ArticleBiophysical journal2007
Kinetic mechanism of the Ca2+-dependent switch-on and switch-off of cardiac troponin in myofibrils.
Article in Biophysical journal, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- Direct measurement of mavacamten and deoxyATP perturbation of the SRX/DRX ratio in porcine cardiac myofibrils using a simple, accessible and multiplexed approach.Journal of muscle research and cell motility · 2025Article
- Assessing Cardiac Contractility From Single Molecules to Whole Hearts.JACC. Basic to translational science · 2024Review
- The relation between sarcomere energetics and the rate of isometric tension relaxation in healthy and diseased cardiac muscle.Journal of muscle research and cell motility · 2021Article
- Hypertrophic and Dilated Cardiomyopathy-Associated Troponin T Mutations R130C and ΔK210 Oppositely Affect Length-Dependent Calcium Sensitivity of Force Generation.Frontiers in physiology · 2020Article
- Cycling Cross-Bridges Contribute to Thin Filament Activation in Human Slow-Twitch Fibers.Frontiers in physiology · 2020Article
- Omecamtiv Mecarbil Slows Myosin Kinetics in Skinned Rat Myocardium at Physiological Temperature.Biophysical journal · 2019Article
- Kinetic coupling of phosphate release, force generation and rate-limiting steps in the cross-bridge cycle.Journal of muscle research and cell motility · 2017Review
- Postnatal Development of Right Ventricular Myofibrillar Biomechanics in Relation to the Sarcomeric Protein Phenotype in Pediatric Patients with Conotruncal Heart Defects.Journal of the American Heart Association · 2016Observational
- Myofilament Calcium Sensitivity: Mechanistic Insight into TnI Ser-23/24 and Ser-150 Phosphorylation Integration.Frontiers in physiology · 2016Article
- Myofilament Calcium Sensitivity: Consequences of the Effective Concentration of Troponin I.Frontiers in physiology · 2016Article
- Effects of fatigue on the electromechanical delay components in gastrocnemius medialis muscle.European journal of applied physiology · 2014Article
- Kinetic mechanism of Ca²⁺-controlled changes of skeletal troponin I in psoas myofibrils.Biophysical journal · 2012Article
- The rates of Ca2+ dissociation and cross-bridge detachment from ventricular myofibrils as reported by a fluorescent cardiac troponin C.The Journal of biological chemistry · 2012Article
- Kinetics of regulated actin transitions measured by probes on tropomyosin.Biophysical journal · 2010Article
- Article
- The cardiac troponin C mutation Leu29Gln found in a patient with hypertrophic cardiomyopathy does not alter contractile parameters in skinned murine myocardium.Basic research in cardiology · 2009Article
- Förster resonance energy transfer structural kinetic studies of cardiac thin filament deactivation.The Journal of biological chemistry · 2009Article
- Insights into the kinetics of Ca2+-regulated contraction and relaxation from myofibril studies.Pflugers Archiv : European journal of physiology · 2009Article
- Dynamics of thin-filament activation in rabbit skeletal muscle fibers examined by time-resolved x-ray diffraction.Biophysical journal · 2009Article
- The cardiac Ca2+-sensitive regulatory switch, a system in dynamic equilibrium.Biophysical journal · 2008Article
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The kinetics of Ca(2+)-dependent conformational changes of human cardiac troponin (cTn) were studied on isolated cTn and within the sarcomeric environment of myofibrils. Human cTnC was selectively labeled on cysteine 84 with N-((2-(iodoacetoxy)ethyl)-N-methyl)amino-7-nitrobenz-2-oxa-1,3-diazole and reconstituted with cTnI and cTnT to the cTn complex, which was incorporated into guinea pig cardiac myofibrils. These exchanged myofibrils, or the isolated cTn, were rapidly mixed in a stopped-flow apparatus with different [Ca(2+)] or the Ca(2+)-buffer 1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid to determine the kinetics of the switch-on or switch-off, respectively, of cTn. Activation of myofibrils with high [Ca(2+)] (pCa 4.6) induced a biphasic fluorescence increase with rate constants of >2000 s(-1) and approximately 330 s(-1), respectively. At low [Ca(2+)] (pCa 6.6), the slower rate was reduced to approximately 25 s(-1), but was still approximately 50-fold higher than the rate constant of Ca(2+)-induced myofibrillar force development measured in a mechanical setup. Decreasing [Ca(2+)] from pCa 5.0-7.9 induced a fluorescence decay with a rate constant of 39 s(-1), which was approximately fivefold faster than force relaxation. Modeling the data indicates two sequentially coupled conformational changes of cTnC in myofibrils: 1), rapid Ca(2+)-binding (k(B) approximately 120 microM(-1) s(-1)) and dissociation (k(D) approximately 550 s(-1)); and 2), slower switch-on (k(on) = 390s(-1)) and switch-off (k(off) = 36s(-1)) kinetics. At high [Ca(2+)], approximately 90% of cTnC is switched on. Both switch-on and switch-off kinetics of incorporated cTn were around fourfold faster than those of isolated cTn. In conclusion, the switch kinetics of cTn are sensitively changed by its structural integration in the sarcomere and directly rate-limit neither cardiac myofibrillar contraction nor relaxation.
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