Termination of Ca2+ release during Ca2+ sparks in rat ventricular myocytes.
1. Confocal Ca2+ imaging was used to measure spontaneous release events (Ca2+ sparks) in fluo-3-loaded isolated rat ventricular myocytes. 2. The microscopic Ca2+ release flux underlying Ca2+ sparks was derived by adapting the methods used previously to describe macroscopic Ca2+ release from cell-averaged Ca2+ transients. 3. The magnitude of the local release fluxes varied from 2 to 5 microM ms-1, depending on SR Ca2+ loading conditions. Following spontaneous activation, the release flux rapidly decayed (tau = 6-12 ms). The rate of termination of release flux was found to be directly related to the magnitude of the flux (r2 = 0.88). 4. 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 Ca2+ channels in vitro. 5. These results suggest that termination of release flux during sparks is not due to a spontaneous stochastic decay process or local depletion of Ca2+ from the SR, but rather involves an active extinguishing mechanism such as Ca2+-dependent inactivation or adaptation.
Lukyanenko
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Department of Physiology, Texas Tech University Health Science Center, Lubbock, TX 79430, USA.
Wiesner
T F
TF
Gyorke
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S
D000465:Algorithms; D000814:Aniline Compounds; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005456:Fluorescent Dyes; D006321:Heart / Q000502:physiology*; D006352:Heart Ventricles; D007700:Kinetics; D018613:Microscopy, Confocal; D008956:Models, Chemical; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D016559:Tacrolimus / Q000494:pharmacology; D014966:Xanthenes
D000814:Aniline Compounds; D015220:Calcium Channels; D005456:Fluorescent Dyes; D014966:Xanthenes; C059715:Fluo-3; D002118:Calcium; D016559:Tacrolimus