Sarcoplasmic reticulum Ca(2+) release flux underlying Ca(2+) sparks in cardiac muscle

Discrete events of Ca(2+) release from the sarcoplasmic reticulum (SR) have been described in cardiac, skeletal, and smooth muscle. In skeletal muscle these release events originate at individual channels. In cardiac muscle, however, it remains a question of debate whether localized Ca(2+) release transients, termed Ca(2+) sparks, originate from single release channels or multiple channels clustered in close vicinity. Generalizing methods used earlier to describe cell-averaged Ca(2+) release, we derived, as a function of space and time, the flux of Ca(2+) release that underlies Ca(2+) sparks. Using the method to analyze spontaneous sparks recorded with confocal microscopy in dissociated cat atrial cells, we obtained in most cases single sparks of Ca(2+) release that appear to originate from approximately 1-μm-wide regions. In many cases, doublets, triplets, and greater groups of release sparks were observed. This multiplicity, the estimated release flux magnitude, and existing data on the structure of junctions between SR and plasmalemma suggest that individual release sparks result from the opening of multiple Ca(2+) release channels clustered within discrete SR junctional regions.