Backx P H, Gao W D, Azan-Backx M D, Marban E
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
J Gen Physiol. 1995 Jan;105(1):1-19. doi: 10.1085/jgp.105.1.1.
The control of force by [Ca2+] was investigated in rat cardiac trabeculae loaded with fura-2 salt. At sarcomere lengths of 2.1-2.3 microns, the steady state force-[Ca2+]i relationship during tetanization in the presence of ryanodine was half maximally activated at a [Ca2+]i of 0.65 +/- 0.19 microM with a Hill coefficient of 5.2 +/- 1.2 (mean +/- SD, n = 9), and the maximal stress produced at saturating [Ca2+]i equalled 121 +/- 35 mN/mm2 (n = 9). The dependence of steady state force on [Ca2+]i was identical in muscles tetanized in the presence of the Ca(2+)-ATPase inhibitor cyclopiazonic acid (CPA). The force-[Ca2+]i relationship during the relaxation of twitches in the presence of CPA coincided exactly to that measured at steady state during tetani, suggesting that CPA slows the decay rate of [Ca2+]i sufficiently to allow the force to come into a steady state with the [Ca2+]i. In contrast, the relationship of force to [Ca2+]i during the relaxation phase of control twitches was shifted leftward relative to the steady state relationship, establishing that relaxation is limited by the contractile system itself, not by Ca2+ removal from the cytosol. Under control conditions the force-[Ca2+]i relationship, quantified at the time of peak twitch force (i.e., dF/dt = 0), coincided fairly well with steady state measurements in some trabeculae (i.e., three of seven). However, the force-[Ca2+]i relationship at peak force did not correspond to the steady state measurements after the application of 5 mM 2,3-butanedione monoxime (BDM) (to accelerate cross-bridge kinetics) or 100 microM CPA (to slow the relaxation of the [Ca2+]i transient). Therefore, we conclude that the relationship of force to [Ca2+]i during physiological twitch contractions cannot be used to predict the steady state relationship.
在加载了fura-2盐的大鼠心脏小梁中研究了[Ca2+]对力的控制。在肌节长度为2.1 - 2.3微米时，在存在ryanodine的情况下进行强直收缩时，稳态力与[Ca2+]i的关系在[Ca2+]i为0.65±0.19微摩尔时达到最大激活的一半，希尔系数为5.2±1.2（平均值±标准差，n = 9），并且在饱和[Ca2+]i时产生的最大应力等于121±35毫牛顿/平方毫米（n = 9）。在存在Ca(2+)-ATP酶抑制剂环匹阿尼酸（CPA）的情况下进行强直收缩的肌肉中，稳态力对[Ca2+]i的依赖性是相同的。在存在CPA的情况下，单收缩舒张过程中的力与[Ca2+]i关系与强直收缩时稳态测量值完全一致，这表明CPA充分减慢了[Ca2+]i的衰减速率，以使力与[Ca2+]i达到稳态。相比之下，对照单收缩舒张期的力与[Ca2+]i关系相对于稳态关系向左移动，这表明舒张受收缩系统本身限制，而非受细胞质中Ca2+清除的限制。在对照条件下，在单收缩峰值力时（即dF/dt = 0）量化的力与[Ca2+]i关系在一些小梁中（即七个中的三个）与稳态测量值相当吻合。然而，在应用5毫摩尔2,3 - 丁二酮单肟（BDM）（以加速横桥动力学）或100微摩尔CPA（以减慢[Ca2+]i瞬变的舒张）后，峰值力时的力与[Ca2+]i关系与稳态测量值不对应。因此，我们得出结论，生理单收缩收缩过程中力与[Ca2+]i的关系不能用于预测稳态关系。
