Luin Elisa, Lorenzon Paola, Wernig Anton, Ruzzier Fabio
Department of Physiology and Pathology, University of Trieste, Via A. Fleming 22, I-34127 Trieste, Italy.
Cell Calcium. 2008 Dec;44(6):554-66. doi: 10.1016/j.ceca.2008.04.002. Epub 2008 May 23.
There is evidence that the complex process of sarcopenia in human aged skeletal muscle is linked to the modification of mechanisms controlling Ca(2+) homeostasis. To further clarify this issue, we assessed the changes in the kinetics of activation and inactivation of T- and L-type Ca(2+) currents in in vitro differentiated human myotubes, derived from satellite cells of healthy donors aged 2, 12, 76 and 86 years. The results showed an age-related decrease in the occurrence of T- and L-type currents. Moreover, significant age-dependent alterations were found in L-(but not T) type current density, and activation and inactivation kinetics, although an interesting alteration in the kinetics of T-current inactivation was observed. The T- and L-type Ca(2+) currents play a crucial role in regulating Ca(2+) entry during satellite cells differentiation and fusion into myotubes. Also, the L-type Ca(2+) channels underlie the skeletal muscle excitation-contraction coupling mechanism. Thus, our results support the hypothesis that the aging process could negatively affect the Ca(2+) homeostasis of these cells, by altering Ca(2+) entry through T- and L-type Ca(2+) channels, thereby putting a strain on the ability of human satellite cells to regenerate skeletal muscle in elderly people.
有证据表明，人类老年骨骼肌中肌肉减少症的复杂过程与控制钙（Ca2+）稳态机制的改变有关。为了进一步阐明这个问题，我们评估了从2岁、12岁、76岁和86岁健康供体的卫星细胞体外分化而来的人肌管中T型和L型钙电流激活和失活动力学的变化。结果显示，T型和L型电流的发生率随年龄增长而降低。此外，虽然观察到T电流失活动力学有有趣的变化，但在L型（而非T型）电流密度、激活和失活动力学方面发现了显著的年龄依赖性改变。T型和L型钙电流在卫星细胞分化和融合成肌管过程中调节钙内流方面起着关键作用。此外，L型钙通道是骨骼肌兴奋-收缩偶联机制的基础。因此，我们的结果支持这样一种假设，即衰老过程可能通过改变通过T型和L型钙通道的钙内流，对这些细胞的钙稳态产生负面影响，从而给老年人中人类卫星细胞再生骨骼肌的能力带来压力。
