GO:0055117 regulation of cardiac muscle contraction: Calcium Signaling, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0055117 regulation of cardiac muscle contraction describes any process that modulates the frequency, rate or extent of cardiac muscle contraction.
• Intracellular Ca2+ is the central regulator of cardiac muscle contraction, linking excitation to contraction.
• Redox signaling modulates cardiac calcium handling and contractile function.
• Circadian regulation influences cardiac muscle function and protein degradation.
• MicroRNAs such as miR-1 and RNA-binding proteins like G3bp1 regulate cardiomyocyte hypertrophy.
• CRISPR-based models enable precise dissection of genes controlling cardiac contractility.
Description
Regulation of cardiac muscle contraction (GO:0055117) is a fundamental biological process that governs the frequency, rate, and extent of heart muscle contraction. This process is essential for maintaining cardiac output and responding to physiological demands. Dysregulation of this process underlies numerous cardiac pathologies, including heart failure and arrhythmias. Understanding the molecular mechanisms that control cardiac contractility is therefore critical for developing therapeutic strategies. The process involves intricate calcium signaling, redox modulation, and circadian control, with contributions from a wide array of genes and regulatory pathways. Recent advances in CRISPR gene editing have enabled researchers to create precise cellular and animal models to study these regulatory mechanisms. This article synthesizes current knowledge on GO:0055117, highlighting key genes, research methods, and the importance of this process in health and disease.
regulation of cardiac muscle contraction At A Glance
| GO ID | GO:0055117 |
|---|---|
| GO term | regulation of cardiac muscle contraction |
| Ontology | biological_process |
| Synonym | none |
| Major function | Modulates the frequency, rate, and extent of cardiac muscle contraction |
| Key regulators | Intracellular Ca2+, redox state, circadian clock, microRNAs |
| Related processes | Excitation-contraction coupling, calcium signaling, cardiac hypertrophy |
| Disease relevance | Heart failure, arrhythmias, cardiomyopathies |
What Is GO:0055117?
According to the Gene Ontology, GO:0055117 regulation of cardiac muscle contraction is defined as any process that modulates the frequency, rate or extent of cardiac muscle contraction. This encompasses molecular, cellular, and systemic mechanisms that influence the strength and timing of heart muscle contraction, including calcium handling, signaling cascades, and gene expression changes.
Why Is regulation of cardiac muscle contraction Important in Cell Biology?
Regulation of cardiac muscle contraction is vital for normal heart function, and its disruption leads to severe cardiovascular diseases such as heart failure and arrhythmias. Understanding this process at the molecular level is essential for identifying therapeutic targets and developing interventions. Moreover, the heart's regenerative capacity, as seen in zebrafish, highlights the importance of regulatory mechanisms in cardiac repair. Research into GO:0055117 also informs efforts in regenerative medicine and direct reprogramming of fibroblasts into cardiomyocytes.
• Maintains cardiac output and responds to physiological demands.
• Dysregulation causes heart failure, arrhythmias, and cardiomyopathies.
• Calcium signaling is central to excitation-contraction coupling.
• Redox regulation modulates calcium handling and contractility.
• Circadian rhythms influence cardiac function and protein degradation.
• MicroRNAs and RNA-binding proteins regulate cardiomyocyte hypertrophy.
• Zebrafish heart regeneration provides insights into cardiac repair.
• Direct reprogramming offers potential for regenerative therapies.
• CRISPR models enable precise genetic dissection of contractility.
• Fluorescence lifetime assays allow real-time monitoring of structural changes.
What Happens During regulation of cardiac muscle contraction?
Calcium Signaling and Excitation-Contraction Coupling
In simple terms: Calcium ions act as the switch that turns on heart muscle contraction.
Intracellular Ca2+ is the primary regulator of cardiac muscle contraction. During excitation-contraction coupling, depolarization of the cardiomyocyte membrane triggers Ca2+ influx through L-type calcium channels, which in turn activates ryanodine receptors on the sarcoplasmic reticulum, causing a massive release of Ca2+. This calcium binds to troponin C, shifting tropomyosin and allowing actin-myosin cross-bridge formation, leading to contraction. Relaxation occurs when Ca2+ is reuptaken into the sarcoplasmic reticulum by SERCA2a and extruded via the Na+/Ca2+ exchanger.
Redox Regulation of Calcium Signaling
In simple terms: Oxidation and reduction reactions can fine-tune calcium signals in heart cells.
Redox regulation modulates cardiac muscle calcium signaling. Reactive oxygen species (ROS) can modify cysteine residues on calcium-handling proteins, affecting their activity. For example, oxidation of ryanodine receptors can increase their open probability, enhancing Ca2+ release. This redox sensitivity allows the heart to adapt to oxidative stress but can also contribute to pathology when dysregulated.
