Catacuzzeno Luigi, Fioretti Bernard, Franciolini Fabio
Dipartimento di Biologia Cellulare e Ambientale, Università di Perugia, Perugia, Italy.
Biophys J. 2008 Sep;95(5):2160-71. doi: 10.1529/biophysj.107.124909. Epub 2008 May 23.
Synchronous neurotransmitter release is mediated by the opening of voltage-gated Ca(2+) channels and the build-up of submembrane Ca(2+) microdomains. Previous models of Ca(2+) microdomains have neglected possible electrostatic interactions between Ca(2+) ions and negative surface charges on the inner leaflet of the plasma membrane. To address the effects of these interactions, we built a computational model of ion electrodiffusion described by the Nernst-Planck and Poisson equations. We found that inclusion of a negative surface charge significantly alters the spatial characteristics of Ca(2+) microdomains. Specifically, close to the membrane, Ca(2+) ions accumulate, as expected from the strong electrostatic attraction exerted on positively charged Ca(2+) ions. Farther away from the membrane, increasing the surface charge density results in a reduction of the Ca(2+) concentration because of the preferential spread of Ca(2+) ions along lateral directions. The model also predicts that the negative surface charge will decrease the spatial gradient of the Ca(2+) microdomain in the lateral direction, resulting in increased overlap of microdomains originating from different Ca(2+) channels. Finally, we found that surface charge increases the probability of vesicle release if the Ca(2+) sensor is located within the electrical double layer, whereas this probability is decreased if the Ca(2+) sensor lies at greater distances from the membrane. Our data suggest that membrane surface charges exert a significant influence on the profile of Ca(2+) microdomains, and should be taken into account in models of neurotransmitter release.
同步神经递质释放由电压门控Ca(2+)通道的开放和膜下Ca(2+)微区的形成介导。先前的Ca(2+)微区模型忽略了Ca(2+)离子与质膜内小叶上的负表面电荷之间可能存在的静电相互作用。为了研究这些相互作用的影响，我们构建了一个由能斯特-普朗克方程和泊松方程描述的离子电扩散计算模型。我们发现，包含负表面电荷会显著改变Ca(2+)微区的空间特征。具体而言，靠近膜处，Ca(2+)离子积累，这正如对带正电的Ca(2+)离子施加的强静电吸引所预期的那样。离膜更远时，由于Ca(2+)离子沿横向优先扩散，增加表面电荷密度会导致Ca(2+)浓度降低。该模型还预测，负表面电荷将减小Ca(2+)微区在横向的空间梯度，导致源自不同Ca(2+)通道的微区重叠增加。最后，我们发现，如果Ca(2+)传感器位于双电层内，表面电荷会增加囊泡释放的概率，而如果Ca(2+)传感器距离膜更远，则该概率会降低。我们的数据表明，膜表面电荷对Ca(2+)微区的分布有显著影响，在神经递质释放模型中应予以考虑。
