Ca2+ Spark Termination

Several perspectives on Ca 2 1 sparks were recently published. A common theme was the importance of defining the mechanisms that terminate local SR Ca 2 1 release. We propose that the timeand Ca 2 1 -dependent modal gating behavior of single ryanodine receptor (RyR) channels is the negative control mechanism that terminates local Ca 2 1 release. Specifically, the observed “inactivation” and “adaptation” phenomena are two manifestations of the same general mechanism (i.e., modal RyR gating). We hope this new unified view of RyR negative control mechanisms may lead to new insights into local intracellular Ca 2 1 signaling in heart. The local Ca 2 1 spark is thought to represent the elementary intracellular Ca 2 1 release unit in adult mammalian cardiac muscle (Cheng et al., 1993, 1996). Intuitively, the kinetics and geometry of the Ca 2 1 removal and Ca 2 1 release machinery in the cell govern the spatiotemporal nature of the Ca 2 1 spark. Ryanodine receptor (RyR) channels in the sarcoplasmic reticulum (SR) mediate local intracellular Ca 2 1 release in cardiac muscle (Cheng et al., 1993). The Ca 2 1 spark may arise from the opening of a single ryanodine receptor (RyR) Ca 2 1