Circadian Control of Cardiac Function
In simple terms: The body clock influences how well the heart pumps and how it maintains its proteins.
Circadian regulation of cardiac muscle function and protein degradation plays a role in modulating contractility. The molecular clock components regulate the expression of genes involved in calcium handling and contractile proteins, thereby influencing the frequency and strength of contraction over the day-night cycle. Disruption of circadian rhythms has been linked to cardiac dysfunction.
MicroRNA and RNA-Binding Protein Regulation
In simple terms: Small RNA molecules and RNA-binding proteins control heart cell growth and function.
The G3bp1-microRNA-1 axis regulates cardiomyocyte hypertrophy. MicroRNA-1 (miR-1) is a muscle-specific microRNA that targets genes involved in cardiac growth and contractility. G3bp1, an RNA-binding protein, modulates miR-1 processing and activity, thereby influencing hypertrophic responses. This axis represents a post-transcriptional layer of regulation of cardiac muscle contraction.
Structural Changes and Fluorescence Lifetime Assays
In simple terms: Advanced imaging can detect tiny structural changes in heart muscle proteins during contraction.
Fluorescence lifetime-based assays report structural changes in cardiac muscle mediated by effectors of contractile regulation. These assays can monitor conformational changes in myosin and other contractile proteins in real time, providing insights into how regulatory proteins and small molecules modulate contraction.
Key Genes Involved in GO:0055117 regulation of cardiac muscle contraction
Key genes and proteins involved in the regulation of cardiac muscle contraction include calcium-handling proteins, signaling molecules, and transcription factors.
| Gene | Major Role | Research Relevance |
|---|---|---|
| RYR2 | Ryanodine receptor 2, mediates Ca2+ release from sarcoplasmic reticulum | Mutations linked to arrhythmias; target for contractility studies |
| ATP2A2 (SERCA2a) | Sarcoplasmic reticulum Ca2+-ATPase, reuptakes Ca2+ during relaxation | Key regulator of relaxation; target for heart failure therapy |
| TNNT2 | Troponin T, part of thin filament regulatory complex | Mutations cause hypertrophic cardiomyopathy |
| MYH7 | Beta-myosin heavy chain, motor protein for contraction | Mutations associated with cardiomyopathies |
| CACNA1C | L-type calcium channel, mediates Ca2+ influx | Target for calcium channel blockers; involved in Timothy syndrome |
| NPPA | Atrial natriuretic peptide, marker of cardiac hypertrophy | Used as readout in hypertrophy studies |
| G3BP1 | RNA-binding protein, regulates miR-1 processing | Modulates cardiomyocyte hypertrophy |
| MIR1-1 | MicroRNA-1, regulates cardiac growth and contractility | Involved in hypertrophy and arrhythmogenesis |
| CLOCK | Core circadian clock transcription factor | Regulates cardiac gene expression and contractility |
| ARNTL (BMAL1) | Circadian clock transcription factor | Partners with CLOCK to regulate cardiac function |
| NOS1 | Neuronal nitric oxide synthase, produces NO | Modulates calcium handling and redox state |
| NOS3 | Endothelial nitric oxide synthase | Regulates cardiac contractility via NO signaling |
| SLC8A1 (NCX1) | Na+/Ca2+ exchanger, extrudes Ca2+ during relaxation | Important for calcium homeostasis |
| PLN | Phospholamban, inhibits SERCA2a | Regulated by phosphorylation to control relaxation |
| CAMK2D | Calcium/calmodulin-dependent protein kinase II | Phosphorylates calcium-handling proteins |
| PRKAA2 (AMPK) | AMP-activated protein kinase | Regulates energy metabolism and contractility |
How Is regulation of cardiac muscle contraction Regulated?
Regulation of cardiac muscle contraction is itself regulated by multiple signaling pathways. The circadian clock modulates the expression of contractile and calcium-handling genes. Redox signaling via reactive oxygen species can modify calcium channels and transporters. MicroRNAs, such as miR-1, and RNA-binding proteins like G3bp1 provide post-transcriptional control. Additionally, phosphorylation by kinases such as CAMK2D and PKA alters the activity of key calcium-handling proteins.
regulation of cardiac muscle contraction and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| RYR2 | CPVT, arrhythmias | Knock-in mouse with RYR2 mutation |
| ATP2A2 | Heart failure, impaired relaxation | Overexpression of SERCA2a in cardiomyocytes |
| G3BP1 | Cardiac hypertrophy | Knockout or overexpression in cardiomyocytes |
| CLOCK | Circadian disruption, cardiac dysfunction | Clock knockout mouse |
| TNNT2 | Hypertrophic cardiomyopathy | Point mutation knock-in mouse |
Heart Failure
Heart failure is characterized by impaired cardiac contractility and relaxation. Dysregulation of calcium handling, including reduced SERCA2a activity and increased NCX1 expression, contributes to contractile dysfunction. Redox stress further exacerbates calcium mishandling. Targeting these pathways is a major therapeutic strategy.
