ArticleJournal of molecular and cellular cardiology2014
Combined troponin I Ser-150 and Ser-23/24 phosphorylation sustains thin filament Ca(2+) sensitivity and accelerates deactivation in an acidic environment.
Article in Journal of molecular and cellular cardiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 44 citations in OpenAlex.
- Myocardium From Patients With ATTR Amyloidosis Produces Less Force Secondary to Increased Fibrosis.JACC. Basic to translational science · 2025Article
- Dual role of Tropomyosin-R160 in thin filament regulation: Insights into phosphorylation-dependent cardiac relaxation and cardiomyopathy mechanisms.Archives of biochemistry and biophysics · 2025Article
- Hyperactive mTORC1/4EBP1 signaling dysregulates proteostasis and accelerates cardiac aging.GeroScience · 2025Article
- Abnormal phosphorylation / dephosphorylation and CaHeart failure reviews · 2024Review
- Mouse Models of Cardiomyopathies Caused by Mutations in Troponin C.International journal of molecular sciences · 2023Review
- The lack of Troponin I Ser-23/24 phosphorylation is detrimental to in vivo cardiac function and exacerbates cardiac disease.Journal of molecular and cellular cardiology · 2023Article
- Molecular regulation of stretch activation.American journal of physiology. Cell physiology · 2022Article
- A Simple and Effective Method to Consistently Isolate Mouse Cardiomyocytes.Journal of visualized experiments : JoVE · 2022Article
- Antiquated ejection fraction: Basic research applications for speckle tracking echocardiography.Frontiers in physiology · 2022Review
- NADCirculation. Heart failure · 2021Article
- Heart Failure in Humans Reduces Contractile Force in Myocardium From Both Ventricles.JACC. Basic to translational science · 2020Article
- Late-life restoration of mitochondrial function reverses cardiac dysfunction in old mice.eLife · 2020Article
- Site-specific acetyl-mimetic modification of cardiac troponin I modulates myofilament relaxation and calcium sensitivity.Journal of molecular and cellular cardiology · 2020Article
- Rats genetically selected for low and high aerobic capacity exhibit altered soleus muscle myofilament functions.American journal of physiology. Cell physiology · 2020Article
- Troponin I modulation of cardiac performance: Plasticity in the survival switch.Archives of biochemistry and biophysics · 2019Review
- Assessment of PKA and PKC inhibitors on force and kinetics of non-failing and failing human myocardium.Life sciences · 2018Article
- Facilitation of ischaemia-induced ventricular fibrillation by catecholamines is mediated by βBritish journal of pharmacology · 2018Article
- Functional communication between PKC-targeted cardiac troponin I phosphorylation sites.Archives of biochemistry and biophysics · 2017Article
- Long-Term Biased β-Arrestin Signaling Improves Cardiac Structure and Function in Dilated Cardiomyopathy.Circulation · 2017Article
- Cardiac troponin structure-function and the influence of hypertrophic cardiomyopathy associated mutations on modulation of contractility.Archives of biochemistry and biophysics · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The binding of Ca(2+) to troponin C (TnC) in the troponin complex is a critical step regulating the thin filament, the actin-myosin interaction and cardiac contraction. Phosphorylation of the troponin complex is a key regulatory mechanism to match cardiac contraction to demand. Here we demonstrate that phosphorylation of the troponin I (TnI) subunit is simultaneously increased at Ser-150 and Ser-23/24 during in vivo myocardial ischemia. Myocardial ischemia decreases intracellular pH resulting in depressed binding of Ca(2+) to TnC and impaired contraction. To determine the pathological relevance of these simultaneous TnI phosphorylations we measured individual TnI Ser-150 (S150D), Ser-23/24 (S23/24D) and combined (S23/24/150D) pseudo-phosphorylation effects on thin filament regulation at acidic pH similar to that in myocardial ischemia. Results demonstrate that while acidic pH decreased thin filament Ca(2+) binding to TnC regardless of TnI composition, TnI S150D attenuated this decrease rendering it similar to non-phosphorylated TnI at normal pH. The dissociation of Ca(2+) from TnC was unaltered by pH such that TnI S150D remained slow, S23/24D remained accelerated and the combined S23/24/150D remained accelerated. This effect of the combined TnI Ser-150 and Ser-23/24 pseudo-phosphorylations to maintain Ca(2+) binding while accelerating Ca(2+) dissociation represents the first post-translational modification of troponin by phosphorylation to both accelerate thin filament deactivation and maintain Ca(2+) sensitive activation. These data suggest that TnI Ser-150 phosphorylation induced attenuation of the pH-dependent decrease in Ca(2+) sensitivity and its combination with Ser-23/24 phosphorylation to maintain accelerated thin filament deactivation may impart an adaptive role to preserve contraction during acidic ischemia pH without slowing relaxation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.