Dynamical instability is a major cause of cardiac action potential variability

Area of Science:

• Cardiac Electrophysiology
• Computational Biology
• Arrhythmogenesis Research

Background:

• Increased beat-to-beat QT interval variability (QTV) is linked to sudden cardiac death.
• The underlying mechanisms of QTV, distinct from heart rate variability, are not fully understood.
• Stochastic ion channel gating is a potential source of cardiac variability, but large numbers of channels should minimize this effect.

Purpose of the Study:

• To test the hypothesis that dynamical instability amplifies stochastic ion channel fluctuations, causing action potential (AP) variability.
• To investigate the relationship between AP variability and voltage instability in ventricular myocytes.
• To provide a mechanistic explanation for increased QTV in pathological conditions.

Main Methods:

• Utilized a mathematical model of ventricular myocytes.
• Investigated the correlation between AP duration variability and voltage instability, quantified by the AP duration restitution curve slope.
• Analyzed variability considering every other beat to identify the onset of alternans.

Main Results:

• Stochastic gating alone was insufficient to produce significant AP variability.
• Dynamical instability was found to significantly amplify stochastic fluctuations, leading to increased AP variability.
• A positive correlation was observed between voltage instability and AP duration variability, with maximum variability at the onset of alternans.

Conclusions:

• Dynamical instability plays a critical role in amplifying ion channel stochasticity, driving cardiac electrical variability.
• This mechanism offers a new explanation for increased QTV in disease states.
• Measuring QTV, particularly every other beat, may serve as a predictor for alternans and arrhythmia risk.