Stehle R, Lionne C, Travers F, Barman T
INSERM U 128, CNRS, Montpellier, France.
J Muscle Res Cell Motil. 1998 May;19(4):381-92. doi: 10.1023/a:1005397620720.
We have exploited solvent perturbation to probe the coupling of Ca2+ and rigor activation of the ATPase of myofibrils from rabbit psoas. Three techniques were used: overall myofibrillar ATPases by the rapid-flow quench method; kinetics of the interaction of ATP with myofibrils by fluorescence stopped-flow; and myofibrillar shortening by optical microscopy. Because of its extensive use with muscle systems, ranging from myosin subfragment-1 to muscle fibres, we chose 40% ethylene glycol as the relaxing agent. At 4 degrees C, the glycol had little effect on the myofibrillar ATPase at low [Ca2+], but at high [Ca2+] the activity was reduced 50-fold, close to the level found under relaxing conditions, and there was no shortening. However, the ATPase of chemically cross-linked myofibrils (permanently activated even without Ca2+) was reduced only 3-4-fold. The lesser reduction of the ATPase of permanently activated myofibrils was also observed in single turnover experiments in which activation occurs by a few heads in the rigor state activating the remaining heads. The addition of ADP, which also promotes strong head-thin filament interactions, also activated the ATPase but only in the presence of Ca2+. Further experiments revealed that in 40% ethylene glycol, Ca2+ does initiate shortening but only with the aid of strong interactions and at temperatures above 15 degrees C. This confirms that in the organized and intact myofibril, Ca2+ and rigor activation are coupled, as proposed previously for regulated actomyosin subfragment-1.
我们利用溶剂扰动来探究兔腰大肌肌原纤维中Ca2+与ATP酶的僵硬激活之间的偶联关系。使用了三种技术:通过快速流动淬灭法测定整体肌原纤维ATP酶活性;通过荧光停流法测定ATP与肌原纤维相互作用的动力学;通过光学显微镜观察肌原纤维的缩短情况。由于其在从肌球蛋白亚片段-1到肌纤维等肌肉系统中的广泛应用,我们选择40%的乙二醇作为松弛剂。在4℃时,乙二醇在低[Ca2+]浓度下对肌原纤维ATP酶几乎没有影响,但在高[Ca2+]浓度下,活性降低了50倍,接近松弛条件下的水平,且没有缩短现象。然而,化学交联肌原纤维(即使没有Ca2+也永久激活)的ATP酶活性仅降低了3-4倍。在单周转实验中也观察到永久激活的肌原纤维ATP酶活性降低较少,在该实验中,激活是由处于僵硬状态的少数头部激活其余头部来实现的。添加ADP也能促进头部与细肌丝的强烈相互作用,且仅在Ca2+存在时激活ATP酶。进一步的实验表明,在40%的乙二醇中,Ca2+确实能引发缩短,但仅在强相互作用的帮助下且在温度高于15℃时。这证实了在有组织且完整的肌原纤维中,Ca2+与僵硬激活是偶联的,正如之前对受调节的肌动球蛋白亚片段-1所提出的那样。