiber cholesterol by 26%, altered the location pattern of caveolin-3 and of the voltage dependent calcium channel Cav1.1, and suppressed or reduced electrically evoked Ca(2+) transients without affecting membrane integrity or causing sarcoplasmic reticulum (SR) calcium depletion. We found that transverse tubules from adult muscle and triad fractions that contain ~10% attached transverse tubules, but not SR membranes, contained caveolin-3 and Cav1.1; both proteins partitioned into detergent-resistant membrane fractions highly enriched in cholesterol. Aging entails significant deterioration of skeletal muscle function. We found that triad fractions from aged rats had similar cholesterol and RyR1 protein levels compared to triads from young rats, but had lower caveolin-3 and glyceraldehyde 3-phosphate dehydrogenase and increased Na(+)/K(+)-ATPase protein levels. Both triad fractions had comparable NADPH oxidase (NOX) activity and protein content of NOX2 subunits (p47(phox) and gp91(phox)), implying that NOX activity does not increase during aging. These findings show that partial cholesterol removal impairs E-C coupling and alters caveolin-3 and Cav1.1 location pattern, and that aging reduces caveolin-3 protein content and modifies the expression of other triadic proteins. We discuss the possible implications of these findings for skeletal muscle function in young and aged animals.
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