Gregorevic Paul, Plant David R, Stupka Nicole, Lynch Gordon S
Department of Physiology, The University of Melbourne, Victoria 3010, Australia.
J Physiol. 2004 Jul 15;558(Pt 2):549-60. doi: 10.1113/jphysiol.2004.066217. Epub 2004 Jun 4.
Damaged skeletal muscle fibres are replaced with new contractile units via muscle regeneration. Regenerating muscle fibres synthesize functionally distinct isoforms of contractile and regulatory proteins but little is known of their functional properties during the regeneration process. An advantage of utilizing single muscle fibre preparations is that assessment of their function is based on the overall characteristics of the contractile apparatus and regulatory system and as such, these preparations are sensitive in revealing not only coarse, but also subtle functional differences between muscle fibres. We examined the Ca(2+)- and Sr(2+)-activated contractile characteristics of permeabilized fibres from rat fast-twitch (extensor digitorum longus) and slow-twitch (soleus) muscles at 7, 14 and 21 days following myotoxic injury, to test the hypothesis that fibres from regenerating fast and slow muscles have different functional characteristics to fibres from uninjured muscles. Regenerating muscle fibres had approximately 10% of the maximal force producing capacity (P(o)) of control (uninjured) fibres, and an altered sensitivity to Ca(2+) and Sr(2+) at 7 days post-injury. Increased force production and a shift in Ca(2+) sensitivity consistent with fibre maturation were observed during regeneration such that P(o) was restored to 36-45% of that in control fibres by 21 days, and sensitivity to Ca(2+) and Sr(2+) was similar to that of control (uninjured) fibres. The findings support the hypothesis that regenerating muscle fibres have different contractile activation characteristics compared with mature fibres, and that they adopt properties of mature fast- or slow-twitch muscle fibres in a progressive manner as the regeneration process is completed.
受损的骨骼肌纤维通过肌肉再生被新的收缩单元所替代。再生的肌纤维会合成功能上不同的收缩蛋白和调节蛋白异构体,但在再生过程中它们的功能特性却鲜为人知。利用单根肌纤维制剂的一个优势在于,对其功能的评估基于收缩装置和调节系统的整体特征,因此,这些制剂不仅能敏锐地揭示肌纤维之间明显的功能差异,还能发现细微的功能差异。我们检测了大鼠快肌(趾长伸肌)和慢肌(比目鱼肌)在肌毒性损伤后7天、14天和21天,经通透处理的肌纤维对Ca(2+)和Sr(2+)激活的收缩特性,以验证再生的快肌和慢肌纤维与未损伤肌肉纤维具有不同功能特性这一假说。再生的肌纤维在损伤后7天时,其最大产力能力(P(o))约为对照(未损伤)纤维的10%,且对Ca(2+)和Sr(2+)的敏感性发生了改变。在再生过程中观察到产力增加以及Ca(2+)敏感性的变化,这与纤维成熟一致,以至于到21天时P(o)恢复到对照纤维的36 - 45%,并且对Ca(2+)和Sr(2+)的敏感性与对照(未损伤)纤维相似。这些发现支持了这样的假说:与成熟纤维相比,再生的肌纤维具有不同的收缩激活特性,并且随着再生过程的完成,它们会逐渐呈现成熟快肌或慢肌纤维的特性。