ArticleBiophysical journal2004
Interplay of troponin- and Myosin-based pathways of calcium activation in skeletal and cardiac muscle: the use of W7 as an inhibitor of thin filament activation.
Article in Biophysical journal, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- Targeting Troponin C with Small Molecules Containing Diphenyl Moieties: Calcium Sensitivity Effects on Striated Muscles and Structure-Activity Relationship.Journal of chemical information and modeling · 2023Article
- Targeting Troponin C with Small Molecules Containing Diphenyl Moieties: Calcium Sensitivity Effects on Striated Muscle and Structure Activity Relationship.bioRxiv : the preprint server for biology · 2023Article
- Cardiac sarcomere mechanics in health and disease.Biophysical reviews · 2021Review
- A Potent Fluorescent Reversible-Covalent Inhibitor of Cardiac Muscle Contraction.ACS medicinal chemistry letters · 2021Article
- Molecular Mechanisms of the Deregulation of Muscle Contraction Induced by the R90P Mutation in Tpm3.12 and the Weakening of This Effect by BDM and W7.International journal of molecular sciences · 2021Article
- Depletion of Vasohibin 1 Speeds Contraction and Relaxation in Failing Human Cardiomyocytes.Circulation research · 2020Article
- Molecular Mechanisms of Muscle Weakness Associated with E173A Mutation in Tpm3.12. Troponin CaInternational journal of molecular sciences · 2020Article
- Fropofol prevents disease progression in mice with hypertrophic cardiomyopathy.Cardiovascular research · 2020Article
- Omecamtiv Mecarbil Slows Myosin Kinetics in Skinned Rat Myocardium at Physiological Temperature.Biophysical journal · 2019Article
- Regulatory light chain phosphorylation augments length-dependent contraction in PTU-treated rats.The Journal of general physiology · 2019Article
- Effects of cross-bridge compliance on the force-velocity relationship and muscle power output.PloS one · 2017Article
- Sarcomere neutralization in inherited cardiomyopathy: small-molecule proof-of-concept to correct hyper-Ca2+-sensitive myofilaments.American journal of physiology. Heart and circulatory physiology · 2016Article
- Probing the mechanism of cardiovascular drugs using a covalent levosimendan analog.Journal of molecular and cellular cardiology · 2016Article
- Increased Titin Compliance Reduced Length-Dependent Contraction and Slowed Cross-Bridge Kinetics in Skinned Myocardial Strips from Rbm (20ΔRRM) Mice.Frontiers in physiology · 2016Article
- Review
- Targeting the sarcomere to correct muscle function.Nature reviews. Drug discovery · 2015Review
- Targets for therapy in sarcomeric cardiomyopathies.Cardiovascular research · 2015Review
- Solution structure of the regulatory domain of human cardiac troponin C in complex with the switch region of cardiac troponin I and W7: the basis of W7 as an inhibitor of cardiac muscle contraction.Journal of molecular and cellular cardiology · 2010Article
- Solution structure of human cardiac troponin C in complex with the green tea polyphenol, (-)-epigallocatechin 3-gallate.The Journal of biological chemistry · 2009Article
- Structure of the inhibitor W7 bound to the regulatory domain of cardiac troponin C.Biochemistry · 2009Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
To investigate the interplay between the thin and thick filaments during calcium activation in striated muscle, we employed n-(6-aminohexyl) 5-chloro-1-napthalenesulfonamide (W7) as an inhibitor of troponin C and compared its effects with that of the myosin-specific inhibitor, 2,3-butanedione 2-monoxime (BDM). In both skeletal and cardiac fibers, W7 reversibly inhibited ATPase and tension over the full range of calcium activation between pCa 8.0 and 4.5, resulting in reduced calcium sensitivity and cooperativity of ATPase and tension activations. At maximal activation in skeletal fibers, the W7 concentrations for half-maximal inhibition (KI) were 70-80 micro M for ATPase and 20-30 micro M for tension, nearly >200-fold lower than BDM (20 mM and 5-8 mM, respectively). When W7 (50 microM) and BDM (20 mM) were combined in skeletal fibers, the ATPase and tension-pCa curves exhibited lower apparent cooperativity and maxima and higher calcium sensitivity than expected from two independent activation pathways, suggesting that the interplay between the thin and thick filaments varies with the level of activation. Significantly, the inhibition of W7 increased the ATPase/tension ratio during activation in both muscle types. W7 holds much promise as a potent and reversible inhibitor of thin filament-mediated calcium activation of skeletal and cardiac muscle contraction.
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