Integrative systems models of cardiac excitation-contraction coupling.
Summary of "Integrative systems models of cardiac excitation-contraction coupling."
Excitation-contraction coupling in the cardiac myocyte is mediated by a number of highly integrated mechanisms of intracellular Ca(2+) transport. The complexity and integrative nature of heart cell electrophysiology and Ca(2+) cycling has led to an evolution of computational models that have played a crucial role in shaping our understanding of heart function. An important emerging theme in systems biology is that the detailed nature of local signaling events, such as those that occur in the cardiac dyad, have important consequences at higher biological scales. Multiscale modeling techniques have revealed many mechanistic links between microscale events, such as Ca(2+) binding to a channel protein, and macroscale phenomena, such as excitation-contraction coupling gain. Here, we review experimentally based multiscale computational models of excitation-contraction coupling and the insights that have been gained through their application.
Affiliation
Rm 315 Hackerman Hall, 3400 N Charles St, Baltimore MD 21218. rwinslow@jhu.edu.
Journal Details
This article was published in the following journal.
Name: Circulation research
ISSN: 1524-4571
Pages: 70-84
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21212390
- DOI: http://dx.doi.org/10.1161/CIRCRESAHA.110.223578
Medical and Biotech [MESH] Definitions
Ryanodine Receptor Calcium Release Channel
A tetrameric calcium release channel in the SARCOPLASMIC RETICULUM membrane of SMOOTH MUSCLE CELLS, acting oppositely to SARCOPLASMIC RETICULUM CALCIUM-TRANSPORTING ATPASES. It is important in skeletal and cardiac excitation-contraction coupling and studied by using RYANODINE. Abnormalities are implicated in CARDIAC ARRHYTHMIAS and MUSCULAR DISEASES.
Excitation Contraction Coupling
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.
Fendiline
Coronary vasodilator; inhibits calcium function in muscle cells in excitation-contraction coupling; proposed as antiarrhythmic and antianginal agents.
Dantrolene
Skeletal muscle relaxant that acts by interfering with excitation-contraction coupling in the muscle fiber. It is used in spasticity and other neuromuscular abnormalities. Although the mechanism of action is probably not central, dantrolene is usually grouped with the central muscle relaxants.
Systems Theory
Principles, models, and laws that apply to complex interrelationships and interdependencies of sets of linked components which form a functioning whole, a system. Any system may be composed of components which are systems in their own right (sub-systems), such as several organs within an individual organism.
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