Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (727 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
A process fundamental to muscle physiology whereby an electrical stimulus or action potential triggers a myocyte to depolarize and contract. This mechanical muscle contraction response is regulated by entry of calcium ions into the cell.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Contraction Coupling, Excitation; Contraction Couplings, Excitation; Coupling, Excitation Contraction; Couplings, Excitation Contraction; Excitation Contraction Couplings.
Where it fits in the MeSH classification
- Broader topics
- Calcium Signaling; Signal Transduction; Muscle Contraction
Research landscape
PubMed indexes 899 records tagged with the MeSH heading “Excitation Contraction Coupling” (counts retrieved 2026-10-29). 184 of them (20.5%) were published from 2020 onward, and the busiest period so far is 2010-2019 with 697 records.
Reviews account for 214 records (23.8%) and meta-analyses for 0. Randomized controlled trials number 4 (0.4%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 0 |
| 2000-2009 | 20 |
| 2010-2019 | 697 |
| 2020 onward | 184 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 214 | 23.8% |
| Meta-analyses | 0 | 0.0% |
| Randomized controlled trials | 4 | 0.4% |
Method: PubMed query "Excitation Contraction Coupling"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in molecular biology
Molecular biology establishes mechanisms through controlled experiments, often in simplified systems such as purified proteins, cultured cells or model organisms. Such work can show what is possible in a defined system, but whether a pathway matters in a whole organism or in human disease needs further evidence. Check the experimental system, whether findings were reproduced by independent groups, and whether the authors tested the mechanism directly or inferred it from correlation.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Calcium and Excitation-Contraction Coupling in the Heart | 2017 | Review article Design not recorded in structured metadata | 714 | cc by PMID 28684623 · DOI · PMC5497788 |
| Ca2+-dependent regulations and signaling in skeletal muscle: from electro-mechanical coupling to adaptation | 2015 | Review article Design not recorded in structured metadata | 143 | cc by PMID 25569087 · DOI · PMC4307291 |
| Changes in the organization of excitation-contraction coupling structures in failing human heart | 2011 | Research article Design not recorded in structured metadata | 126 | cc by PMID 21408028 · DOI · PMC3052389 |
| 14-3-3 proteins: Regulators of cardiac excitation-contraction coupling and stress responses | 2026 | Review article Design not recorded in structured metadata | 2 | cc by PMID 40349303 · DOI · PMC12459269 |
Calcium and Excitation-Contraction Coupling in the Heart [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Cardiac contractility is regulated by changes in intracellular Ca concentration ([Ca2+]i).
- Closing excerpt
- The remainder of the review considers specific aspects of Ca signaling, including the role of Ca buffers, mitochondria, Ca leak, and regulation of diastolic [Ca2+]i.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (164 words)
Cardiac contractility is regulated by changes in intracellular Ca concentration ([Ca2+]i). Normal function requires that [Ca2+]i be sufficiently high in systole and low in diastole. Much of the Ca needed for contraction comes from the sarcoplasmic reticulum and is released by the process of calcium-induced calcium release. The factors that regulate and fine-tune the initiation and termination of release are reviewed. The precise control of intracellular Ca cycling depends on the relationships between the various channels and pumps that are involved. We consider 2 aspects: (1) structural coupling: the transporters are organized within the dyad, linking the transverse tubule and sarcoplasmic reticulum and ensuring close proximity of Ca entry to sites of release. (2) Functional coupling: where the fluxes across all membranes must be balanced such that, in the steady state, Ca influx equals Ca efflux on every beat. The remainder of the review considers specific aspects of Ca signaling, including the role of Ca buffers, mitochondria, Ca leak, and regulation of diastolic [Ca2+]i.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 28684623 · DOI · PMC5497788
Ca2+-dependent regulations and signaling in skeletal muscle: from electro-mechanical coupling to adaptation [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Calcium (Ca2+) plays a pivotal role in almost all cellular processes and ensures the functionality of an organism.
- Closing excerpt
- In this review, we address the major functions of Ca(2+) ions in adult muscle but also highlight recent findings of critical Ca(2+)-dependent mechanisms essential for skeletal muscle-regulation and maintenance.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (137 words)
Calcium (Ca2+) plays a pivotal role in almost all cellular processes and ensures the functionality of an organism. In skeletal muscle fibers, Ca(2+) is critically involved in the innervation of skeletal muscle fibers that results in the exertion of an action potential along the muscle fiber membrane, the prerequisite for skeletal muscle contraction. Furthermore and among others, Ca(2+) regulates also intracellular processes, such as myosin-actin cross bridging, protein synthesis, protein degradation and fiber type shifting by the control of Ca(2+)-sensitive proteases and transcription factors, as well as mitochondrial adaptations, plasticity and respiration. These data highlight the overwhelming significance of Ca(2+) ions for the integrity of skeletal muscle tissue. In this review, we address the major functions of Ca(2+) ions in adult muscle but also highlight recent findings of critical Ca(2+)-dependent mechanisms essential for skeletal muscle-regulation and maintenance.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 25569087 · DOI · PMC4307291
Changes in the organization of excitation-contraction coupling structures in failing human heart [3]
Abstract reading summary — source excerpts
- Opening excerpt
- BackgroundThe cardiac myocyte t-tubular system ensures rapid, uniform cell activation and several experimental lines of evidence suggest changes in the t-tubular system and associated excitation-contraction coupling proteins may occur in heart failure.
