Yamamoto S, Tsutsui H, Takahashi M, Ishibashi Y, Tagawa H, Imanaka-Yoshida K, Saeki Y, Takeshita A
Faculty of Medicine, Kyushu University School of Medicine, Fukuoka, 812-8582, Japan.
J Mol Cell Cardiol. 1998 Sep;30(9):1841-53. doi: 10.1006/jmcc.1998.0747.
Myocardial viscoelastic properties are determined by both interstitial collagens and intramocyte structures, including sarcolemma, contractile proteins and the cytoskeleton. It is not known whether myocyte microtubules are significant constituents that contribute to the viscoelastic properties of cardiac muscle. We examined the passive properties of isolated right-ventricular papillary muscles before and after altering the polymerization states of microtubules. The muscles were subjected to sinusoidal changes in length (strain) and the resultant changes in resting tension (stress) were measured. The elastic constant was determined by the slope of the stress-strain relation during the slow increase in muscle length (duration 60 s). The viscous constant was determined by the loop area between the stress-strain relation obtained during the rapid increase and decrease in muscle length (duration 1 s). Colchicine (1 micromol/l, 1 h), which depolymerized microtubules, had little effect on either the elastic constant or viscous constant. In contrast, taxol (10 micromol/l), which hyperpolymerized and stabilized microtubules, exerted a time-dependent increase in the viscous constant (133+/-9% of control; n=9, P<0.05), but did not affect the elastic constant (18. 9+/-2.2 to 17.7+/-2.1; n=7, P=n.s.). The increase of viscosity by taxol closely paralleled the increase in the strain rate. The specificity of each pharmacological intervention for the microtubule polymerization state was confirmed by both a Western blot analysis and the immunofluorescence micrographs of myocyte tubulin. Like other cytoskeleton and extracellular collagens, the increase in the myocyte microtubule density was able to modify the viscous component of the passive properties of the isolated cardiac muscle.
心肌的粘弹性特性由细胞间质胶原蛋白和细胞内结构共同决定,细胞内结构包括肌膜、收缩蛋白和细胞骨架。目前尚不清楚心肌细胞微管是否是有助于心肌粘弹性特性的重要组成部分。我们在改变微管聚合状态前后,检测了分离的右心室乳头肌的被动特性。使肌肉长度(应变)呈正弦变化,并测量由此产生的静息张力(应力)变化。弹性常数由肌肉长度缓慢增加(持续60秒)期间应力-应变关系的斜率确定。粘性常数由肌肉长度快速增加和减少(持续1秒)期间获得的应力-应变关系之间的环路面积确定。使微管解聚的秋水仙碱(1微摩尔/升,1小时)对弹性常数或粘性常数几乎没有影响。相比之下,使微管过度聚合并稳定的紫杉醇(10微摩尔/升)使粘性常数随时间增加(为对照的133±9%;n = 9,P < 0.05),但不影响弹性常数(从18.9±2.2变为17.7±2.1;n = 7,P = 无显著差异)。紫杉醇引起的粘度增加与应变率增加密切平行。通过蛋白质免疫印迹分析和心肌细胞微管蛋白的免疫荧光显微照片,证实了每种药物干预对微管聚合状态的特异性。与其他细胞骨架和细胞外胶原蛋白一样,心肌细胞微管密度的增加能够改变分离心肌被动特性的粘性成分。