Jackson Meyer B
Department of Neuroscience, University of Wisconsin-Madison, Madison, Wisconsin.
Biophys J. 2024 Sep 17;123(18):2969-2973. doi: 10.1016/j.bpj.2024.07.038. Epub 2024 Jul 31.
Despite the importance of speed in synaptic transmission, in many synapses, neurotransmitters bind to their receptors at rates that appear to be slower than the diffusion limit. This assessment is generally based on a comparison with the Smoluchowski limit rather than an independent experimental analysis. In many synapses, miniature excitatory postsynaptic currents (mEPSCs) are controlled by the interplay between binding to receptors and diffusion of the neurotransmitter out of the synaptic cleft. A model for mEPSCs that incorporates these features was used to evaluate published data showing that elevated viscosity increases mEPSC amplitude. With diffusion-limited binding, the model predicts that raising the viscosity will decrease the amplitude rather than increase it. Diffusion-independent binding predicts an increase that is larger than that observed. To explore the intermediate behavior between the diffusion-limited and diffusion-independent extremes, a general expression for intermolecular rates was used that depends on both collision frequency and intrinsic reactivity. This analysis yielded an estimate for collision frequency that is about an order of magnitude above the measured rate of association and an order of magnitude below the Smoluchowski limit.
尽管速度在突触传递中很重要，但在许多突触中，神经递质与其受体结合的速率似乎比扩散极限要慢。这种评估通常基于与斯莫卢霍夫斯基极限的比较，而非独立的实验分析。在许多突触中，微小兴奋性突触后电流（mEPSCs）受神经递质与受体结合以及从突触间隙扩散之间相互作用的控制。一个纳入这些特征的mEPSCs模型被用于评估已发表的数据，这些数据表明粘度升高会增加mEPSC幅度。对于扩散受限的结合，该模型预测提高粘度会降低而非增加幅度。与扩散无关的结合预测的增加幅度比观察到的要大。为了探究扩散受限和与扩散无关这两个极端之间的中间行为，使用了一个依赖于碰撞频率和固有反应性的分子间速率通用表达式。该分析得出的碰撞频率估计值比测得的缔合速率高约一个数量级，比斯莫卢霍夫斯基极限低一个数量级。
