Dettbarn C, Györke S, Palade P
Department of Physiology and Biophysics, University of Texas Medical Branch, Galveston 77555-0641.
Mol Pharmacol. 1994 Sep;46(3):502-7.
Ryanodine receptors have recently been shown to undergo an unusual kind of inactivation process termed adaptation, which bears similarities to the transient calcium releases induced in other systems by successive incremental additions of inositol-1,4,5-trisphosphate. Such releases are sometimes termed "quantal". In this study we report that many agonists induce similar behavior in muscle sarcoplasmic reticulum and that the responses depend not on the calcium pumps therein but rather on the ryanodine receptors. The chemical diversity of these agonists makes it very unlikely that adaptation simply affects the sensitivity of the receptor to agonists at any one binding site. More likely, this result indicates that adaptive behavior of ryanodine receptors results whenever the ryanodine receptor is activated and that this process affects the action of most, if not all, agonists. Evidence is presented suggesting that the releases observed do not represent all-or-none releases from vesicle subpopulations (true quantal behavior) but rather seem to involve partial release from more homogeneously sensitive stores, a process referred to here as adaptation or increment detection.
最近研究表明,兰尼碱受体(Ryanodine receptors)会经历一种不同寻常的失活过程,即适应性变化,这种变化类似于在其他系统中由连续递增添加肌醇-1,4,5-三磷酸(inositol-1,4,5-trisphosphate)所诱导的瞬时钙释放。这种释放有时被称为“量子化”。在本研究中,我们报告了许多激动剂在肌肉肌浆网中会引发类似的行为,并且这些反应并非取决于其中的钙泵,而是取决于兰尼碱受体。这些激动剂的化学多样性使得适应性变化仅仅影响受体在任何一个结合位点对激动剂的敏感性这一可能性变得微乎其微。更有可能的是,这一结果表明,只要兰尼碱受体被激活,就会出现兰尼碱受体的适应性行为,并且这一过程会影响大多数(如果不是全部)激动剂的作用。有证据表明,所观察到的释放并非代表来自囊泡亚群的全或无释放(真正的量子化行为),而是似乎涉及从更均匀敏感的储存库中进行部分释放,在此过程中被称为适应性变化或增量检测。