Arrhythmias
Arrhythmias often arise from abnormal calcium signaling. Mutations in RYR2 or CACNA1C can cause catecholaminergic polymorphic ventricular tachycardia (CPVT) or Timothy syndrome, respectively. Circadian disruption has also been linked to increased arrhythmia susceptibility.
Cardiac Hypertrophy
Pathological cardiac hypertrophy involves changes in gene expression and contractile protein function. The G3bp1-miR-1 axis regulates hypertrophic growth, and its dysregulation can lead to heart failure. Circadian clock genes also influence hypertrophic responses.
From regulation of cardiac muscle contraction-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Role of a specific gene in contractility | Knockout cardiomyocytes or mouse |
| Effect of a point mutation on calcium handling | Point mutation knock-in via CRISPR |
| Tagging a contractile protein for imaging | Knock-in of fluorescent tag |
| Overexpression of a signaling molecule | Overexpression in cardiomyocytes |
| High-throughput screening of regulators | CRISPR library screening |
| Circadian regulation of contractility | Clock knockout or reporter models |
How to Study the regulation of cardiac muscle contraction Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Calcium imaging | Intracellular Ca2+ transients | Assess excitation-contraction coupling |
| Fluorescence lifetime imaging | Structural changes in contractile proteins | Monitor myosin conformational changes |
| CRISPR screening | Gene function in contractility | Identify novel regulators |
| RNA-seq | Gene expression changes | Study hypertrophy and circadian regulation |
| Proteomics | Protein abundance and modifications | Analyze calcium-handling proteins |
| Patch clamp | Ion channel activity | Measure L-type calcium currents |
| Traction force microscopy | Contractile force | Evaluate cardiomyocyte contractility |
Calcium Imaging
Calcium imaging using fluorescent dyes or genetically encoded indicators allows real-time measurement of intracellular Ca2+ transients in cardiomyocytes. This method is essential for studying excitation-contraction coupling and the effects of genetic manipulations.
Fluorescence Lifetime Imaging (FLIM)
FLIM-based assays can report structural changes in cardiac muscle proteins, such as myosin, during contraction. This technique provides insights into the conformational dynamics of contractile proteins and the effects of regulatory effectors.
CRISPR Screening
CRISPR library screening enables unbiased identification of genes that regulate cardiac muscle contraction. Pooled screens with readouts such as calcium transients or contractility can uncover novel regulators.
Transcriptomics and Proteomics
RNA-seq and proteomics can reveal changes in gene and protein expression underlying cardiac hypertrophy and contractile dysfunction. These approaches are useful for studying circadian and microRNA-mediated regulation.
How CRISPR Can Be Used to Study GO:0055117 regulation of cardiac muscle contraction
Knockout
CRISPR knockout of candidate genes in cardiomyocytes or animal models allows assessment of their necessity for cardiac muscle contraction. For example, knocking out G3bp1 can reveal its role in hypertrophy.
Point Mutation
Introducing precise point mutations via CRISPR base editing or HDR can model human disease variants, such as those in RYR2 or TNNT2, to study their effects on contractility.
Knock-in
Knock-in of reporter genes or tags, such as fluorescent proteins, enables real-time imaging of contractile proteins and their dynamics.
Overexpression
CRISPR activation (CRISPRa) or transgenic overexpression can increase the expression of genes like SERCA2a to study their impact on cardiac function.
How EDITGENE Supports regulation of cardiac muscle contraction Research
Researchers studying regulation of cardiac muscle contraction-related genes often need to determine whether a candidate gene is causally involved in contractile regulation. This requires precise genetic models to manipulate gene expression and function.
