Effects of ryanodine on relaxation in isolated myocardium from different animal species

Relaxation in mammalian ventricular cardiac muscle is sensitive to the prevailing load. This "load dependence of relaxation" (LD) can be demonstrated only when an efficient sarcoplasmic reticulum (SR) is present. To define further the role of the SR in LD, we studied contraction and relaxation in cat, rat and frog cardiac muscle after exposure to ryanodine. Ryanodine is a selective inhibitor of calcium release from the SR. This view was confirmed in the present study in single cardiac rat myocytes with functioning SR. Ryanodine did not affect LD in multicellular mammalian myocardium even though it had already significantly depressed contractility, suggesting that calcium release from the SR plays no role in establishing LD. Calcium accumulation in the SR as a consequence of the inhibited release can account for the late depression of LD in the presence of ryanodine.