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

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Abstract
Discrete events of Ca2+ 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 Ca2+ release transients, termed Ca2+ sparks, originate from single release channels or multiple channels clustered in close vicinity. Generalizing methods used earlier to describe cell-averaged Ca2+ release, we derived, as a function of space and time, the flux of Ca2+ release that underlies Ca2+ 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 Ca2+ 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 Ca2+ release channels clustered within discrete SR junctional regions.