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

Masahito Miura, Yuhto Taguchi, Tsuyoshi Nagano, Mai Sasaki, Tetsuya Handoh, Chiyohiko Shindoh

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

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+]i were measured. ROS production was estimated from 2',7'-dichlorofluorescein (DCF) fluorescence. Trabeculae were exposed to a 10mM 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 7.5s (24°C, 2.0mM [Ca2+]o). Muscle stretch of 5, 10, and 15% was applied 300ms 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 3μM diphenyleneiodonium (DPI), muscle stretch increased only the amplitude of aftercontractions but not the DCF fluorescence nor the velocity of Ca2+ waves. SCH00013 (30μM) 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.

Original languageEnglish
Pages (from-to)162-169
Number of pages8
JournalJournal of Molecular and Cellular Cardiology
Volume84
DOIs
Publication statusPublished - 2015 Jul 1

Keywords

  • Ca waves
  • Muscle stretch
  • Myofilament Ca sensitivity
  • ROS

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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