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Simulations of NAADP-dependent junctional Ca 2+ transients demonstrate that the magnitude of these signals can breach the threshold for CICR via RyR3.
Most importantly, our model shows that increasing the L-SR junctional width above 50 nm lowers the magnitude of junctional [Ca 2+] such that there is a failure to breach the threshold for CICR via RyR3.
This comparison underscores the important constraint played by the width of the L-SR junctions and indicates that, unless the membrane separation is kept below about 30 nm, it is not possible for [Ca 2+] NJ to breach the threshold for RyR3 Ca 2+ release.
Even within the variability of our recorded values of L-SR junctional widths and extension, our results suggest that localized [Ca 2+] transients due to junctional Ca 2+ release can without fail reach values required to breach the threshold for CICR from junctional RyR3s.
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