Abstract 13630: Regional Ros Production Causes Ca2+ Waves in the Myocardium with Nonuniform Contraction
Introduction: In diseased hearts, Ca2+ is dissociated from the myofilaments during the relaxation phase due to the paradoxical shortening of the impaired muscle by relaxation of the more viable neighboring muscle. This dissociated Ca2+ initiates Ca2+ waves from the border zone (BZ) between the impaired muscle and the viable muscle. It is still unclear, however, why Ca2+ waves can be initiated from the BZ but not from the impaired muscle. We examined whether reactive oxygen species (ROS) production plays a role in their initiation using the myocardium with nonuniform contraction.
Methods: Trabeculae were dissected from rat hearts. Force was measured with a strain gauge, and intracellular Ca2+ (Cai) with fura-2 and a CCD camera. To assess ROS production, the fluorescence of 2’,7’-dichlorofluorescein (DCF) was measured with a CCD camera. Nonuniform contraction was produced by a jet of 2,3-butanedione monoxime (20 mM) solution. Ca2+ waves were induced by stimulation at 400 ms intervals for 7.5 s (24oC, Cao 2.0 mM).
Results: One second after the stoppage of electrical stimulation (4 Hz) for 30 s, the DCF fluorescence was regionally increased only within the contracting region but not within the stretched region of the myocardium with nonuniform contraction (n=8, p<0.05). Five seconds after the stoppage, this regional increase became unclear. After the superfusion of 10 μM diphenyleneiodonium (DPI), a NADPH oxidase inhibitor, this regional increase of the DCF fluorescence after the stimulation did not occur. Also in the myocardium showing “uniform” contraction, this regional increase of the DCF fluorescence did not occur (n=8). After the superfusion of DPI, the velocity of Ca2+ waves was significantly decreased within the contracting region (n=7). In the myocardium arrested by 10 μM blebbistatin, the velocity of Ca2+ waves was increased within the region exposed to a jet of solution containing 1 mM H2O2.
Conclusions: As a result of ROS production within the contracting region, the Ca2+ dissociated from the myofilaments within the stretched region may enhance Ca2+ release from the sarcoplasmic reticulum especially near the contracting region, that is, within the BZ, thereby initiating Ca2+ waves from the BZ in the myocardium showing nonuniform contraction.
Author Disclosures: Y. Taguchi: None. M. Miura: None. Y. Kato: None. T. Hando: None. M. Sasaki: None. C. Shindoh: None.
- © 2014 by American Heart Association, Inc.