Slow Ca2Â + sparks de-synchronize Ca2Â + release in failing cardiomyocytes: Evidence for altered configuration of Ca2Â + release units?

► Cardiomyocytes from failing hearts exhibit slow, dyssynchronous Ca2 + transients. ► T-tubule disorganization is known to de-synchronize Ca2 + release in failing cells. ► Dyssynchrony additionally results from a subset of Ca2 + sparks with slow kinetics. ► Slow sparks occur at intact dyads, not orphaned ryanodine receptors. ► Slow sparks are predicted to result from reorganization of Ca2 + release units.