ArticleCell calcium2007
Free and bound intracellular calmodulin measurements in cardiac myocytes.
Article in Cell calcium, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 118 citations in OpenAlex.
- Catecholaminergic polymorphic ventricular tachycardia-linked ryanodine receptor variants exhibit domain-specific calcium leak and calmodulin affinity properties.The Journal of physiology · 2026Article
- Biomolecular condensation of cMLCK enables myosin motor phosphorylation in the heart.bioRxiv : the preprint server for biology · 2026Article
- Dynamic-Structure Redesign of Calmodulin Reveals Mechanistic Constraints on Ryr2 Regulation.bioRxiv : the preprint server for biology · 2026Article
- Calcium interaction with Nav1.5 via FGF12A and CaM binding.bioRxiv : the preprint server for biology · 2026Article
- History of Gap Junction Architecture and Potential Role of Calmodulin in Channel Arrays.International journal of molecular sciences · 2025Review
- Calmodulin D133H Disrupts CaCells · 2025Article
- Calmodulin enhancement of mitochondrial calcium uniporter function in isolated mitochondria.Cell calcium · 2025Article
- Calmodulin binding is required for calcium mediated TRPA1 desensitization.Nature communications · 2025Article
- Enrichment of mutant calmodulin protein in a murine model of a human calmodulinopathy.JCI insight · 2025Article
- The three calmodulin genes: territories defined?Cardiovascular research · 2025Article
- Casein Kinase 2 Regulates the Intrinsic Activity of L-Type Calcium Currents in Cardiomyocytes.International journal of molecular sciences · 2025Article
- Exploring biochemical considerations for diffusive alpha radiation therapy (DaRT) models.Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB) · 2025Review
- Kinetics and mapping of Ca-driven calmodulin conformations on skeletal and cardiac muscle ryanodine receptors.Nature communications · 2024Article
- Nernst-Planck-Gaussian finite element modelling of CaFrontiers in physiology · 2024Article
- Arrhythmia-associated calmodulin variants interact with KCNQ1 to confer aberrant membrane trafficking and function.PNAS nexus · 2023Article
- Human disease-associated calmodulin mutations alter calcineurin function through multiple mechanisms.Cell calcium · 2023Article
- NaV1.6 dysregulation within myocardial T-tubules by D96V calmodulin enhances proarrhythmic sodium and calcium mishandling.The Journal of clinical investigation · 2023Article
- Regulation of Cardiac Cav1.2 Channels by Calmodulin.International journal of molecular sciences · 2023Review
- Calmodulin mutations affecting Gly114 impair binding to the NaFrontiers in pharmacology · 2023Article
- Retinal Cyclic Nucleotide-Gated Channel Regulation by Calmodulin.International journal of molecular sciences · 2022Review
7 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Calmodulin (CaM) is a ubiquitous Ca2+ binding protein and Ca2+-CaM activates many cellular targets and functions. While much of CaM is thought to be protein bound, quantitative data in cardiac myocytes is lacking regarding CaM location, [CaM]free and CaM redistribution during changes in [Ca2+]i. Here, we demonstrated that in adult rabbit cardiac myocytes, CaM is highly concentrated at Z-lines (confirmed by Di-8-ANEPPS staining of transverse tubules) using three different approaches: immunocytochemistry (endogenous CaM), Alexa Fluor 488 conjugate CaM (F-CaM) in both permeabilized cells (exogenous CaM) and in patch clamped intact cells (via pipette dialysis). Using 100 nM [CaM]free we washed F-CaM into permeabilized myocytes and saw a two-phase (fast and slow) CaM binding curve with a plateau after 40 min of F-CaM wash-in. We also measured myocyte [CaM]free using two modified null-point titration methods, finding [CaM]free to be 50-75 nM (which is only 1% of total [CaM]). Higher [Ca2+]i increased CaM binding especially in the nucleus and at Z-lines and significantly slowed F-CaM dissociation rate when F-CaM was washed out of permeabilized myocytes. Additionally, in both permeabilized and intact myocytes, CaM moved into the nucleus when [Ca2+]i was elevated, and this was reversible. We conclude that [CaM]free is very low in myocytes even at resting [Ca2+]i, indicating intense competition of CaM targets for free CaM. Bound CaM is relatively concentrated at Z-lines at rest but translocates significantly to the nucleus upon elevation of [Ca2+]i, which may influence activation of different targets and cellular functions.
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