Granzier H L, Irving T C
Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, Washington State University, Pullman 99164-6520, USA.
Biophys J. 1995 Mar;68(3):1027-44. doi: 10.1016/S0006-3495(95)80278-X.
The passive tension-sarcomere length relation of rat cardiac muscle was investigated by studying passive (or not activated) single myocytes and trabeculae. The contribution of collagen, titin, microtubules, and intermediate filaments to tension and stiffness was investigated by measuring (1) the effects of KCl/KI extraction on both trabeculae and single myocytes, (2) the effect of trypsin digestion on single myocytes, and (3) the effect of colchicine on single myocytes. It was found that over the working range of sarcomeres in the heart (lengths approximately 1.9-2.2 microns), collagen and titin are the most important contributors to passive tension with titin dominating at the shorter end of the working range and collagen at longer lengths. Microtubules made a modest contribution to passive tension in some cells, but on average their contribution was not significant. Finally, intermediate filaments contributed about 10% to passive tension of trabeculae at sarcomere lengths from approximately 1.9 to 2.1 microns, and their contribution dropped to only a few percent at longer lengths. At physiological sarcomere lengths of the heart, cardiac titin developed much higher tensions (> 20-fold) than did skeletal muscle titin at comparable lengths. This might be related to the finding that cardiac titin has a molecular mass of 2.5 MDa, 0.3-0.5 MDa smaller than titin of mammalian skeletal muscle, which is predicted to result in a much shorter extensible titin segment in the I-band of cardiac muscle. Passive stress plotted versus the strain of the extensible titin segment showed that the stress-strain relationships are similar in cardiac and skeletal muscle. The difference in passive stress between cardiac and skeletal muscle at the sarcomere level predominantly resulted from much higher strains of the I-segment of cardiac titin at a given sarcomere length. By expressing a smaller titin isoform, without changing the properties of the molecule itself, cardiac muscle is able to develop significant levels of passive tension at physiological sarcomere lengths.
通过研究被动（或未激活）的单个心肌细胞和肌小梁，对大鼠心肌的被动张力-肌节长度关系进行了研究。通过测量以下内容，研究了胶原蛋白、肌联蛋白、微管和中间丝对张力和硬度的贡献：（1）KCl/KI提取对肌小梁和单个心肌细胞的影响；（2）胰蛋白酶消化对单个心肌细胞的影响；（3）秋水仙碱对单个心肌细胞的影响。发现在心脏肌节的工作范围内（长度约为1.9-2.2微米），胶原蛋白和肌联蛋白是被动张力的最重要贡献者，在工作范围较短的一端肌联蛋白起主导作用，而在较长长度时胶原蛋白起主导作用。微管在一些细胞中对被动张力有适度贡献，但平均而言其贡献并不显著。最后，在肌节长度约为1.9至2.1微米时，中间丝对肌小梁被动张力的贡献约为10%，在更长长度时其贡献降至仅百分之几。在心脏的生理肌节长度下，与同等长度的骨骼肌肌联蛋白相比，心肌肌联蛋白产生的张力要高得多（>20倍）。这可能与以下发现有关：心肌肌联蛋白的分子量为2.5 MDa，比哺乳动物骨骼肌的肌联蛋白小0.3-0.5 MDa，预计这会导致心肌I带中可伸展的肌联蛋白片段短得多。将被动应力与可伸展肌联蛋白片段的应变作图显示，心肌和骨骼肌中的应力-应变关系相似。在肌节水平上，心肌和骨骼肌之间被动应力的差异主要是由于在给定肌节长度下，心肌肌联蛋白I段的应变要高得多。通过表达较小的肌联蛋白异构体，而不改变分子本身的特性，心肌能够在生理肌节长度下产生显著水平的被动张力。
