The importance of calcium-dependent signaling in the heart has been appreciated for decades. For example, it is well accepted that intracellular calcium release from the sarcoplasmic reticulum (SR) is required for cardiac muscle contraction. Indeed, with each heart beat the calcium concentration in the cytosol of cardiac myocytes is elevated approximately 10-fold from a resting level of∼ 100 nM to∼ 1 µM. Presumably, a defect in signaling that prevents effective elevation of cytosolic calcium would impair contractility as the contraction of heart muscle is directly determined by the level of calcium elevation during systole. Similarly, a defect in the removal of calcium from the cytosol during diastole would impair cardiac relaxation, which is critically important in that it allows the heart chambers to refill with blood in preparation for the next beat.