Garetto L P, Carlsen R C, Lee J H, Walsh D A
Department of Biological Chemistry, School of Medicine, University of California, Davis 95616.
Mol Pharmacol. 1988 Feb;33(2):212-7.
Calcium-mediated phosphorylase kinase activation has been studied in the rat flexor digitorum brevis, a fast-twitch oxidative-glycolytic skeletal muscle that exhibits a robust inward Ca2+ current [Can J. Physiol. Pharmacol. 63:958-965, 1985]. This system provided an opportunity to compare the regulation of contraction and activation of phosphorylase by extracellular and intracellular sources of Ca2+. In muscles repetitively stimulated at 21 degrees, there appeared to be a close correlation between the control of contraction and phosphorylase activation. Blocking extracellular Ca2+ entry promoted an inactivation of phosphorylase and diminished the elevation of resting tension, which in untreated muscles ensues with the onset of fatigue. The response of muscles stimulated at 37 degrees was in distinct contrast. Phosphorylase, following initial rapid activation, was then briskly inactivated despite the continuation of a near-maximal contractile response. An elevation in resting tension during stimulation was observed at 37 degrees but was a transitory response in comparison to what was seen at 21 degrees. Blocking the entry of external Ca2+ inhibited this response. Sarcolemmal Ca2+ channel blockers had no effect on the observed phosphorylase response at 37 degrees, but phosphorylase was already nearly fully inactivated before their effects were manifested on contraction. Thus, at this temperature there is a clear dissociation between Ca2+-mediated regulation of contraction and the production of metabolic energy by enhanced glycogenolysis. This appears to occur because, although Ca2+ induces phosphorylase activation, a subsequent, but rapid non-Ca2+-mediated event promotes inactivation, even while Ca2+-mediated contraction is being sustained.
钙介导的磷酸化酶激酶激活已在大鼠趾短屈肌中进行了研究，该肌肉是一种快肌氧化 - 糖酵解型骨骼肌，表现出强大的内向Ca2 +电流[《加拿大生理学与药理学杂志》63:958 - 965，1985年]。该系统提供了一个机会来比较细胞外和细胞内Ca2 +来源对收缩的调节以及磷酸化酶的激活。在21摄氏度下重复刺激的肌肉中，收缩控制与磷酸化酶激活之间似乎存在密切相关性。阻断细胞外Ca2 +进入会促进磷酸化酶失活，并降低静息张力的升高，而在未处理的肌肉中，随着疲劳的开始会出现这种情况。在37摄氏度下刺激的肌肉的反应则明显不同。磷酸化酶在最初快速激活后，尽管持续接近最大收缩反应，但随后迅速失活。在37摄氏度下刺激期间观察到静息张力升高，但与在21摄氏度下看到的情况相比是一种短暂反应。阻断外部Ca2 +的进入会抑制这种反应。肌膜Ca2 +通道阻滞剂对在37摄氏度下观察到的磷酸化酶反应没有影响，但在其对收缩产生影响之前，磷酸化酶已经几乎完全失活。因此，在这个温度下，Ca2 +介导的收缩调节与通过增强糖原分解产生代谢能量之间存在明显的分离。这似乎是因为，尽管Ca2 +诱导磷酸化酶激活，但随后一个快速的非Ca2 +介导的事件会促进失活，即使Ca2 +介导的收缩仍在持续。
