PRESYNAPTIC CALCIUM DIFFUSION FROM VARIOUS ARRAYS OF SINGLE CHANNELS - IMPLICATIONS FOR TRANSMITTER RELEASE AND SYNAPTIC FACILITATION
PRESYNAPTIC CALCIUM DIFFUSION FROM VARIOUS ARRAYS OF SINGLE CHANNELS - IMPLICATIONS FOR TRANSMITTER RELEASE AND SYNAPTIC FACILITATION
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DOI：
10.1016/s0006-3495(85)83863-7
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发表时间：
1985-12-01
影响因子：
3.4
通讯作者：
ZUCKER, RS
中科院分区：
文献类型：
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作者：
FOGELSON, AL;ZUCKER, RS
突触前钙向膜外扩散的一维模型，包括细胞质结合、表面泵的挤压和动作电位期间的内流，可以解释相递质释放的快速衰减和突触易化在一个峰值后的缓慢衰减，以及实验观察到的游离钙总量的缓慢下降。然而，使用该模型的模拟，以及包括钙摄取到细胞器和饱和结合在内的替代版本，未能保持长破伤风中递质释放到峰值的相位。建立了一个三维扩散模型，其中钙通过离散的膜通道进入，并在进入点50nm内释放递质。该模型的方程解析解基于超微结构观察，其中钙通道分布在活动带斑块中，成功地预测了突触易化，向破伤风峰的相释放以及总游离钙的积累。探讨了不同钙缓冲、泵送速率、通道数量和分布的影响。模拟了适合鱿鱼巨突触和青蛙神经肌肉连接的版本。讨论了关键假设的局限性，特别是快速不饱和结合。
A one-dimensional model of presynaptic calcium diffusion away from the membrane, with cytoplasmic binding, extrusion by a surface pump, and influx during action potentials, can account for the rapid decay of phasic transmitter release and the slower decay of synaptic facilitation following one spike, as well as the very slow decline in total free calcium observed experimentally. However, simulations using this model, and alternative versions in which calcium uptake into organelles and saturable binding are included, fail to preserve phasic transmitter release to spikes in a long tetanus. A three-dimensional diffusion model was developed, in which calcium enters through discrete membrane channels and acts to release transmitter within 50 nm of entry points. Analytic solutions of the equations of this model, in which calcium channels were distributed in active zone patches based on ultrastructural observations, were successful in predicting synaptic facilitation, phasic release to tetanic spikes, and the accumulation of total free calcium. The effects of varying calcium buffering, pump rate, and channel number and distribution were explored. Versions appropriate to squid giant synapses and frog neuromuscular junctions were simulated. Limitations of key assumptions, particularly rapid nonsaturable binding, are discussed.