Calsequestrin: more than 'only' a luminal Ca2+ buffer inside the sarcoplasmic reticulum.
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.
Szegedi
C
C
Department of Physiology, University Medical School, H-4012 Debrecen, Hungary.
Sárközi
S
S
Herzog
A
A
Jóna
I
I
Varsányi
M
M
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002155:Calsequestrin / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D010766:Phosphorylation; D011817:Rabbits; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*
D002155:Calsequestrin; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium