Effect of myofilament Ca2+ sensitivity on Ca2+ wave propagation in rat ventricular muscle

Background: The propagation velocity of Ca2+ waves determines delayed afterdepolarization and affects the occurrence of triggered arrhythmias in cardiac muscle. We focused on myofilament Ca2+ sensitivity, investigating how the velocity of Ca2+ waves responds to its increased sensitivity resulting from muscle stretch or the addition of a myofilament Ca2+ 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 [Ca2+](1) were measured. ROS production was estimated from 2',7'-dichlorofluorescein (DCF) fluorescence. Trabeculae were exposed to a 10 mM Ca2+ jet for the induction of Ca2+ leak from the sarcoplasmic reticulum in its exposed region. Ca2+ waves were induced by 2.5-Hz stimulus trains for 7.5 s (24 degrees C, 2.0 mM [Ca2+](0)). 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 Ca2+ waves depending on the degree of stretch. After preincubation with 3 mu M diphenyleneiodonium (DPI), muscle stretch increased only the amplitude of aftercontractions but not the DCF fluorescence nor the velocity of Ca2+ waves. SCH00013 (30 mu M) increased the DCF fluorescence, the amplitude of aftercontractions, and the velocity of Ca2+ waves. DPI suppressed these increases. Conclusions: Muscle stretch increases the velocity of Ca2+ waves by increasing ROS production, not by increasing myofilament Ca2+ sensitivity. In the case of SCH00013, ROS production increases myofilament Ca2+ sensitivity and the velocity of Ca2+ waves. These results suggest that ROS rather than myofilament Ca2+ sensitivity plays an important role in the determination of the velocity of Ca2+ waves, that is, arrhythmogenesis. (C) 2015 Elsevier Ltd. All rights reserved.