Termination of Ca2+ release during Ca2+ sparks in rat ventricular myocytes

Confocal Ca 2+ imaging was used to measure spontaneous release events (Ca 2+ sparks) in fluo-3-loaded isolated rat ventricular myocytes. The microscopic Ca 2+ release flux underlying Ca 2+ sparks was derived by adapting the methods used previously to describe macroscopic Ca 2+ release from cell-averaged Ca 2+ transients. The magnitude of the local release fluxes varied from 2 to 5 μ m ms −1 , depending on SR Ca 2+ loading conditions. Following spontaneous activation, the release flux rapidly decayed (τ = 6–12 ms). The rate of termination of release flux was found to be directly related to the magnitude of the flux ( r 2 = 0.88). The rate of termination of local release flux was slowed in the presence of FK506, a compound that is known to reduce inactivation of SR Ca 2+ channels in vitro . These results suggest that termination of release flux during sparks is not due to a spontaneous stochastic decay process or local depletion of Ca 2+ from the SR, but rather involves an active extinguishing mechanism such as Ca 2+ -dependent inactivation or adaptation.