Abstract 12759: Effect of the Affinity of Myofilaments for Ca2+ on Ca2+ Wave Propagation in Intact Rat Cardiac Trabeculae
Background: The propagation velocity (Vp) of Ca2+ waves determines delayed afterdepolarization and affects the occurrence of arrhythmias in cardiac muscle. Muscle stretch causes ROS production by NOX and increases the Vp. We focused on the affinity of myofilaments for Ca2+, investigating whether the Vp shows different responses to changes in the affinity of myofilaments for Ca2+ by stretching muscle or by adding a Ca2+ sensitizer for myofilaments.
Methods: Trabeculae were obtained from 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. Trabeculae were exposed to a jet of solution containing 10 mM Ca2+ for the induction of spontaneous Ca2+ release from the sarcoplasmic reticulum in its exposed region. Ca2+ waves were induced by 2.5-Hz stimulus trains for 7.5 s (24°C, 2.0 mM [Ca2+]o). Muscle stretch for 2 s was applied only during Ca2+ wave propagation 300 ms after the last stimulus of the train.
Results: After preincubation with 3 μM diphenyleneiodonium (DPI), an inhibitor of NOX generation, muscle stretch of 5, 10, and 15% increased the amplitude of aftercontractions (AC) during Ca2+ wave propagation by 37±11 (p≤0.05), 173±28 (p≤0.01), and 356±63% (p≤0.01), respectively, but did not significantly change the Vp of Ca2+ waves (n=12). Despite the difference in the force development, the degree of muscle stretch caused no significant difference in the Vp (n=12, p=0.54). SCH00013 (30 μM), a Ca2+ sensitizer for myofilaments, increased the developed force from 22.0±1.6 to 28.3±1.8 mN/mm2 (n=7, p≤0.01) without changes in [Ca2+]i transients caused by electrical stimuli of 2 s intervals (0.7 mM [Ca2+]o). SCH00013 increased the Vp of Ca2+ waves from 2.0±0.5 to 3.8±0.9 mm/s (n=7, p≤0.05), while it increased the amplitude of AC from 7.1±1.5 to 12.7±2.8 mN/mm2 (n=7, p≤0.01). Preincubation with 3 μM DPI suppressed these increases in Vp (n=8) and AC (n=7).
Conclusions: The affinity of myofilaments for Ca2+ during Ca2+ wave propagation does not affect the Vp of Ca2+ waves, suggesting that it plays a minor role in the occurrence of triggered arrhythmias. In addition, local ROS production by NOX may increase the Vp of Ca2+ waves even though it can increase the affinity of myofilaments for Ca2+.
- © 2013 by American Heart Association, Inc.