O'Connell Kathleen, Gannon Joan, Doran Philip, Ohlendieck Kay
Department of Biology, National University of Ireland, Maynooth, Co. Kildare, Ireland.
Exp Gerontol. 2008 Oct;43(10):958-61. doi: 10.1016/j.exger.2008.07.006. Epub 2008 Aug 14.
In skeletal muscle, Ca(2+)-cycling through the sarcoplasm regulates the excitation-contraction-relaxation cycle. Since uncoupling between sarcolemmal excitation and fibre contraction may play a key role in the functional decline of aged muscle, this study has evaluated the expression levels of key Ca(2+)-handling proteins in senescent preparations using immunoblotting and confocal microscopy. Sarcalumenin, a major luminal Ca(2+)-binding protein that mediates ion shuttling in the longitudinal sarcoplasmic reticulum, was found to be greatly reduced in aged rat tibialis anterior, gastrocnemius and soleus muscle as compared to adult specimens. Minor sarcolemmal components of Ca(2+)-extrusion, such as the surface Ca(2+)-ATPase and the Na(+)-Ca(2+)-exchanger, were also diminished in senescent fibres. No major changes were observed for calsequestrin, sarcoplasmic reticulum Ca(2+)-ATPase and the ryanodine receptor Ca(2+)-release channel. In contrast, the age-dependent reduction in the alpha(1S)-subunit of the dihydropryridine receptor was confirmed. Hence, this report has shown that downstream from the well-established defect in coupling between the t-tubular voltage sensor and the junctional Ca(2+)-release channel complex, additional age-related alterations exist in the expression of essential Ca(2+)-handling proteins. This may trigger abnormal luminal Ca(2+)-buffering and/or decreased plasmalemmal Ca(2+)-removal, which could exacerbate impaired signaling or disturbed intracellular ion balance in aged fibres, thereby causing contractile weakness.
在骨骼肌中，钙离子在肌浆中的循环调节着兴奋 - 收缩 - 舒张周期。由于肌膜兴奋与纤维收缩之间的解偶联可能在衰老肌肉的功能衰退中起关键作用，本研究使用免疫印迹法和共聚焦显微镜评估了衰老标本中关键钙离子处理蛋白的表达水平。肌钙蛋白是一种主要的管腔钙离子结合蛋白，介导纵向肌浆网中的离子穿梭，与成年标本相比，在老年大鼠的胫前肌、腓肠肌和比目鱼肌中发现其含量大幅降低。钙离子外排的次要肌膜成分，如表面钙离子ATP酶和钠 - 钙交换体，在衰老纤维中也减少。对于肌集钙蛋白、肌浆网钙离子ATP酶和兰尼碱受体钙离子释放通道，未观察到重大变化。相比之下，二氢吡啶受体α(1S)亚基随年龄增长而降低得到了证实。因此，本报告表明，在已确定的横管电压传感器与连接钙离子释放通道复合物之间的偶联缺陷的下游，必需钙离子处理蛋白的表达还存在与年龄相关的其他改变。这可能引发管腔钙离子缓冲异常和/或质膜钙离子清除减少，从而加剧衰老纤维中信号传导受损或细胞内离子平衡紊乱，进而导致收缩无力。
