title: Role of reactive oxygen species and Ca(2+) dissociation from the myofilaments in determination of Ca(2+) wave propagation in rat cardiac muscle.
abstract: Ca(2+) waves are initiated not only by Ca(2+) leak from the sarcoplasmic reticulum (SR), but also by Ca(2+) dissociation from the myofilaments in the myocardium with nonuniform contraction. We investigated whether contractile properties and the production of reactive oxygen species (ROS) affect Ca(2+) wave propagation. Trabeculae were obtained from 76 rat hearts. Force was measured with a strain gauge, sarcomere length with a laser diffraction technique, and [Ca(2+)](i) with fura-2 and a CCD camera (24°C, 2.0mmol/L [Ca(2+)](o)). ROS production was estimated from 2',7'-dichlorofluorescein (DCF) fluorescence. Trabeculae were regionally exposed to a jet of solution containing 1) 10mmol/L Ca(2+) to initiate Ca(2+) waves by SR Ca(2+) leak due to Ca(2+) overload within the jet-exposed region, and 2) 0.2mmol/L Ca(2+) or 5mmol/L caffeine to initiate such waves by Ca(2+) dissociation from the myofilaments due to nonuniform contraction. Ca(2+) waves were induced by stimulus trains for 7.5s. Ten-percent muscle stretch increased DCF fluorescence and accelerated Ca(2+) waves initiated due to both Ca(2+) overload and nonuniform contraction. Preincubation with 3μmol/L diphenyleneiodonium or 10μmol/L colchicine suppressed the increase in DCF fluorescence but suppressed acceleration of Ca(2+) waves initiated only due to Ca(2+) overload. Irrespective of preincubation with colchicine, reduction of force after the addition of 10μmol/L blebbistatin did not decelerate Ca(2+) waves initiated due to Ca(2+) overload, while it did decelerate waves initiated due to nonuniform contraction. These results suggest that Ca(2+) wave propagation is modulated by ROS production through an intact microtubule network only during stretch and may be additionally modulated by Ca(2+) dissociated from the myofilaments in the case of nonuniform contraction.
authors.affiliation: Department of Clinical Physiology, Health Science, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan. mmiura@med.tohoku.ac.jp
authors.forename: Masahito
authors.initials: M
authors.lastname: Miura
authors.forename: Naomi
authors.initials: N
authors.lastname: Murai
authors.forename: Taiki
authors.initials: T
authors.lastname: Hattori
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Nagano
authors.forename: Bruno D
authors.initials: BD
authors.lastname: Stuyvers
authors.forename: Chiyohiko
authors.initials: C
authors.lastname: Shindoh
mesh_terms: D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D020013:Calcium Signaling; D002478:Cells, Cultured; D003078:Colchicine / Q000494:pharmacology; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D009210:Myofibrils / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D050257:Tubulin Modulators / Q000494:pharmacology
chemical_list: D006576:Heterocyclic Compounds, 4 or More Rings; D017382:Reactive Oxygen Species; D050257:Tubulin Modulators; C472645:blebbistatin; D002110:Caffeine; D003078:Colchicine