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Updated: Aug 30, 2026

Contractility Measurements on Isolated Papillary Muscles for the Investigation of Cardiac Inotropy in Mice
Published on: September 17, 2015
Effect of MyBP-C binding to actin on contractility in heart muscle
Irina Kulikovskaya1, George McClellan, Jeanne Flavigny
1Department of Physiology, School of Medicine, University of Pennsylvania Philadelphia, PA 19104, USA.
Insights
Cardiac myosin binding protein C (MyBP-C) regulates heart muscle contraction. Its binding shifts between actin and myosin, influencing cardiac contractility and potentially diastolic filling.
Area of Science:
- Cardiology
- Muscle Physiology
- Molecular Biology
Background:
- Cardiac myosin binding protein C (MyBP-C) is a key regulator of cardiac muscle contraction.
- The cardiac isoform of MyBP-C differs structurally from skeletal isoforms, featuring additional modules and phosphorylation sites.
- Phosphorylation of MyBP-C influences Ca-activated force and filament interactions.
Purpose of the Study:
- To investigate the binding interactions of cardiac MyBP-C fragments with actin and myosin.
- To elucidate the role of MyBP-C's NH2 terminus in regulating cardiac contractility.
- To explore the potential impact of MyBP-C binding dynamics on diastolic heart function.
Main Methods:
- Utilized immunoprecipitation and cosedimentation assays to study MyBP-C fragment interactions.
- Employed skinned fiber preparations to assess binding under physiological conditions.
- Investigated the effects of disrupting MyBP-C interactions on cardiac contractility.
Main Results:
- Cardiac MyBP-C fragments containing the C0 module bind to actin.
- The C1C2 fragment binds to myosin when unphosphorylated and actin when phosphorylated.
- Disrupting endogenous C0 interactions mimics MyBP-C extraction, decreasing Fmax and increasing Ca sensitivity.
Conclusions:
- Cardiac contractility is regulated by the dynamic binding of MyBP-C's NH2 terminus between actin and myosin.
- This binding shift mechanism may play a role in regulating diastolic filling of the heart.
- Understanding these interactions provides insights into cardiac function and potential therapeutic targets.
Abstract:
In contrast to skeletal muscle isoforms of myosin binding protein C (MyBP-C), the cardiac isoform has 11 rather than 10 fibronectin or Ig modules (modules are identified as C0 to C10, NH2 to COOH terminus), 3 phosphorylation sites between modules C1 and C2, and 28 additional amino acids rich in proline in C5. Phosphorylation between C1 and C2 increases maximum Ca-activated force (Fmax), alters thick filament structure, and increases the probability of myosin heads on the thick filament binding to actin on the thin filament. Unphosphorylated C1C2 fragment binds to myosin, but phosphorylation inhibits the binding. MyBP-C also binds to actin. Using two types of immunoprecipitation and cosedimentation, we show that fragments of MyBP-C containing C0 bind to actin. In low concentrations C0-containing fragments bind to skinned fibers when the NH2 terminus of endogenous MyBP-C is bound to myosin, but not when MyBP-C is bound to actin. C1C2 fragments bind to skinned fibers when endogenous MyBP-C is bound to actin but not to myosin. Disruption of interactions of endogenous C0 with a high concentration of added C0C2 fragments produces the same effect on contractility as extraction of MyBP-C, namely decrease in Fmax and increase in Ca sensitivity. These results suggest that cardiac contractility can be regulated by shifting the binding of the NH2 terminus of MyBP-C between actin and myosin. This mechanism may have an effect on diastolic filling of the heart.
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