Modeling study of the effects of overlapping Ca2+ microdomains on neurotransmitter release
Modeling study of the effects of overlapping Ca2+ microdomains on neurotransmitter release
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DOI：
10.1016/s0006-3495(99)77240-1
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发表时间：
1999-02-01
影响因子：
3.4
通讯作者：
Sherman, A
中科院分区：
文献类型：
--
作者：
Bertram, R;Smith, GD;Sherman, A
虽然单通道Ca2+微区在某些情况下能够门控神经递质释放，但在许多情况下，来自几个开放通道的微区可能重叠以激活囊泡融合。我们描述了一个数学模型，在该模型中，发射器释放门控由附近的Ca2+通道的开放所产生的单个或重叠的Ca2+微域。该模型解释了移动的Ca2+缓冲液的存在，前提是缓冲液是不饱和的，或者它在具有相对于Ca2+扩散快速的Ca2+结合动力学的开放通道附近是饱和的。我们发现，释放时间过程是不受影响的通道的位置（至少对于距离高达50 nm），但配对脉冲促进是更大的通道时，更远离释放网站。然后，我们开发了将选择性或随机通道阻断后的部分释放与释放和突触前Ca 2+电流之间的合作关系联系起来的公式。这些公式与发射机释放模型来研究这种形式的协同性，我们称之为钙电流协同性，移动的缓冲区和局部几何形状的钙通道的依赖。我们发现，Ca2+电流的协同性增加的通道数量每个释放网站，但大大低于通道的数量，理论上限。在饱和的移动的缓冲液的存在下，Ca2+电流的协同性更大，并且它随着通道的数量而更迅速地增加。最后，Ca2+电流协同性是通道距离的递增函数，特别是在饱和移动的缓冲区的存在下。
Although single-channel Ca2+ microdomains are capable of gating neurotransmitter release in some instances, it is likely that in many cases the microdomains from several open channels overlap to activate Vesicle fusion. We describe a mathematical model in which transmitter release is gated by single or overlapping Ca2+ microdomains produced by the opening of nearby Ca2+ channels. This model accounts for the presence of a mobile Ca2+ buffer, provided either that the buffer is unsaturable or that it is saturated near an open channel with Ca2+ binding kinetics that are rapid relative to Ca2+ diffusion. We show that the release time course is unaffected by the location of the channels (at least for distances up to 50 nm), but paired-pulse facilitation is greater when the channels are farther from the release sites. We then develop formulas relating the fractional release following selective or random channel blockage to the cooperative relationship between release and the presynaptic Ca2+ current. These formulas are used with the transmitter release model to study the dependence of this form of cooperativity, which we call Ca2+ current cooperativity, on mobile buffers and on the local geometry of Ca2+ channels. We find that Ca2+ current cooperativity increases with the number of channels per release site, but is considerably less than the number of channels, the theoretical upper bound. In the presence of a saturating mobile buffer the Ca2+ current cooperativity is greater, and it increases more rapidly with the number of channels. Finally, Ca2+ current cooperativity is an increasing function of channel distance, particularly in the presence of saturating mobile buffer.