AI Article Synopsis
- The heart muscle maintains consistent contraction throughout life due to the precise interaction of electrical, chemical, and mechanical elements within the sarcomere, its basic contractile unit.
- Calcium plays a crucial role in muscle contraction by being released at the sarcomere ends and having to diffuse to the center to activate contractile proteins, which could lead to inefficient contraction.
- Myosin-binding protein C (MyBP-C) helps ensure uniform calcium activation by enhancing sensitivity to calcium, and its proper positioning is essential for healthy heart function; any disruption can lead to heart-related diseases.
Article Abstract
The beating heart exhibits remarkable contractile fidelity over a lifetime, which reflects the tight coupling of electrical, chemical, and mechanical elements within the sarcomere, the elementary contractile unit. On a beat-to-beat basis, calcium is released from the ends of the sarcomere and must diffuse toward the sarcomere center to fully activate the myosin- and actin-based contractile proteins. The resultant spatial and temporal gradient in free calcium across the sarcomere should lead to nonuniform and inefficient activation of contraction. We show that myosin-binding protein C (MyBP-C), through its positioning on the myosin thick filaments, corrects this nonuniformity in calcium activation by exquisitely sensitizing the contractile apparatus to calcium in a manner that precisely counterbalances the calcium gradient. Thus, the presence and correct localization of MyBP-C within the sarcomere is critically important for normal cardiac function, and any disturbance of MyBP-C localization or function will contribute to the consequent cardiac pathologies.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380226 | PMC |
| http://dx.doi.org/10.1126/sciadv.1400205 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Rapid changes in plasma corticosterone and medial amygdala transcriptome profiles during social status change reveal molecular pathways associated with a major life history transition in mouse dominance hierarchies.
PLoS Genet
January 2025
Department of Psychology, University of Texas at Austin, Austin, Texas, United States of America.
Social hierarchies are a common form of social organization across species. Although hierarchies are largely stable across time, animals may socially ascend or descend within hierarchies depending on environmental and social challenges. Here, we develop a novel paradigm to study social ascent and descent within male CD-1 mouse social hierarchies.
View Article and Find Full Text PDFHypertrophic cardiomyopathy: insights into pathophysiology and novel therapeutic strategies from clinical studies.
Egypt Heart J
January 2025
Department of Physiology, Faculty of Basic Medical Sciences, Obafemi Awolowo College of Health Sciences, Olabisi Onabanjo University, Sagamu Campus, Sagamu, Ogun State, Nigeria.
Background: Hypertrophic cardiomyopathy (HCM) is a frequently encountered cardiac condition worldwide, often inherited, and characterized by intricate phenotypic and genetic manifestations. The natural progression of HCM is diverse, largely due to mutations in the contractile and relaxation proteins of the heart. These mutations disrupt the normal structure and functioning of the heart muscle, particularly affecting genes that encode proteins involved in the contraction and relaxation of cardiac muscle.
View Article and Find Full Text PDFThe N-Terminal Mutations of cMyBP-C Affect Calcium Regulation, Kinetics, and Force of Muscle Contraction.
Int J Mol Sci
December 2024
Institute of Immunology and Physiology, Russian Academy of Sciences, 620049 Yekaterinburg, Russia.
The cardiac myosin binding protein-C (cMyBP-C) regulates cross-bridge formation and controls the duration of systole and diastole at the whole heart level. As known, mutations in cMyBP-C increase the cross-bridge number and rate of their cycling, hypercontractility, and myocardial hypertrophy. We investigated the effects of the mutations D75N and P161S of cMyBP-C related to hypertrophic cardiomyopathy on the mechanism of force generation in isolated slow skeletal muscle fibers.
View Article and Find Full Text PDFMechanism-based myofilament manipulation to treat diastolic dysfunction in HFpEF.
Front Physiol
December 2024
Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH, United States.
Heart failure with preserved ejection fraction (HFpEF) is a major public health challenge, affecting millions worldwide and placing a significant burden on healthcare systems due to high hospitalization rates and limited treatment options. HFpEF is characterized by impaired cardiac relaxation, or diastolic dysfunction. However, there are no therapies that directly treat the primary feature of the disease.
View Article and Find Full Text PDFBackground: Hypertrophic cardiomyopathy (HCM) is a common heritable heart disease where the most frequently associated mutations occur in the myosin-binding protein C () sarcomere-associated gene. HCM is also a common veterinary clinical problem in certain cat breeds such as Maine Coons and Ragdolls, also most associated with mutations in . Mouse models of HCM in which mutations are introduced recapitulate some, but not all, features of human HCM.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!