Department of Anesthesiology Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
J Biol Chem. 2010 Apr 30;285(18):13781-7. doi: 10.1074/jbc.M110.107300. Epub 2010 Mar 5.
The control of resting free Ca(2+) in skeletal muscle is thought to be a balance of channels, pumps, and exchangers in both the sarcolemma and sarcoplasmic reticulum. We explored these mechanisms using pharmacologic and molecular perturbations of genetically engineered (dyspedic) muscle cells that constitutively lack expression of the skeletal muscle sarcoplasmic reticulum Ca(2+) release channels, RyR1 and RyR3. We demonstrate here that expression of RyR1 is responsible for more than half of total resting Ca(2+) concentration (Ca(2+)) measured in wild type cells. The elevated Ca(2+) in RyR1-expressing cells is not a result of active gating of the RyR1 channel but instead is accounted for by the RyR1 ryanodine-insensitive Ca(2+) leak conformation. In addition, we demonstrate that basal sarcolemmal Ca(2+) influx is also governed by RyR1 expression and contributes in the regulation of Ca(2+) in skeletal myotubes.
骨骼肌中静息游离 Ca(2+)的控制被认为是肌膜和肌浆网中通道、泵和交换器的平衡。我们使用遗传工程（dyspedic）肌肉细胞的药理学和分子扰动来探索这些机制，这些细胞持续缺乏骨骼肌肌浆网 Ca(2+)释放通道 RyR1 和 RyR3 的表达。我们在这里证明，RyR1 的表达负责测量野生型细胞中超过一半的总静息 Ca(2+)浓度(Ca(2+))。RyR1 表达细胞中升高的Ca(2+)不是 RyR1 通道主动门控的结果，而是由 RyR1 ryanodine 不敏感的 Ca(2+)泄漏构象解释的。此外，我们还证明，基础肌膜 Ca(2+)内流也受 RyR1 表达的控制，并有助于调节骨骼肌肌管中的Ca(2+)。
