Ca 2+ Waves During Triggered Propagated Contractions in Intact Trabeculae

Abstract
—During triggered propagated contractions, Ca 2+ waves travel along cardiac trabeculae with a constant velocity (V prop ) ranging from 0.34 to 5.47 mm/s. To explore the determinants of V prop , we studied (1) the relationship between [Ca 2+ ] i and V prop and (2) the effect of low concentrations of caffeine on V prop . Trabeculae were dissected from the right ventricle of rat hearts. [Ca 2+ ] i was measured using electrophoretically injected fura-2 and an image-intensified CCD camera. Force was measured using a silicon strain gauge, and sarcomere length was measured using laser diffraction techniques. After induction of reproducible Ca 2+ waves by trains of electrical stimuli (2.5 Hz) at 21.9±0.2°C, the number of stimuli or [Ca 2+ ] o was varied in 9 trabeculae. In 5 trabeculae, the effects of caffeine (0.1 to 1.0 mmol/L) at [Ca 2+ ] o of 2.2±0.3 mmol/L were determined. All images were recorded under stable conditions of wave propagation. The increment in [Ca 2+ ] i during the last electrically stimulated transient (ΔCa T ) and [Ca 2+ ] i just before onset of the Ca 2+ waves (Ca D ) were used to estimate the Ca 2+ loading of the sarcoplasmic reticulum (SR) and the myoplasm, respectively. The ratio (ΔCa W /ΔCa T ) of the [Ca 2+ ] i increment during the waves (ΔCa W ) to ΔCa T was used to estimate the probability of opening of the SR-Ca 2+ release channel during wave propagation. As a result of an increase of the number of stimuli or [Ca 2+ ] o , V prop increased in proportion to (1) ΔCa T ( r =0.82); (2) Ca D ( r =0.88); (3) ΔCa W ( r =0.85); and (4) ΔCa W /ΔCa T ( r =0.74). The addition of caffeine (≤0.3 mmol/L) increased V prop for any ΔCa T and any ΔCa W , revealing an increased sensitivity of V prop to ΔCa T and ΔCa W . In contrast, caffeine had little effect on the relationship between V prop and Ca D and no effect on that between V prop and ΔCa W /ΔCa T . These results suggest that both the cellular Ca 2+ loading and open probability of the SR-Ca 2+ release channels determine the velocity of propagation of Ca 2+ waves.