Calcium sparks.

The calcium ion (Ca(2+)) is the simplest and most versatile intracellular messenger known. The discovery of Ca(2+) sparks and a related family of elementary Ca(2+) signaling events has revealed fundamental principles of the Ca(2+) signaling system. A newly appreciated "digital" subsystem consisting of brief, high Ca(2+) concentration over short distances (nanometers to microns) comingles with an "analog" global Ca(2+) signaling subsystem. Over the past 15 years, much has been learned about the theoretical and practical aspects of spark formation and detection. The quest for the spark mechanisms [the activation, coordination, and termination of Ca(2+) release units (CRUs)] has met unexpected challenges, however, and raised vexing questions about CRU operation in situ. Ample evidence shows that Ca(2+) sparks catalyze many high-threshold Ca(2+) processes involved in cardiac and skeletal muscle excitation-contraction coupling, vascular tone regulation, membrane excitability, and neuronal secretion. Investigation of Ca(2+) sparks in diseases has also begun to provide novel insights into hypertension, cardiac arrhythmias, heart failure, and muscular dystrophy. An emerging view is that spatially and temporally patterned activation of the digital subsystem confers on intracellular Ca(2+) signaling an exquisite architecture in space, time, and intensity, which underpins signaling efficiency, stability, specificity, and diversity. These recent advances in "sparkology" thus promise to unify the simplicity and complexity of Ca(2+) signaling in biology.