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 7.5 s (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.