Role of reactive oxygen species and Ca2+ dissociation from the myofilaments in determination of Ca2+ wave propagation in rat cardiac muscle

Masahito Miura, Naomi Murai, Taiki Hattori, Tsuyoshi Nagano, Bruno D. Stuyvers, Chiyohiko Shindoh

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Ca2+ waves are initiated not only by Ca2+ leak from the sarcoplasmic reticulum (SR), but also by Ca2+ dissociation from the myofilaments in the myocardium with nonuniform contraction. We investigated whether contractile properties and the production of reactive oxygen species (ROS) affect Ca2+ wave propagation. Trabeculae were obtained from 76 rat hearts. Force was measured with a strain gauge, sarcomere length with a laser diffraction technique, and [Ca2+]i with fura-2 and a CCD camera (24°C, 2.0mmol/L [Ca2+]o). ROS production was estimated from 2',7'-dichlorofluorescein (DCF) fluorescence. Trabeculae were regionally exposed to a jet of solution containing 1) 10mmol/L Ca2+ to initiate Ca2+ waves by SR Ca2+ leak due to Ca2+ overload within the jet-exposed region, and 2) 0.2mmol/L Ca2+ or 5mmol/L caffeine to initiate such waves by Ca2+ dissociation from the myofilaments due to nonuniform contraction. Ca2+ waves were induced by stimulus trains for 7.5s. Ten-percent muscle stretch increased DCF fluorescence and accelerated Ca2+ waves initiated due to both Ca2+ overload and nonuniform contraction. Preincubation with 3μmol/L diphenyleneiodonium or 10μmol/L colchicine suppressed the increase in DCF fluorescence but suppressed acceleration of Ca2+ waves initiated only due to Ca2+ overload. Irrespective of preincubation with colchicine, reduction of force after the addition of 10μmol/L blebbistatin did not decelerate Ca2+ waves initiated due to Ca2+ overload, while it did decelerate waves initiated due to nonuniform contraction. These results suggest that Ca2+ wave propagation is modulated by ROS production through an intact microtubule network only during stretch and may be additionally modulated by Ca2+ dissociated from the myofilaments in the case of nonuniform contraction.

Original languageEnglish
Pages (from-to)97-105
Number of pages9
JournalJournal of Molecular and Cellular Cardiology
Volume56
Issue number1
DOIs
Publication statusPublished - 2013 Mar

Keywords

  • Calcium waves
  • Microtubule
  • Muscle stretch
  • Reactive oxygen species

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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