Uteshev V V, Pennefather P S
Faculty of Pharmacy, University of Toronto, Ontario, Canada.
Biophys J. 1997 Mar;72(3):1127-34. doi: 10.1016/S0006-3495(97)78761-7.
Chemical synaptic transmission is a fundamental component of interneuronal communications in the central nervous system (CNS). Discharge of a presynaptic vesicle containing a few thousand molecules (a quantum) of neurotransmitter into the synaptic cleft generates a transmitter concentration signal that drives postsynaptic ion-channel receptors. These receptors exhibit multiple states, with state transition kinetics dependent on neurotransmitter concentration. Here, a novel and simple analytical approach for describing gating of multi-state receptors by signals with complex continuous time courses is used to describe the generation of glutamate-mediated quantal postsynaptic responses at brain synapses. The neurotransmitter signal, experienced by multi-state N-methyl-D-aspartate (NMDA)- and L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-type glutamate receptors at specific points in a synaptic cleft, is approximated by a series of step functions of different intensity and duration and used to drive a Markovian, multi-state kinetic scheme that describes receptor gating. Occupancy vectors at any point in time can be computed interatively from the occupancy vectors at the times of steps in transmitter concentration. Multi-state kinetic schemes for both the low-affinity AMPA subtype of glutamate receptor and for the high-affinity NMDA subtype are considered, and expected NMDA and AMPA components of synaptic currents are calculated. The amplitude of quantal responses mediated by postsynaptic receptor clusters having specific spatial distributions relative to foci of quantal neurotransmitter release is then calculated and related to the displacement between the center of the postsynaptic receptor cluster and the focus of synaptic vesicle discharge. Using this approach we show that the spatial relation between the focus of release and the center of the postsynaptic receptor cluster affects synaptic efficacy. We also show how variation in this relation contributes to variation in synaptic current amplitudes.
化学突触传递是中枢神经系统（CNS）中神经元间通讯的基本组成部分。含有数千个神经递质分子（一个量子）的突触前囊泡释放到突触间隙中，产生一个驱动突触后离子通道受体的递质浓度信号。这些受体呈现多种状态，状态转换动力学取决于神经递质浓度。在这里，一种新颖且简单的分析方法被用于描述具有复杂连续时间进程的信号对多状态受体的门控，该方法用于描述脑突触处谷氨酸介导的量子突触后反应的产生。在突触间隙特定点处，多状态N - 甲基 - D - 天冬氨酸（NMDA）型和L - α - 氨基 - 3 - 羟基 - 5 - 甲基 - 4 - 异恶唑丙酸（AMPA）型谷氨酸受体所经历的神经递质信号，由一系列不同强度和持续时间的阶跃函数近似，并用于驱动描述受体门控的马尔可夫多状态动力学方案。任何时刻的占据向量都可以根据递质浓度阶跃时刻的占据向量迭代计算得出。考虑了谷氨酸受体低亲和力AMPA亚型和高亲和力NMDA亚型的多状态动力学方案，并计算了突触电流的预期NMDA和AMPA成分。然后计算由相对于量子神经递质释放焦点具有特定空间分布的突触后受体簇介导的量子反应的幅度，并将其与突触后受体簇中心和突触小泡释放焦点之间的位移相关联。使用这种方法，我们表明释放焦点与突触后受体簇中心之间的空间关系会影响突触效能。我们还展示了这种关系的变化如何导致突触电流幅度的变化。
