Abstract:
Calcium diffusion in the thin 100 nm layer located between the plasma membrane and docked vesicles in the pre-synaptic terminal of neuronal cells mediates vesicular fusion and synaptic transmission. Accounting for the narrow-cusp geometry located underneath the vesicle is a key ingredient that defines the probability and the time scale of calcium diffusion to bind calcium sensors for the initiation of vesicular release. We review here the time scale, the calcium binding dynamics and the consequences for asynchronous versus synchronous release. To conclude, three-dimensional modeling approaches and the associated coarse-grained simulations can now account efficiently for the precise co-organization of vesicles and Voltage-Gated-Calcium-Channel (VGCC). This co-organization is a key determinant of short-term plasticity and it shapes asynchronous release. Moreover, changing the location of VGCC from few nanometers underneath the vesicle modifies significantly the release probability. Finally, by modifying the calcium buffer concentration, a single synapse can switch from facilitation to depression.
摘要:
位于质膜和神经元细胞突触前末端对接囊泡之间的100nm薄层中的钙扩散介导囊泡融合和突触传递。考虑到位于囊泡下方的窄尖几何形状是定义钙扩散的概率和时间尺度以结合钙传感器以引发囊泡释放的关键因素。我们在这里回顾一下时间尺度,钙结合动力学以及异步释放与同步释放的后果。最后,三维建模方法和相关的粗粒度模拟现在可以有效地解释囊泡和电压门控钙通道(VGCC)的精确共组织。这种共同组织是短期可塑性的关键决定因素,它形成了异步释放。此外,从囊泡下方几纳米改变VGCC的位置显着改变释放概率。最后,通过改变钙缓冲液的浓度,单个突触可以从促进转变为抑郁。