PDF(Pubmed)
Abstract：
Levosimendan\'s calcium sensitizing effects in heart muscle cells are well established; yet, its potential impact on skeletal muscle cells has not been evidently determined. Despite controversial results, levosimendan is still expected to interact with skeletal muscle through off-target sites (further than troponin C). Adding to this debate, we investigated levosimendan\'s acute impact on fast-twitch skeletal muscle biomechanics in a length-dependent activation study by submersing single muscle fibres in a levosimendan-supplemented solution. We employed our MyoRobot technology to investigate the calcium sensitivity of skinned single muscle fibres alongside their stress-strain response in the presence or absence of levosimendan (100 µM). While control data are in agreement with the theory of length-dependent activation, levosimendan appears to shift the onset of the \'descending limb\' of active force generation to longer sarcomere lengths without notably improving myofibrillar calcium sensitivity. Passive stretches in the presence of levosimendan yielded over twice the amount of enlarged restoration stress and Young\'s modulus in comparison to control single fibres. Both effects have not been described before and may point towards potential off-target sites of levosimendan.
摘要：
左西孟旦在心肌细胞中的钙致敏作用已得到证实；然而，其对骨骼肌细胞的潜在影响尚未明确。尽管结果有争议，左西孟旦仍有望通过脱靶部位与骨骼肌相互作用（比肌钙蛋白C更进一步）。除了这场辩论，在一项长度依赖性激活研究中,我们通过将单根肌纤维浸入补充左西孟旦的溶液中,研究了左西孟旦对快速抽搐骨骼肌生物力学的急性影响.我们采用MyoRobot技术研究了在存在或不存在左西孟旦（100µM）的情况下，皮肤单根肌肉纤维的钙敏感性以及它们的应力应变响应。虽然控制数据与长度依赖性激活理论一致，左西孟旦似乎将主动力产生的“下降肢”的开始转移到更长的肌节长度，而没有显着改善肌原纤维钙敏感性。与对照单纤维相比，在左西孟旦存在下的被动拉伸产生了两倍以上的扩大的恢复应力和杨氏模量。这两种作用以前都没有描述过，可能指向左西孟旦的潜在脱靶位点。
