%0 Journal Article %1 Zima_2008_105 %A Zima, Aleksey V %A Picht, Eckard %A Bers, Donald M %A Blatter, Lothar A %D 2008 %J Circ Res %K ATPases, Animals; Blockers, Calcium Calcium-Transporting Cardiac, Channel Channel, Diffusion; Fluorescence; Heart Kinetics; Membrane Microscopy, Myocytes, Permeability; Potentials; Rabbits; Receptor Release Reticulum Reticulum, Ryanodine Sarcoplasmic Signaling, Ventricles, drug effects/enzymology/metabolism effects/enzymology/metabolism; effects/metabolism; effects; metabolism; pharmacology; %N 8 %P e105--e115 %R 10.1161/CIRCRESAHA.107.183236 %T Termination of cardiac Ca2+ sparks: role of intra-SR Ca2+, release flux, and intra-SR Ca2+ diffusion. %U http://dx.doi.org/10.1161/CIRCRESAHA.107.183236 %V 103 %X Ca(2+) release from cardiac sarcoplasmic reticulum (SR) via ryanodine receptors (RyRs) is regulated by dyadic cleft Ca(2+) and intra-SR free Ca(2+) (Ca(2+)(SR)). Robust SR Ca(2+) release termination is important for stable excitation-contraction coupling, and partial Ca(2+)(SR) depletion may contribute to release termination. Here, we investigated the regulation of SR Ca(2+) release termination of spontaneous local SR Ca(2+) release events (Ca(2+) sparks) by Ca(2+)(SR), release flux, and intra-SR Ca(2+) diffusion. We simultaneously measured Ca(2+) sparks and Ca(2+) blinks (localized elementary Ca(2+)(SR) depletions) in permeabilized ventricular cardiomyocytes over a wide range of SR Ca(2+) loads and release fluxes. Sparks terminated via a Ca(2+)(SR)-dependent mechanism at a fixed Ca(2+)(SR) depletion threshold independent of the initial Ca(2+)(SR) and release flux. Ca(2+) blink recovery depended mainly on intra-SR Ca(2+) diffusion rather than SR Ca(2+) uptake. Therefore, the large variation in Ca(2+) blink recovery rates at different release sites occurred because of differences in the degree of release site interconnection within the SR network. When SR release flux was greatly reduced, long-lasting release events occurred from well-connected junctions. These junctions could sustain release because local SR Ca(2+) release and Ca(2+)(SR) refilling reached a balance, preventing Ca(2+)(SR) from depleting to the termination threshold. Prolonged release events eventually terminated at a steady Ca(2+)(SR), indicative of a slower, Ca(2+)(SR)-independent termination mechanism. These results demonstrate that there is high variability in local SR connectivity but that SR Ca(2+) release terminates at a fixed Ca(2+)(SR) termination threshold. Thus, reliable SR Ca(2+) release termination depends on tight RyR regulation by Ca(2+)(SR).

@article{Zima_2008_105, abstract = {Ca(2+) release from cardiac sarcoplasmic reticulum (SR) via ryanodine receptors (RyRs) is regulated by dyadic cleft [Ca(2+)] and intra-SR free [Ca(2+)] ([Ca(2+)](SR)). Robust SR Ca(2+) release termination is important for stable excitation-contraction coupling, and partial [Ca(2+)](SR) depletion may contribute to release termination. Here, we investigated the regulation of SR Ca(2+) release termination of spontaneous local SR Ca(2+) release events (Ca(2+) sparks) by [Ca(2+)](SR), release flux, and intra-SR Ca(2+) diffusion. We simultaneously measured Ca(2+) sparks and Ca(2+) blinks (localized elementary [Ca(2+)](SR) depletions) in permeabilized ventricular cardiomyocytes over a wide range of SR Ca(2+) loads and release fluxes. Sparks terminated via a [Ca(2+)](SR)-dependent mechanism at a fixed [Ca(2+)](SR) depletion threshold independent of the initial [Ca(2+)](SR) and release flux. Ca(2+) blink recovery depended mainly on intra-SR Ca(2+) diffusion rather than SR Ca(2+) uptake. Therefore, the large variation in Ca(2+) blink recovery rates at different release sites occurred because of differences in the degree of release site interconnection within the SR network. When SR release flux was greatly reduced, long-lasting release events occurred from well-connected junctions. These junctions could sustain release because local SR Ca(2+) release and [Ca(2+)](SR) refilling reached a balance, preventing [Ca(2+)](SR) from depleting to the termination threshold. Prolonged release events eventually terminated at a steady [Ca(2+)](SR), indicative of a slower, [Ca(2+)](SR)-independent termination mechanism. These results demonstrate that there is high variability in local SR connectivity but that SR Ca(2+) release terminates at a fixed [Ca(2+)](SR) termination threshold. Thus, reliable SR Ca(2+) release termination depends on tight RyR regulation by [Ca(2+)](SR).}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Zima, Aleksey V and Picht, Eckard and Bers, Donald M and Blatter, Lothar A}, biburl = {https://www.bibsonomy.org/bibtex/23665daf6805d4b4504be66c0f6a0774a/hake}, description = {The whole bibliography file I use.}, doi = {10.1161/CIRCRESAHA.107.183236}, file = {Zima_2008_105.pdf:Zima_2008_105.pdf:PDF}, institution = {Department of Molecular Biophysics and Physiology, Rush University Medical Center, Chicago, IL 60612, USA.}, interhash = {a5117492f11275c292efde03676ad31a}, intrahash = {3665daf6805d4b4504be66c0f6a0774a}, journal = {Circ Res}, keywords = {ATPases, Animals; Blockers, Calcium Calcium-Transporting Cardiac, Channel Channel, Diffusion; Fluorescence; Heart Kinetics; Membrane Microscopy, Myocytes, Permeability; Potentials; Rabbits; Receptor Release Reticulum Reticulum, Ryanodine Sarcoplasmic Signaling, Ventricles, drug effects/enzymology/metabolism effects/enzymology/metabolism; effects/metabolism; effects; metabolism; pharmacology;}, month = Oct, number = 8, pages = {e105--e115}, pdf = {Zima_2008_105.pdf}, pii = {CIRCRESAHA.107.183236}, pmid = {18787194}, timestamp = {2009-06-03T11:21:39.000+0200}, title = {Termination of cardiac Ca2+ sparks: role of intra-SR [Ca2+], release flux, and intra-SR Ca2+ diffusion.}, url = {http://dx.doi.org/10.1161/CIRCRESAHA.107.183236}, volume = 103, year = 2008 }