title: Effect of myofilament Ca(2+) sensitivity on Ca(2+) wave propagation in rat ventricular muscle.
abstract: 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 7.5s (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.
authors.affiliation: Department of Clinical Physiology, Health Science, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan. Electronic address: mmiura@med.tohoku.ac.jp.
authors.forename: Masahito
authors.initials: M
authors.lastname: Miura
authors.affiliation: Department of Clinical Physiology, Health Science, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.
authors.forename: Yuhto
authors.initials: Y
authors.lastname: Taguchi
authors.affiliation: Department of Clinical Physiology, Health Science, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Nagano
authors.affiliation: Department of Clinical Physiology, Health Science, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Sasaki
authors.affiliation: Department of Clinical Physiology, Health Science, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Handoh
authors.affiliation: Department of Clinical Physiology, Health Science, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.
authors.forename: Chiyohiko
authors.initials: C
authors.lastname: Shindoh
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects; D004095:Dihydropyridines / Q000494:pharmacology; D005452:Fluoresceins / Q000378:metabolism; D005453:Fluorescence; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D009210:Myofibrils / Q000187:drug effects / Q000378:metabolism*; D009861:Onium Compounds / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats
chemical_list: D004095:Dihydropyridines; D005452:Fluoresceins; D009861:Onium Compounds; D011724:Pyridazines; C115124:Sch 00013; C037631:2',7'-dichlorofluorescein; C007517:diphenyleneiodonium; D002118:Calcium
keywords: Ca(2+) waves; Muscle stretch; Myofilament Ca(2+) sensitivity; ROS