Arner A, Malmqvist U, Rigler R
Department of Physiology and Neuroscience, Lund University, Lund, Sweden. Anders:
Biophys J. 1998 Oct;75(4):1895-903. doi: 10.1016/S0006-3495(98)77630-1.
Intracellular Ca2+ was determined with the fura-2 technique during electrically induced contractions in the rabbit rectococcygeus smooth muscle at 22 degreesC. The muscles were electrically activated to give short, reproducible contractions. Intracellular [Ca2+] increased during activation; the increase in [Ca2+] preceded force development by approximately 2 s. After cessation of stimulation Ca2+ fell, preceding the fall in force by approximately 4 s. The fluorescence properties of fura-2 were determined with time-resolved spectroscopy using synchrotron light at the MAX-storage ring, Lund, Sweden. The fluorescence decay of free fura-2 was best described by two exponential decays (time constants approximately 0.5 and 1.5 ns) at low Ca2+ (pCa 9). At high Ca2+ (pCa 4.5), fluorescence decay became slower and could be fitted by one exponential decay (1.9 ns). Time-resolved anisotropy of free fura-2 was characteristic of free rotational motion (correlation time 0.3 ns). Motion of fura-2 could be markedly inhibited by high concentrations of creatine kinase. Time-resolved spectroscopy measurements of muscle fibers loaded with fura-2 showed that the fluorescence lifetime of the probe was longer, suggesting an influence of the chemical environment. Anisotropy measurements revealed, however, that the probe was mobile in the cells. The Ca2+-dependence of contraction and relaxation was studied using a photolabile calcium chelator, diazo-2, which could be loaded into the muscle cells in a similar manner as fura-2. Photolysis of diazo-2 leads to an increase in its Ca2+-affinity and a fall in free Ca2+. When muscles that had been loaded with diazo-2 were illuminated with UV light flashes during the rising phase of contraction, the rate of contraction became slower, suggesting a close relation between intracellular Ca2+ and the cross-bridge interaction. In contrast, photolysis during relaxation did not influence the rate of force decay, suggesting that relaxation of these contractions is not determined by the rate of Ca2+ removal or due to an increased Ca2+ sensitivity, but instead is limited by other processes such as deactivation by dephosphorylation or detachment of tension-bearing cross-bridges, possibly regulated by thin filament systems.
在22摄氏度下,采用fura-2技术测定兔直肠尾骨肌电诱导收缩过程中的细胞内Ca2+。对肌肉进行电刺激,使其产生短暂、可重复的收缩。激活过程中细胞内[Ca2+]升高;[Ca2+]的升高比力量产生提前约2秒。刺激停止后,Ca2+下降,比力量下降提前约4秒。使用瑞典隆德MAX储存环的同步加速器光,通过时间分辨光谱法测定fura-2的荧光特性。在低Ca2+(pCa 9)时,游离fura-2的荧光衰减最好用两个指数衰减(时间常数约为0.5和1.5纳秒)来描述。在高Ca2+(pCa 4.5)时,荧光衰减变慢,可用一个指数衰减(1.9纳秒)来拟合。游离fura-2的时间分辨各向异性具有自由旋转运动的特征(相关时间0.3纳秒)。高浓度的肌酸激酶可显著抑制fura-2的运动。对加载fura-2的肌纤维进行时间分辨光谱测量表明,探针的荧光寿命更长,这表明化学环境有影响。然而,各向异性测量显示,探针在细胞内是可移动的。使用光不稳定钙螯合剂重氮-2研究收缩和舒张的Ca2+依赖性,重氮-2可以与fura-2以类似的方式加载到肌肉细胞中。重氮-2的光解导致其Ca2+亲和力增加和游离Ca2+下降。当在收缩上升阶段用紫外线闪光照射加载了重氮-2的肌肉时,收缩速率变慢,这表明细胞内Ca2+与横桥相互作用之间存在密切关系。相反,舒张过程中的光解不影响力量衰减速率,这表明这些收缩的舒张不是由Ca2+去除速率决定的,也不是由于Ca2+敏感性增加,而是受其他过程限制,如去磷酸化失活或承受张力的横桥分离,可能由细肌丝系统调节。