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Beat-to-beat repolarization variability in ventricular myocytes and its suppression by electrical coupling
M Zaniboni1, A E Pollard, L Yang
1Department of Evolutive and Functional Biology, University of Parma, Parma, Italy 43100.
Beat-to-beat action potential duration (APD) variability in heart cells is influenced by ion channel behavior. Electrical coupling between myocytes reduces this variability, preventing arrhythmias.
Area of Science:
- Cardiac Electrophysiology
- Computational Biology
- Molecular Cardiology
Background:
- Single ventricular myocytes display beat-to-beat variations in action potential duration (APD) under constant pacing and temperature.
- Understanding the mechanisms of APD variability is crucial for comprehending cardiac rhythm regulation.
Purpose of the Study:
- To quantify beat-to-beat APD variability in single myocytes.
- To investigate the underlying mechanisms of APD variability, including ion channel function and electrotonic interactions.
- To determine the effect of electrotonic coupling on APD variability and arrhythmogenesis.
Main Methods:
- Action potential duration at 90% repolarization (APD90) variability was measured using the coefficient of variability (CV).
- Pharmacological agents like tetrodotoxin (TTX) and EGTA were used to probe ion channel contributions.
- The rapid delayed rectifier potassium current (IKr) was inhibited using L-691,121.
- Electrical coupling between myocytes was simulated using varying junctional resistance (Rj).
Main Results:
- APD90 variability (CV) in normal solution was 2.3 ± 0.9%.
- Extracellular TTX and intracellular EGTA significantly reduced CV by 44% and 26%, respectively, indicating roles for sodium and calcium channels.
- Inhibition of IKr with L-691,121 increased CV by 300%.
- Electrical coupling (Rj = 100 MΩ) reduced CV by 35% and completely abolished early afterdepolarization (EAD) formation in coupled cells.
Conclusions:
- Beat-to-beat APD variability is likely driven by the stochastic behavior of ion channels.
- Electrotonic interactions between myocytes play a significant role in limiting temporal dispersion of refractoriness.
- Reduced APD variability through electrical coupling may serve as a protective mechanism against cardiac arrhythmias.
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