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Calcium Sparks

Institute of Molecular Medicine, National Laboratory of Biomembrane and Membrane Biotechnology, Peking University, Beijing, China; and Medical Biotechnology Center, University of Maryland Biotechnology Institute, Baltimore, Maryland

The calcium ion (Ca²⁺) is the simplest and most versatile intracellular messenger known. The discovery of Ca²⁺ sparks and a related family of elementary Ca²⁺ signaling events has revealed fundamental principles of the Ca²⁺ signaling system. A newly appreciated "digital" subsystem consisting of brief, high Ca²⁺ concentration over short distances (nanometers to microns) comingles with an "analog" global Ca²⁺ 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 Ca²⁺ release units (CRUs)] has met unexpected challenges, however, and raised vexing questions about CRU operation in situ. Ample evidence shows that Ca²⁺ sparks catalyze many high-threshold Ca²⁺ processes involved in cardiac and skeletal muscle excitation-contraction coupling, vascular tone regulation, membrane excitability, and neuronal secretion. Investigation of Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ signaling in biology.