Même W, Huchet-Cadiou C, Léoty C
Laboratoire de Physiologie Générale, Centre National de la Recherche Scientifique, ERS 6107, Faculté des Sciences et des Techniques, Nantes, France.
Am J Physiol. 1998 Jan;274(1):C253-61. doi: 10.1152/ajpcell.1998.274.1.C253.
The effects of cyclopiazonic acid (CPA) were investigated on isolated skeletal muscle fibers of frog semitendinosus muscle. CPA (0.5-10 microM) enhanced isometric twitch but produced little change in resting tension. At higher concentrations (10-50 microM), CPA depressed twitch and induced sustained contracture without affecting resting and action potentials. In Triton-skinned fibers, CPA had no significant effect on myofibrillar Ca2+ sensitivity but decreased maximal activated force at concentrations > 5 microM. In intact cells loaded with the Ca2+ fluorescence indicator indo 1, CPA (2 microM) induced an increase in Ca(2+)-transient amplitude (10 +/- 2.5%), which was associated with an increase in time to peak and in the time constant of decay. Consequently, peak force was increased by 35 +/- 4%, and both time to peak and the time constant of relaxation were prolonged. It is concluded that CPA effects, at a concentration of up to 2 microM, were associated with specific inhibition of sarcoplasmic reticulum Ca(2+)-adenosinetriphosphatase in intact skeletal muscle and that inhibition of the pump directly affected the handling of intracellular Ca2+ and force production.
研究了环匹阿尼酸（CPA）对青蛙半腱肌分离骨骼肌纤维的影响。CPA（0.5 - 10微摩尔）增强了等长收缩，但对静息张力影响不大。在较高浓度（10 - 50微摩尔）时，CPA抑制收缩并诱导持续挛缩，而不影响静息电位和动作电位。在经曲拉通处理的肌纤维中，CPA对肌原纤维Ca2 +敏感性无显著影响，但在浓度> 5微摩尔时降低了最大激活力。在加载了Ca2 +荧光指示剂indo 1的完整细胞中，CPA（2微摩尔）诱导Ca(2 +) - 瞬变幅度增加（10±2.5%），这与达到峰值的时间增加以及衰减时间常数增加有关。因此，峰值力增加了35±4%，达到峰值的时间和松弛时间常数均延长。结论是，在浓度高达2微摩尔时，CPA的作用与完整骨骼肌中肌浆网Ca(2 +) - 腺苷三磷酸酶的特异性抑制有关，并且泵的抑制直接影响细胞内Ca2 +的处理和力的产生。
