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Arrhythmogenic Ca(2+) release from cardiac myofilaments
Henk E D J Ter Keurs1, Yuji Wakayama, Masahito Miura
1Department of Medicine, Physiology and Biophysics; University of Calgary Health Science Centre, 3330 Hospital Drive N.W. Calgary, Alta., Canada T2N4N1. terkeurs@ucalgary.ca
Progress in Biophysics and Molecular Biology
|August 27, 2005
Summary
Non-uniform cardiac muscle contraction, induced by simulated damage, triggers calcium waves. These waves, originating from damaged areas, can initiate arrhythmias, especially when calcium levels rise. Restoring uniformity eliminates these abnormal heart rhythms.
Area of Science:
- Cardiac Electrophysiology
- Myocardial Mechanics
- Calcium Signaling
Background:
- Functional non-uniformity in the myocardium, caused by mechanical or ischemic damage, can disrupt normal heart function.
- Understanding the mechanisms behind triggered propagated contractions (TPCs) and associated arrhythmias is crucial for cardiac health.
- Calcium (Ca2+) waves play a central role in excitation-contraction coupling and cardiac arrhythmias.
Purpose of the Study:
- To investigate the initiation of Ca2+ waves underlying TPCs in rat cardiac trabeculae under simulated myocardial non-uniformity.
- To explore the role of myofilament-released Ca2+ in initiating arrhythmogenic Ca2+ waves.
- To model the feedback mechanism between force development and Ca2+ binding to Troponin-C.
Main Methods:
- Created mechanical discontinuity in rat cardiac trabeculae using a localized solution jet affecting excitation-contraction coupling.
- Measured muscle force, sarcomere length, and intracellular Ca2+ ([Ca2+]i) regionally.
- Utilized a four-state cross-bridge model with force feedback to Ca2+ binding by Troponin-C.
Main Results:
- Simulated non-uniformity induced rapid sarcomere shortening during relaxation and triggered Ca2+ waves from damaged borders.
- Ca2+ waves propagated into both normal and damaged segments, initiating non-driven rhythmic activity (arrhythmias) when extracellular Ca2+ ([Ca2+]o) increased.
- The cross-bridge model demonstrated that rapid force decline causes Ca2+ release from Troponin-C, sufficient to trigger arrhythmogenic Ca2+ release.
Conclusions:
- Non-uniform myocardial contraction can initiate Ca2+ waves underlying TPCs.
- Ca2+ dissociation from myofilaments is a key factor in initiating arrhythmogenic Ca2+ waves.
- Feedback mechanisms between force and Ca2+ binding are critical for understanding cardiac arrhythmias.