ArticleBiophysical journal2008
Calmodulin mediates differential sensitivity of CaMKII and calcineurin to local Ca2+ in cardiac myocytes.
Article in Biophysical journal, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
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Who cites it
98 citing papers in PubMed, 152 citations in OpenAlex.
- The slow delayed rectifier KScientific reports · 2025Article
- Modeling autoregulation of cardiac excitation-Ca-contraction and arrhythmogenic activities in response to mechanical load changes.iScience · 2025Article
- Long QT syndrome type 3 gain-of-function of NaCommunications biology · 2025Article
- A novel computational model of swine ventricular myocyte reveals new insights into disease mechanisms and therapeutic approaches in Timothy Syndrome.Scientific reports · 2024Article
- Computational Modeling of Cardiac Electrophysiology.Methods in molecular biology (Clifton, N.J.) · 2024Article
- CaMK II in Cardiovascular Diseases, Especially CaMK II-δ: Friends or Enemies.Drug design, development and therapy · 2024Review
- Integrative human atrial modelling unravels interactive protein kinase A and Ca2+/calmodulin-dependent protein kinase II signalling as key determinants of atrial arrhythmogenesis.Cardiovascular research · 2023Article
- Physiology of intracellular calcium buffering.Physiological reviews · 2023Review
- "Dirty Dancing" of Calcium and Autophagy in Alzheimer's Disease.Life (Basel, Switzerland) · 2023Review
- Gating kinetics and pharmacological properties of small-conductance CaBiophysical journal · 2023Article
- A Gating Mutation in Ryanodine Receptor Type 2 Rescues Phenotypes of Alzheimer's Disease Mouse Models by Upregulating Neuronal Autophagy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Nanoscale organization of ryanodine receptor distribution and phosphorylation pattern determines the dynamics of calcium sparks.PLoS computational biology · 2022Article
- AKAP18δ Anchors and Regulates CaMKII Activity at Phospholamban-SERCA2 and RYR.Circulation research · 2022Article
- CaMKIIδ post-translational modifications increase affinity for calmodulin inside cardiac ventricular myocytes.Journal of molecular and cellular cardiology · 2021Article
- Quantitative cross-species translators of cardiac myocyte electrophysiology: Model training, experimental validation, and applications.Science advances · 2021Article
- CaMKII and PKA-dependent phosphorylation co-regulate nuclear localization of HDAC4 in adult cardiomyocytes.Basic research in cardiology · 2021Article
- FGF19/SOCE/NFATc2 signaling circuit facilitates the self-renewal of liver cancer stem cells.Theranostics · 2021Article
- CaBiophysical journal · 2020Article
- The nuclear envelope: LINCing tissue mechanics to genome regulation in cardiac and skeletal muscle.Biology letters · 2020Article
- Non-invasive optical control of endogenous CaNature communications · 2020Article
38 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Calmodulin (CaM) mediates Ca-dependent regulation of numerous pathways in the heart, including CaM-dependent kinase (CaMKII) and calcineurin (CaN), yet the local Ca(2+) signals responsible for their selective activation are unclear. To assess when and where CaM, CaMKII, and CaN may be activated in the cardiac myocyte, we integrated new mechanistic computational models of CaM, CaMKII, and CaN with the Shannon-Bers model of excitation-contraction coupling in the rabbit ventricular myocyte. These models are validated with independent in vitro data. In the intact myocyte, model simulations predict that CaM is highly activated in the dyadic cleft during each beat, but not appreciably in the cytosol. CaMKII-delta(C) was almost insensitive to cytosolic Ca due to relatively low CaM affinity. Dyadic cleft CaMKII exhibits dynamic frequency-dependent responses to Ca, yet autophosphorylates only when local phosphatases are suppressed. In contrast, dyadic cleft CaN in beating myocytes is predicted to be constitutively active, whereas the extremely high affinity of CaN for CaM allows gradual integration of small cytosolic CaM signals. Reversing CaM affinities for CaMKII and CaN also reverses their characteristic local responses. Deactivation of both CaMKII and CaN seems dominated by Ca dissociation from the complex (versus Ca-CaM dissociation from the target). In summary, the different affinities of CaM for CaMKII and CaN determine their sensitivity to local Ca signals in cardiac myocytes.
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