Effect of myofilament Ca2+ sensitivity on Ca2+ wave propagation in rat ventricular muscle
Effect of myofilament Ca2+ sensitivity on Ca2+ wave propagation in rat ventricular muscle
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肌丝Ca2+敏感性对大鼠心室肌Ca2+波传播的影响
DOI：
10.1016/j.yjmcc.2015.04.027
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发表时间：
2015
影响因子：
5
通讯作者：
Shindoh C.
中科院分区：
文献类型：
--
作者：
Miura M;Taguchi Y;Nagano T;Sasaki M;Handoh T;Shindoh C.
Ca2 +波的传播速度决定了延迟后去极化，并影响心肌诱发心律失常的发生。我们专注于肌丝Ca2 +敏感性，研究Ca2 +波的速度如何响应肌肉拉伸或添加肌丝Ca2 +敏化剂SCH00013而增加的敏感性。我们进一步研究了活性氧（ROS）的产生是否可能参与了速度的变化。方法从大鼠心脏中提取骨链。测量力、肌节长度和[Ca2 +]i。通过2 ',7 ' -二氯荧光素（DCF）荧光估计ROS的产生。小梁暴露于10 mM Ca2 +射流中，诱导其暴露区域肌浆网Ca2 +泄漏。2.5 hz刺激序列（24°C, 2.0 mM [Ca2 +]o）持续7.5 s诱导Ca2 +波。在训练最后一次刺激后300 ms，分别进行5%、10%和15%的肌肉拉伸。结果肌肉拉伸使DCF荧光、后收缩幅度和Ca2 +波速度随拉伸程度的增加而增加。3 μM二苯乙烯酮（DPI）预孵育后，肌肉拉伸只增加了后收缩幅度，而没有增加DCF荧光和Ca2 +波的速度。SCH00013 （30 μM）增加了DCF荧光、后收缩幅度和Ca2 +波速度。DPI抑制了这些增长。结论肌肉拉伸增加Ca2 +波的速度是通过增加ROS的产生，而不是通过增加肌丝Ca2 +的敏感性。在SCH00013的情况下，ROS的产生增加了肌丝Ca2 +的敏感性和Ca2 +波的速度。这些结果表明，ROS而不是肌丝Ca2 +敏感性在Ca2 +波速度的决定中起重要作用，即心律失常的发生。
BackgroundThe 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.MethodsTrabeculae were obtained from rat hearts. Force, sarcomere length, and [Ca2 +]iwere 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 °C, 2.0 mM [Ca2 +]o). Muscle stretch of 5, 10, and 15% was applied 300 ms after the last stimulus of the train.ResultsMuscle 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 μM diphenyleneiodonium (DPI), muscle stretch increased only the amplitude of aftercontractions but not the DCF fluorescence nor the velocity of Ca2 +waves. SCH00013 (30 μM) increased the DCF fluorescence, the amplitude of aftercontractions, and the velocity of Ca2 +waves. DPI suppressed these increases.ConclusionsMuscle 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.