Abstract：
Store-operated Ca2+ entry (SOCE) is a mechanism that allows muscle fibers to recover external Ca2+, which first enters the cytoplasm and then, via SERCA pump, also refills the depleted intracellular stores (i.e., the sarcoplasmic reticulum, SR). We recently discovered that SOCE is mediated by Calcium Entry Units (CEUs), intracellular junctions formed by: (i) SR stacks containing STIM1; and (ii) I-band extensions of the transverse tubule (TT) containing Orai1. The number and size of CEUs increase during prolonged muscle activity, though the mechanisms underlying exercise-dependent formation of new CEUs remain to be elucidated. Here, we first subjected isolated extensor digitorum longus (EDL) muscles from wild type mice to an ex vivo exercise protocol and verified that functional CEUs can assemble also in the absence of blood supply and innervation. Then, we evaluated whether parameters that are influenced by exercise, such as temperature and pH, may influence the assembly of CEUs. Results collected indicate that higher temperature (36 °C vs. 25 °C) and lower pH (7.2 vs. 7.4) increase the percentage of fibers containing SR stacks, the n. of SR stacks/area, and the elongation of TTs at the I band. Functionally, assembly of CEUs at higher temperature (36 °C) or at lower pH (7.2) correlates with increased fatigue resistance of EDL muscles in the presence of extracellular Ca2+. Taken together, these results indicate that CEUs can assemble in isolated EDL muscles and that temperature and pH are two of the possible regulators of CEU formation.
摘要：
储存操作的Ca2+进入（SOCE）是一种允许肌纤维恢复外部Ca2+的机制，首先进入细胞质，然后，通过SERCA泵，还补充耗尽的细胞内储存(即，肌浆网，SR).我们最近发现SOCE是由钙进入单位(CEU)介导的，通过以下方式形成的细胞内连接：（i）包含STIM1的SR堆叠；（ii）包含Orai1的横向小管（TT）的I带延伸。在长时间的肌肉活动期间，CEU的数量和大小增加，尽管依赖运动形成新CEU的潜在机制仍有待阐明。这里,我们首先对来自野生型小鼠的分离的指长伸肌(EDL)进行离体运动方案,并验证了功能性CEU在没有血液供应和神经支配的情况下也可以组装.然后，我们评估了受锻炼影响的参数，如温度和pH值，可能会影响CEU的组装。收集的结果表明温度较高(36°Cvs.25°C）和更低的pH（7.2vs.7.4)增加含有SR堆叠的纤维的百分比，SR堆栈/区域的n.，以及TTs在I波段的伸长。功能上,在较高温度（36°C）或较低pH（7.2）下，CEU的组装与在细胞外Ca2存在下EDL肌肉的抗疲劳性增加相关。一起来看,这些结果表明，CEU可以在分离的EDL肌肉中组装，温度和pH是CEU形成的两个可能的调节剂。