Contact EDITGENE today to design your custom CRISPR model for regulation of cardiac muscle contraction research.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SCN10A Overexpression HEK293T Stable Cell Line | EDC01586 | Human | 6336 | Details Get a Quote |
| SMAD7 Knockout HEK293 Cell Line | EDJ-KQ403 | Human | 4092 | Details Get a Quote |
| PRKACA Knockout HEK293 Cell Line | EDJ-KQ738 | Human | 5566 | Details Get a Quote |
| NOS1 Knockout HEK293 Cell Line | EDJ-KQ844 | Human | 4842 | Details Get a Quote |
| CALM3 Knockout HEK293 Cell Line | EDJ-KQ1223 | Human | 808 | Details Get a Quote |
| RYR2 Knockout HEK293 Cell Line | EDJ-KQ1426 | Human | 6262 | Details Get a Quote |
| P2RX4 Knockout HEK293 Cell Line | EDJ-KQ1573 | Human | 5025 | Details Get a Quote |
| ADRA1A Knockout HEK293 Cell Line | EDJ-KQ1583 | Human | 148 | Details Get a Quote |
| ADRA1B Knockout HEK293 Cell Line | EDJ-KQ1584 | Human | 147 | Details Get a Quote |
| ADORA1 Knockout HEK293 Cell Line | EDJ-KQ1750 | Human | 134 | Details Get a Quote |
| HCN4 Knockout HEK293 Cell Line | EDJ-KQ1798 | Human | 10021 | Details Get a Quote |
| GJA5 Knockout HEK293 Cell Line | EDJ-KQ2494 | Human | 2702 | Details Get a Quote |
| ANK2 Knockout HEK293 Cell Line | EDJ-KQ2889 | Human | 287 | Details Get a Quote |
| CAV3 Knockout HEK293 Cell Line | EDJ-KQ4196 | Human | 859 | Details Get a Quote |
| SCN5A Knockout HEK293 Cell Line | EDJ-KQ4969 | Human | 6331 | Details Get a Quote |
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Frequently Asked Questions About regulation of cardiac muscle contraction
What is GO:0055117 regulation of cardiac muscle contraction?
GO:0055117 is a Gene Ontology biological process term defined as any process that modulates the frequency, rate or extent of cardiac muscle contraction.
What genes are involved in regulation of cardiac muscle contraction?
Key genes include RYR2, ATP2A2, TNNT2, MYH7, CACNA1C, G3BP1, MIR1-1, CLOCK, and NOS1, among others.
How does calcium regulate cardiac muscle contraction?
Intracellular Ca2+ binds to troponin C, triggering conformational changes that allow actin-myosin cross-bridge formation and contraction.
What is the role of redox signaling in cardiac contraction?
Redox signaling modulates calcium-handling proteins through oxidation, affecting their activity and thus contractility.
How does the circadian clock affect heart contraction?
The circadian clock regulates the expression of genes involved in calcium handling and contractile proteins, influencing cardiac function over the day-night cycle.
What is the G3bp1-miR-1 axis?
G3bp1 regulates the processing of microRNA-1, which controls cardiomyocyte hypertrophy and contractility.
What research methods are used to study cardiac muscle contraction regulation?
Methods include calcium imaging, fluorescence lifetime imaging, CRISPR screening, RNA-seq, proteomics, and patch clamp.
How can CRISPR be used to study cardiac contractility genes?
CRISPR enables knockout, point mutation, knock-in, and overexpression of candidate genes in cardiomyocytes or animal models to assess their function.
What diseases are linked to dysregulation of cardiac muscle contraction?
Heart failure, arrhythmias, and cardiac hypertrophy are major diseases linked to dysregulation of cardiac contractility.
What models are available for studying cardiac muscle contraction regulation?
Models include knockout mice, point mutation knock-in mice, fluorescently tagged proteins, and overexpression systems.
Conclusion
Regulation of cardiac muscle contraction (GO:0055117) is a complex biological process essential for heart function. It involves calcium signaling, redox modulation, circadian control, and post-transcriptional regulation. Dysregulation leads to major cardiovascular diseases. Advances in CRISPR gene editing and imaging technologies continue to unravel the molecular players, offering hope for novel therapeutic interventions.
References
- 1. Yoo SH. 2023. Circadian regulation of cardiac muscle function and protein degradation.. Chronobiol Int 40(1):4-12 PMID: 34521283
- 2. Kurihara S. 1994. Regulation of cardiac muscle contraction by intracellular Ca2+.. Jpn J Physiol 44(6):591-611 PMID: 7760518
- 3. Poss KD et al.. 2002. Heart regeneration in zebrafish.. Science 298(5601):2188-90 PMID: 12481136
- 4. Korzick DH. 2003. Regulation of cardiac excitation-contraction coupling: a cellular update.. Adv Physiol Educ 27(1-4):192-200 PMID: 14627617
- 5. Morad M et al.. 2000. Redox regulation of cardiac muscle calcium signaling.. Antioxid Redox Signal 2(1):65-71 PMID: 11232602
- 6. Ieda M et al.. 2010. Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors.. Cell 142(3):375-86 PMID: 20691899
- 7. Dvornikov AV et al.. 2023. Fluorescence lifetime-based assay reports structural changes in cardiac muscle mediated by effectors of contractile regulation.. J Gen Physiol 155(3) PMID: 36633587
- 8. Alikunju S et al.. 2022. G3bp1 - microRNA-1 axis regulates cardiomyocyte hypertrophy.. Cell Signal 91:110245 PMID: 35017014
