Bennett M R, Farnell L, Gibson W G
The Neurobiology Laboratory, Institute for Biomedical Research, Department of Physiology, University of Sydney, New South Wales 2006, Australia.
Biophys J. 2000 May;78(5):2222-40. doi: 10.1016/S0006-3495(00)76770-1.
A Monte Carlo analysis has been made of calcium dynamics in submembranous domains of active zones in which the calcium contributed by the opening of many channels is pooled. The kinetics of calcium ions in these domains has been determined using simulations for channels arranged in different geometries, according to the active zone under consideration: rectangular grids for varicosities and boutons and lines for motor-nerve terminals. The effects of endogenous fixed and mobile buffers on the two-dimensional distribution of free calcium ions at these active zones are then given, together with the extent to which these are perturbed and can be detected with different affinity calcium indicators when the calcium channels open stochastically under an action potential. A Monte Carlo analysis of how the dynamics of calcium ions in the submembranous domains determines the probability of exocytosis from docked vesicles is also presented. The spatial distribution of exocytosis from rectangular arrays of secretory units is such that exocytosis is largely excluded from the edges of the array, due to the effects of endogenous buffers. There is a steeper than linear increase in quantal release with an increase in the number of secretory units in the array, indicating that there is not just a local interaction between secretory units. Conditioning action potentials promote an increase in quantal release by a subsequent action potential primarily by depleting the fixed and mobile buffers in the center of the array. In the case of two parallel lines of secretory units exocytosis is random, and diffusion, together with the endogenous calcium buffers, ensures that the secretory units only interact over relatively short distances. As a consequence of this and in contrast to the case of the rectangular array, there is a linear relationship between the extent of quantal secretion from these zones and their length, for lengths greater than a critical value. This Monte Carlo analysis successfully predicts the relationship between the size and geometry of active zones and the probability of quantal secretion at these, the existence of quantal versus multiquantal release at different active zones, and the origins of the F1 phase of facilitation in synapses possessing different active zone geometries.
已对活动区膜下区域的钙动力学进行了蒙特卡罗分析，在这些区域中，许多通道开放所贡献的钙会聚集在一起。根据所考虑的活动区，使用针对不同几何排列通道的模拟，确定了这些区域中钙离子的动力学：曲张体和终扣为矩形网格，运动神经末梢为线。然后给出了内源性固定和移动缓冲剂对这些活动区游离钙离子二维分布的影响，以及当钙通道在动作电位下随机开放时，这些分布受到干扰的程度以及用不同亲和力的钙指示剂检测到的程度。还给出了膜下区域钙离子动力学如何决定停靠囊泡胞吐概率的蒙特卡罗分析。分泌单位矩形阵列的胞吐空间分布使得由于内源性缓冲剂的作用，阵列边缘基本不发生胞吐。随着阵列中分泌单位数量的增加，量子释放呈超线性增加，这表明分泌单位之间不仅存在局部相互作用。条件动作电位主要通过耗尽阵列中心的固定和移动缓冲剂来促进后续动作电位引起的量子释放增加。在两条平行的分泌单位线的情况下，胞吐是随机的，扩散与内源性钙缓冲剂一起确保分泌单位仅在相对较短的距离内相互作用。因此，与矩形阵列的情况不同，对于长度大于临界值的情况，这些区域的量子分泌程度与其长度之间存在线性关系。这种蒙特卡罗分析成功预测了活动区的大小和几何形状与这些区域量子分泌概率之间的关系、不同活动区量子释放与多量子释放的存在情况，以及具有不同活动区几何形状的突触中易化F1相的起源。
