Blank P S, Vogel S S, Cho M S, Kaplan D, Bhuva D, Malley J, Zimmerberg J
Laboratory of Cellular and Molecular Biophysics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Gen Physiol. 1998 Nov;112(5):569-76. doi: 10.1085/jgp.112.5.569.
Differences in the calcium sensitivity of individual secretory vesicles can explain a defining feature of calcium-regulated exocytosis, a graded response to calcium. The role of the time dependence of calcium delivery in defining the observed differences in the calcium sensitivity of sea urchin egg secretory vesicles in vitro was examined. The calcium sensitivity of individual secretory vesicles (i.e., the distribution of calcium thresholds) is invariant over a range of calcium delivery rates from faster than micromolar per millisecond to slower than micromolar per second. Any specific calcium concentration above threshold triggers subpopulations of vesicles to fuse, and the size of these subpopulations is independent of the time course required to reach that calcium concentration. All evidence supports the hypothesis that the magnitude of the free calcium is the single controlling variable that determines the fraction of vesicles that fuse, and that this fraction is established before the application of calcium. Submaximal responses to calcium cannot be attributed to alterations in the calcium sensitivity of individual secretory vesicles arising from the temporal properties of the calcium delivery. Models that attempt to explain the cessation of fusion using changes in the distribution of calcium thresholds arising from the rate of calcium delivery and/or adaptation are not applicable to this system, and thus cannot be general.
单个分泌囊泡钙敏感性的差异可以解释钙调节胞吐作用的一个决定性特征,即对钙的分级反应。研究了钙传递的时间依赖性在体外定义海胆卵分泌囊泡钙敏感性观察差异中的作用。在从快于微摩尔每秒到慢于微摩尔每秒的一系列钙传递速率范围内,单个分泌囊泡的钙敏感性(即钙阈值的分布)是不变的。任何高于阈值的特定钙浓度都会触发囊泡亚群融合,并且这些亚群的大小与达到该钙浓度所需的时间进程无关。所有证据都支持这样的假设,即游离钙的量是决定融合囊泡比例的单一控制变量,并且这个比例在施加钙之前就已确定。对钙的次最大反应不能归因于由钙传递的时间特性引起的单个分泌囊泡钙敏感性的改变。试图用由钙传递速率和/或适应性引起的钙阈值分布变化来解释融合停止的模型不适用于这个系统,因此不能一概而论。