Termination of Cardiac Ca2+ Sparks: Role of Intra-SR [Ca2+], Release Flux, and Intra-SR Ca2+ Diffusion. Export

@article{citeulike:3561616, abstract = {Abstract—Ca2
release from cardiac sarcoplasmic reticulum (SR) via ryanodine receptors (RyRs) is regulated by dyadic cleft [Ca2
] and intra-SR free [Ca2
] ([Ca2
]SR). Robust SR Ca2
release termination is important for stable excitation– contraction coupling, and partial [Ca2
]SR depletion may contribute to release termination. Here, we investigated the regulation of SR Ca2
release termination of spontaneous local SR Ca2
release events (Ca2
sparks) by [Ca2
]SR, release flux, and intra-SR Ca2
diffusion. We simultaneously measured Ca2
sparks and Ca2
blinks (localized elementary [Ca2
]SR depletions) in permeabilized ventricular cardiomyocytes over a wide range of SR Ca2
loads and release fluxes. Sparks terminated via a [Ca2
]SR-dependent mechanism at a fixed [Ca2
]SR depletion threshold independent of the initial [Ca2
]SR and release flux. Ca2
blink recovery depended mainly on intra-SR Ca2
diffusion rather than SR Ca2
uptake. Therefore, the large variation in Ca2
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 Ca2
release and [Ca2
]SR refilling reached a balance, preventing [Ca2
]SR from depleting to the termination threshold. Prolonged release events eventually terminated at a steady [Ca2
]SR, indicative of a slower, [Ca2
]SR-independent termination mechanism. These results demonstrate that there is high variability in local SR connectivity but that SR Ca2
release terminates at a fixed [Ca2
]SR termination threshold. Thus, reliable SR Ca2
release termination depends on tight RyR regulation by [Ca2
]SR. (Circ Res. 2008;103:e105-e115.)}, author = {Zima, Aleksey V. and Picht, Eckard and Bers, Donald M. and Blatter, Lothar A.}, citeulike-article-id = {3561616}, journal = {Circulation Research}, keywords = {ca-blinks, ca-diffusion, fluo5n, magnesium, permeabilized-myocytes, rabbit, spark-amplitude, spark-rate, spark-size, spark-termination, sr-depletion, sr-load, sr-loading, sr-release-flux, tetracaine}, pages = {e105--e115}, posted-at = {2008-11-17 20:08:11}, priority = {0}, title = {Termination of Cardiac Ca2+ Sparks: Role of Intra-SR [Ca2+], Release Flux, and Intra-SR Ca2+ Diffusion.}, volume = {103}, year = {2008} }

TY - JOUR ID - citeulike:3561616 L3 - citeulike-article-id:3561616 N2 - Abstract—Ca2
release from cardiac sarcoplasmic reticulum (SR) via ryanodine receptors (RyRs) is regulated by dyadic cleft [Ca2
] and intra-SR free [Ca2
] ([Ca2
]SR). Robust SR Ca2
release termination is important for stable excitation– contraction coupling, and partial [Ca2
]SR depletion may contribute to release termination. Here, we investigated the regulation of SR Ca2
release termination of spontaneous local SR Ca2
release events (Ca2
sparks) by [Ca2
]SR, release flux, and intra-SR Ca2
diffusion. We simultaneously measured Ca2
sparks and Ca2
blinks (localized elementary [Ca2
]SR depletions) in permeabilized ventricular cardiomyocytes over a wide range of SR Ca2
loads and release fluxes. Sparks terminated via a [Ca2
]SR-dependent mechanism at a fixed [Ca2
]SR depletion threshold independent of the initial [Ca2
]SR and release flux. Ca2
blink recovery depended mainly on intra-SR Ca2
diffusion rather than SR Ca2
uptake. Therefore, the large variation in Ca2
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 Ca2
release and [Ca2
]SR refilling reached a balance, preventing [Ca2
]SR from depleting to the termination threshold. Prolonged release events eventually terminated at a steady [Ca2
]SR, indicative of a slower, [Ca2
]SR-independent termination mechanism. These results demonstrate that there is high variability in local SR connectivity but that SR Ca2
release terminates at a fixed [Ca2
]SR termination threshold. Thus, reliable SR Ca2
release termination depends on tight RyR regulation by [Ca2
]SR. (Circ Res. 2008;103:e105-e115.) JF - Circulation Research EP - e115 TI - Termination of Cardiac Ca2+ Sparks: Role of Intra-SR [Ca2+], Release Flux, and Intra-SR Ca2+ Diffusion. VL - 103 SP - e105 KW - ca-blinks KW - ca-diffusion KW - fluo5n KW - magnesium KW - permeabilized-myocytes KW - rabbit KW - spark-amplitude KW - spark-rate KW - spark-size KW - spark-termination KW - sr-depletion KW - sr-load KW - sr-loading KW - sr-release-flux KW - tetracaine AU - Zima, Aleksey AU - Picht, Eckard AU - Bers, Donald AU - Blatter, Lothar PY - 2008/// ER -