Key result
Dephosphorylated calsequestrin enhanced the open probability of the RyR channel by approximately 5-fold and increased the mean open time by about 2-fold.
Dephosphorylated calsequestrin selectively regulates Ca2+ release from the sarcoplasmic reticulum by enhancing RyR channel open probability and mean open time.
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Does not yet inform clinical practice; leaves open calsequestrin's role in human Ca2+ dysregulation.
In striated muscle, the sarcoplasmic reticulum (SR) Ca2+ release/ryanodine receptor (RyR) channel provides the pathway through which stored Ca2+ is released into the myoplasm during excitation–contraction coupling. Various luminal Ca2+-binding proteins are responsible for maintaining the free [Ca2+] at 10-3–10-4 M in the SR lumen; in skeletal-muscle SR, it is mainly calsequestrin. Here we show that, depending on its phosphorylation state, calsequestrin selectively controls the RyR channel activity at 1 mM free luminal [Ca2+]. Calsequestrin exclusively in the dephosphorylated state enhanced the open probability by approx. 5-fold with a Hill coefficient (h) of 3.3, and increased the mean open time by about 2-fold, i.e. solely dephosphorylated calsequestrin regulates Ca2+ release from the SR. Because calsequestrin has been found to occur mainly in the phosphorylated state in the skeletal-muscle SR for the regulation of RyR channel activity, the dephosphorylation of calsequestrin would appear to be a quintessential physiological event.
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Szegedi et al. (1999) studied this question. Dephosphorylated calsequestrin vs. Phosphorylated calsequestrin was evaluated on RyR channel open probability and mean open time (approx. 5-fold increase). Dephosphorylated calsequestrin enhanced the open probability of the RyR channel by approximately 5-fold and increased the mean open time by about 2-fold.
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