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.

Related Concept Videos

The Role of Actin and Myosin in Non-muscle Cells01:10

The Role of Actin and Myosin in Non-muscle Cells

Actin and myosin or actomyosin filaments also play a significant role in cells other than those involved in muscle contraction (which occurs within the sarcomere of muscle cells). The mechanism of non-muscle cell contractile bundles was first observed in Dictyostelium and Acanthamoeba. In non-muscle cells, two bundles are commonly found: stress fibers and actomyosin adherence belts. These contractile bundles are smaller and less organized than the ones found in muscle cells. They  are held...
Actin and Myosin in Muscle Contraction01:16

Actin and Myosin in Muscle Contraction

Actin and myosin are contractile proteins that form the sarcomere found in skeletal muscle tissues for regulating muscle contraction. Actin, a globular contractile protein, interacts with myosin for muscle contraction. The skeletal tissue appears striped or striated under a microscope due to the repeated arrangement of contractile proteins actin and myosin along the length of myofibrils. Dark A bands and light I bands repeat along myofibrils, and the alignment of myofibrils in the cell causes...
Smooth Muscle Contraction01:25

Smooth Muscle Contraction

Smooth muscle contraction is a complex process vital for various bodily functions, from maintaining blood vessel tension to facilitating the movement of food through the digestive tract. Unlike striated muscles, smooth muscle contraction begins more slowly and lasts longer.
The onset of contraction is triggered by an increase in calcium ions within the sarcoplasm, similar to the process in striated muscle. However, smooth muscles have a relatively smaller reservoir of the sarcoplasmic...
Cross-bridge Cycle01:26

Cross-bridge Cycle

As muscle contracts, the overlap between the thin and thick filaments increases, decreasing the length of the sarcomere—the contractile unit of the muscle—using energy in the form of ATP. At the molecular level, this is a cyclic, multistep process that involves binding and hydrolysis of ATP, and movement of actin by myosin.
G-Protein Gated Ion Channels01:21

G-Protein Gated Ion Channels

GPCRs are primarily responsible for our sense of smell, taste, and vision.  The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory organs,...
Specialized Characteristics of Cardiac Muscles01:27

Specialized Characteristics of Cardiac Muscles

The primary role of cardiac muscles is to propel blood throughout the cardiovascular system. The cardiac muscle cells, or cardiomyocytes, exhibit specialized characteristics that allow them to perform this function.
Cardiac muscle cells are smaller than skeletal muscles, averaging 10–20 mm in diameter and 50–100 mm in length. However, they have large energy demands for continuous contraction and relaxation. This energy is almost exclusively derived from aerobic metabolism of energy reserves in...