Szegedi C, Sárközi S, Herzog A, Jóna I, Varsányi M
Department of Physiology, University Medical School, H-4012 Debrecen, Hungary.
Biochem J. 1999 Jan 1;337 ( Pt 1)(Pt 1):19-22.
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.
在横纹肌中，肌浆网（SR）Ca2+释放/雷诺丁受体（RyR）通道提供了一条途径，通过该途径，储存的Ca2+在兴奋-收缩偶联过程中释放到肌浆中。各种腔Ca2+结合蛋白负责将SR腔内的游离[Ca2+]维持在10（-3）-10（-4）M；在骨骼肌SR中，主要是肌集钙蛋白。在这里我们表明，根据其磷酸化状态，肌集钙蛋白在游离腔[Ca2+]为1 mM时选择性地控制RyR通道活性。仅处于去磷酸化状态的肌集钙蛋白将开放概率提高了约5倍，希尔系数（h）为3.3，并将平均开放时间增加了约2倍，即仅去磷酸化的肌集钙蛋白调节Ca2+从SR的释放。由于已发现肌集钙蛋白在骨骼肌SR中主要以磷酸化状态存在以调节RyR通道活性，因此肌集钙蛋白的去磷酸化似乎是一个典型的生理事件。
