Effect of myofilament Ca(2+) sensitivity on Ca(2+) wave propagation in rat ventricular muscle.

Background: The propagation velocity of Ca(2+) waves determines delayed afterdepolarization and affects the occurrence of triggered arrhythmias in cardiac muscle. We focused on myofilament Ca(2+) sensitivity, investigating how the velocity of Ca(2+) waves responds to its increased sensitivity resulting from muscle stretch or the addition of a myofilament Ca(2+) sensitizer, SCH00013. We further investigated whether production of reactive oxygen species (ROS) may be involved in the change in velocity.

Methods: Trabeculae were obtained from rat hearts. Force, sarcomere length, and [Ca(2+)]i were measured. ROS production was estimated from 2',7'-dichlorofluorescein (DCF) fluorescence. Trabeculae were exposed to a 10 mM Ca(2+) jet for the induction of Ca(2+) leak from the sarcoplasmic reticulum in its exposed region. Ca(2+) waves were induced by 2.5-Hz stimulus trains for 7.5s (24 °C, 2.0 mM [Ca(2+)]o). Muscle stretch of 5, 10, and 15% was applied 300 ms after the last stimulus of the train.

Results: Muscle stretch increased the DCF fluorescence, the amplitude of aftercontractions, and the velocity of Ca(2+) waves depending on the degree of stretch. After preincubation with 3 μM diphenyleneiodonium (DPI), muscle stretch increased only the amplitude of aftercontractions but not the DCF fluorescence nor the velocity of Ca(2+) waves. SCH00013 (30 μM) increased the DCF fluorescence, the amplitude of aftercontractions, and the velocity of Ca(2+) waves. DPI suppressed these increases.

Conclusions: Muscle stretch increases the velocity of Ca(2+) waves by increasing ROS production, not by increasing myofilament Ca(2+) sensitivity. In the case of SCH00013, ROS production increases myofilament Ca(2+) sensitivity and the velocity of Ca(2+) waves. These results suggest that ROS rather than myofilament Ca(2+) sensitivity plays an important role in the determination of the velocity of Ca(2+) waves, that is, arrhythmogenesis.