Ca²⁺ Spark Termination: Inactivation and Adaptation May Be Manifestations of the Same Mechanism

Several perspectives on Ca²⁺ sparks were recently published. A common theme was the importance of defining the mechanisms that terminate local SR Ca²⁺ release. We propose that the time- and Ca²⁺-dependent modal gating behavior of single ryanodine receptor (RyR) channels is the negative control mechanism that terminates local Ca²⁺ 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 Ca²⁺ signaling in heart.

The local Ca²⁺ spark is thought to represent the elementary intracellular Ca²⁺ release unit in adult mammalian cardiac muscle (Cheng et al. 1993, Cheng et al. 1996). Intuitively, the kinetics and geometry of the Ca^2+...