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):2201-21. doi: 10.1016/S0006-3495(00)76769-5.
A Monte Carlo analysis has been made of calcium dynamics and quantal secretion at microdomains in which the calcium reaches very high concentrations over distances of <50 nm from a channel and for which calcium dynamics are dominated by diffusion. The kinetics of calcium ions in microdomains due to either the spontaneous or evoked opening of a calcium channel, both of which are stochastic events, are described in the presence of endogenous fixed and mobile buffers. Fluctuations in the number of calcium ions within 50 nm of a channel are considerable, with the standard deviation about half the mean. Within 10 nm of a channel these numbers of ions can give rise to calcium concentrations of the order of 100 microM. The temporal changes in free calcium and calcium bound to different affinity indicators in the volume of an entire varicosity or bouton following the opening of a single channel are also determined. A Monte Carlo analysis is also presented of how the dynamics of calcium ions at active zones, after the arrival of an action potential and the stochastic opening of a calcium channel, determine the probability of exocytosis from docked vesicles near the channel. The synaptic vesicles in active zones are found docked in a complex with their calcium-sensor associated proteins and a voltage-sensitive calcium channel, forming a secretory unit. The probability of quantal secretion from an isolated secretory unit has been determined for different distances of an open calcium channel from the calcium sensor within an individual unit: a threefold decrease in the probability of secretion of a quantum occurs with a doubling of the distance from 25 to 50 nm. The Monte Carlo analysis also shows that the probability of secretion of a quantum is most sensitive to the size of the single-channel current compared with its sensitivity to either the binding rates of the sites on the calcium-sensor protein or to the number of these sites that must bind a calcium ion to trigger exocytosis of a vesicle.
对微区内的钙动力学和量子分泌进行了蒙特卡罗分析,在这些微区内,钙在距通道小于50 nm的距离上达到非常高的浓度,且钙动力学以扩散为主导。在存在内源性固定和移动缓冲剂的情况下,描述了由于钙通道的自发或诱发开放(两者均为随机事件)而导致的微区内钙离子的动力学。通道50 nm范围内钙离子数量的波动相当大,标准差约为平均值的一半。在通道10 nm范围内,这些离子数量可产生约100 microM的钙浓度。还确定了单个通道开放后,整个曲张体或终扣体积中游离钙和与不同亲和力指示剂结合的钙的时间变化。还进行了蒙特卡罗分析,以研究动作电位到达和钙通道随机开放后,活跃区钙离子的动力学如何决定通道附近停靠囊泡的胞吐概率。发现活跃区的突触囊泡与它们的钙传感器相关蛋白和电压敏感钙通道形成复合物停靠,形成一个分泌单位。已确定了单个单位内开放钙通道与钙传感器之间不同距离时,孤立分泌单位量子分泌的概率:距离从25 nm加倍到50 nm时,量子分泌概率降低三倍。蒙特卡罗分析还表明,与量子分泌概率对钙传感器蛋白上位点的结合速率或触发囊泡胞吐所需结合钙离子的这些位点数量的敏感性相比,它对单通道电流大小最为敏感。