COMPUTER-SIMULATIONS OF N-METHYL-D-ASPARTATE RECEPTOR-INDUCED MEMBRANE-PROPERTIES IN A NEURON MODEL
COMPUTER-SIMULATIONS OF N-METHYL-D-ASPARTATE RECEPTOR-INDUCED MEMBRANE-PROPERTIES IN A NEURON MODEL
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DOI：
10.1152/jn.1991.66.2.473
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发表时间：
1991-08-01
影响因子：
2.5
通讯作者：
GRILLNER, S
中科院分区：
文献类型：
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作者：
BRODIN, L;TRAVEN, HGC;GRILLNER, S
1.为了评估N-甲基-D-天冬氨酸(NMDA)受体在模拟七鳃鳗脊髓运动网络中的作用，我们建立了一个计算机模拟的神经元电模型，除了电压门控的Na+，K+和Ca~(2+)通道和Ca~(2+)激活的K~+通道[K(Ca)通道]外，还包含NMDA通道。采用开放通道模型模拟了流经NMDA通道的Na+-K+电流中镁离子阻滞剂的电压依赖性。为了解释NMDA和膜电压对K(Ca)通道的调节，我们模拟了两个不同的钙离子池，它们具有不同的电压依赖性和动态。在模型神经元中可以诱发起搏样膜电位振荡，这类似于在沐浴NMDA和河豚毒素存在时实验观察到的。测试了改变不同通道参数的效果，以确定在什么条件下可以发生这种膜电位振荡。振荡幅度由激活NMDA通道和电压依赖性K+通道的电位水平决定。去极化(NMDA通道)和超极化[K(Ca)通道]电流之间的平衡决定了振荡的频率和去极化和超极化振荡的相对持续时间。模拟的镁离子浓度和K+电导的变化以及恒流的注入引起了与实验观测相对应的振荡的变化。可以通过短暂的电流脉冲来重置去极化和超极化阶段。我们的结论是，本模型可以解释沐浴NMDA对脊髓神经元的影响。这使得将NMDA受体介导的特性纳入七鳃鳗运动网络的模拟模型中。
1. To evaluate the role of N-methyl-D-aspartate (NMDA) receptors in simulations of the lamprey spinal locomotor network, we developed a computer-simulated electrical model of a neuron that contains NMDA channels in addition to voltage-gated Na+, K+, and Ca2+ Channels and Ca2+-activated K+ channels [K(Ca) channels].2. The voltage dependence of the Mg2+ block of the Na+-K+ current flow through the NMDA channel was modeled according to a scheme of open-channel block. To account for the regulation of K(Ca) channels by NMDA and membrane voltage, we modeled two separate Ca2+ pools that had different voltage dependencies and dynamics.3. Pacemaker-like membrane potential oscillations could be elicited in the model neuron, which resembled those observed experimentally in the presence of bath-applied NMDA and tetrodotoxin. The effect of changing different channel parameters were tested to determine under which conditions such membrane potential oscillations could occur.4. The oscillation amplitude was determined by the potential levels at which the NMDA channels and voltage-dependent K+ channels, respectively, were activated. The oscillation frequency and the relative durations of the de- and hyperpolarized phases of the oscillations were determined by the balance between the depolarizing (NMDA channels) and hyperpolarizing [K(Ca) channels] currents.5. Simulated alterations of the Mg2+ concentration and the K+ conductance as well as injection of constant current caused changes of the oscillations corresponding to those observed experimentally. The de- and hyperpolarizing phases could be reset by brief current pulses.6. We conclude that the present model can account for the effects of bath-applied NMDA on spinal neurons. This permits an incorporation of NMDA-receptor-mediated properties in simulation models of the lamprey locomotor network.