Calsequestrin: more than 'only'a luminal Ca2+ buffer inside the sarcoplasmic reticulum

C SZEGEDI, S SÁRKÖZI, A HERZOG, I JÓNA… - Biochemical …, 1999 - portlandpress.com
C SZEGEDI, S SÁRKÖZI, A HERZOG, I JÓNA, M VARSÁNYI
Biochemical Journal, 1999portlandpress.com
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+] …
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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