- Closing excerpt
- The general organization of the t-system and changes observed in failure samples have subtle differences to some animal models although the general direction of changes are generally similar.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (251 words)
BackgroundThe cardiac myocyte t-tubular system ensures rapid, uniform cell activation and several experimental lines of evidence suggest changes in the t-tubular system and associated excitation-contraction coupling proteins may occur in heart failure.Methods and resultsThe organization of t-tubules, L-type calcium channels (DHPRs), ryanodine receptors (RyRs) and contractile machinery were examined in fixed ventricular tissue samples from both normal and failing hearts (idiopathic (non-ischemic) dilated cardiomyopathy) using high resolution fluorescent imaging. Wheat germ agglutinin (WGA), Na-Ca exchanger, DHPR and caveolin-3 labels revealed a shift from a predominantly transverse orientation to oblique and axial directions in failing myocytes. In failure, dilation of peripheral t-tubules occurred and a change in the extent of protein glycosylation was evident. There was no change in the fractional area occupied by myofilaments (labeled with phalloidin) but there was a small reduction in the number of RyR clusters per unit area. The general relationship between DHPRs and RyR was not changed and RyR labeling overlapped with 51±3% of DHPR labeling in normal hearts. In longitudinal (but not transverse) sections there was an ∼30% reduction in the degree of colocalization between DHPRs and RyRs as measured by Pearson's correlation coefficient in failing hearts.ConclusionsThe results show that extensive remodelling of the t-tubular network and associated excitation-contraction coupling proteins occurs in failing human heart. These changes may contribute to abnormal calcium handling in heart failure. The general organization of the t-system and changes observed in failure samples have subtle differences to some animal models although the general direction of changes are generally similar.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 21408028 · DOI · PMC3052389
14-3-3 proteins: Regulators of cardiac excitation-contraction coupling and stress responses [4]
Abstract reading summary — source excerpts
- Opening excerpt
- 14-3-3 proteins are highly conserved proteins that regulate numerous cellular processes mostly through phosphorylation-dependent protein-protein interactions.
- Closing excerpt
- Understanding the complex regulation of cardiac 14-3-3 and its numerous targets presents both opportunities and challenges for therapeutic development.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (175 words)
14-3-3 proteins are highly conserved proteins that regulate numerous cellular processes mostly through phosphorylation-dependent protein-protein interactions. In the heart 14-3-3 proteins play critical roles in cardiac conduction pathways, excitation-contraction (EC) coupling, development and stress responses. This review summarizes the current understanding of cardiac 14-3-3 regulation and function, with particular emphasis on its role in ion channel regulation and β-adrenergic signalling. We discuss how 14-3-3 proteins act through three main mechanisms - masking, clamping, and scaffolding - to regulate target proteins, including Cx43, CaV1.2, NaV1.5, and various potassium channels. The seven mammalian 14-3-3 isoforms display distinct but overlapping functions, with tissue-specific expression patterns and isoform-specific regulation through phosphorylation and dimerization. Recent work has revealed 14-3-3's importance in cardiac development and stress responses, where it generally serves a cardioprotective role. However in some pathological contexts such as ischaemia-reperfusion injury, 14-3-3 can be detrimental. We highlight emerging themes in cardiac 14-3-3 biology, including its role in prolonging β-adrenergic signalling. Understanding the complex regulation of cardiac 14-3-3 and its numerous targets presents both opportunities and challenges for therapeutic development.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 40349303 · DOI · PMC12459269
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Mechanisms of altered Ca²⁺ handling in heart failure [5]
- Research article Redox signaling in cardiac myocytes [6]
- Research article Congenital myopathies: disorders of excitation-contraction coupling and muscle contraction [7]
- Research article Fibroblast-myocyte electrotonic coupling: does it occur in native cardiac tissue? [8]
- Research article Mechanisms of enhanced force production in lengthening (eccentric) muscle contractions [9]
- Research article Sex differences in mechanisms of cardiac excitation-contraction coupling [10]
References
- Eisner DA, Caldwell JL, Kistamás K, Trafford AW. Calcium and Excitation-Contraction Coupling in the Heart. . 2017. PMID 28684623 · DOI · PMC5497788
- Gehlert S, Bloch W, Suhr F. Ca2+-dependent regulations and signaling in skeletal muscle: from electro-mechanical coupling to adaptation. . 2015. PMID 25569087 · DOI · PMC4307291
- Crossman DJ, Ruygrok PN, Soeller C, Cannell MB. Changes in the organization of excitation-contraction coupling structures in failing human heart. . 2011. PMID 21408028 · DOI · PMC3052389
- Spooner HC, Dixon RE. 14-3-3 proteins: Regulators of cardiac excitation-contraction coupling and stress responses. . 2026. PMID 40349303 · DOI · PMC12459269
- Luo M, Anderson ME. Mechanisms of altered Ca²⁺ handling in heart failure. Circ Res. 2013. PMID 23989713 · DOI · PMC4080816
- Santos CX, Anilkumar N, Zhang M, Brewer AC, Shah AM. Redox signaling in cardiac myocytes. Free Radic Biol Med. 2011. PMID 21236334 · DOI · PMC3049876
- Jungbluth H, Treves S, Zorzato F, Sarkozy A, Ochala J, Sewry C, et al.. Congenital myopathies: disorders of excitation-contraction coupling and muscle contraction. Nat Rev Neurol. 2018. PMID 29391587 · DOI
- Kohl P, Gourdie RG. Fibroblast-myocyte electrotonic coupling: does it occur in native cardiac tissue?. J Mol Cell Cardiol. 2014. PMID 24412581 · DOI · PMC4001130
- Herzog W. Mechanisms of enhanced force production in lengthening (eccentric) muscle contractions. J Appl Physiol (1985). 2014. PMID 23429875 · DOI
- Parks RJ, Howlett SE. Sex differences in mechanisms of cardiac excitation-contraction coupling. Pflugers Arch. 2013. PMID 23417603 · DOI · PMC3651827
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.