Tegnér J, Hellgren-Kotaleski J, Lansner A, Grillner S
Nobel Institute for Neurophysiology, Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
J Neurophysiol. 1997 Apr;77(4):1795-812. doi: 10.1152/jn.1997.77.4.1795.
To evaluate the role of low-voltage-activated (LVA) calcium channels in the lamprey spinal locomotor network, a previous computer simulation model has been extended to include LVA calcium channels. It is also of interest to explore the consequences of a LVA conductance for the electrical behavior of the single neuron. The LVA calcium channel was modeled with voltage-dependent activation and inactivation using the m3h form, following a Hodgkin-Huxley paradigm. Experimental data from lamprey neurons was used to provide parameter values of the single cell model. The presence of a LVA calcium conductance in the model could account for the occurrence of a rebound depolarization in the simulation model. The influence of holding potential on the occurrence of a rebound as well the latency at which it is elicited was investigated and compared with previous experiments. The probability of a rebound increased at a more depolarized holding potential and the latency was also reduced under these conditions. Furthermore, the effect of changing the holding potential and the reversal potential of the calcium dependent potassium conductance were tested to determine under which conditions several rebound spikes could be elicited after a single inhibitory pulse in the simulation model. A reduction of the slow afterhyperpolarization (sAHP) after the action potential reduced the tendency for a train of rebound spikes. The experimental effects of gamma-aminobutyric acid-B (GABA(B)) receptor activation were simulated by reducing the maximal LVA calcium conductance. A reduced tendency for rebound firing and a slower rising phase with sinusoidal current stimulation was observed, in accordance with earlier experiments. The effect of reducing the slow afterhyperpolarization and reducing the LVA calcium current was tested experimentally in the lamprey spinal cord, during N-methyl-D-aspartate (NMDA)-induced fictive locomotion. The reduction of burst frequency was more pronounced with GABA(B) agonists than with apamin (inhibitor of K(Ca) current) when using high NMDA concentration (high burst frequency). The burst frequency increased after the addition of a LVA calcium current to the simulated segmental network, due to a faster recovery during the inhibitory phase as the activity switches between the sides. This result is consistent with earlier experimental findings because GABA(B) receptor agonists reduce the locomotor frequency. These results taken together suggest that the LVA calcium channels contribute to a larger degree with respect to the burst frequency regulation than the sAHP mechanism at higher burst frequencies. The range in which a regular burst pattern can be simulated is extended in the lower range by the addition of LVA calcium channels, which leads to more stable activity at low locomotor frequencies. We conclude that the present model can account for rebound firing and trains of rebound spikes in lamprey neurons. The effects of GABA(B) receptor activation on the network level is consistent with a reduction of the calcium current through LVA calcium channels even though GABA(B) receptor activation will affect the sAHP indirectly and also presynaptic inhibition.
为了评估低电压激活（LVA）钙通道在七鳃鳗脊髓运动网络中的作用，之前的计算机模拟模型已进行扩展，纳入了LVA钙通道。探究LVA电导对单个神经元电行为的影响也很有意义。LVA钙通道采用霍奇金 - 赫胥黎范式，通过m3h形式进行电压依赖性激活和失活建模。七鳃鳗神经元的实验数据用于提供单细胞模型的参数值。模型中LVA钙电导的存在可以解释模拟模型中反弹去极化的发生。研究了钳制电位对反弹发生的影响以及引发反弹的潜伏期，并与之前的实验进行了比较。在更去极化的钳制电位下，反弹的概率增加，并且在这些条件下潜伏期也缩短。此外，测试了改变钳制电位和钙依赖性钾电导的反转电位的效果，以确定在模拟模型中单个抑制性脉冲后在何种条件下可以引发多个反弹尖峰。动作电位后的慢后超极化（sAHP）的降低减少了一系列反弹尖峰的趋势。通过降低最大LVA钙电导来模拟γ-氨基丁酸 - B（GABA(B)）受体激活的实验效果。观察到反弹放电的趋势降低，并且在正弦电流刺激下上升阶段更慢，这与早期实验一致。在七鳃鳗脊髓中，在N-甲基-D-天冬氨酸（NMDA）诱导的虚拟运动期间，实验测试了降低慢后超极化和降低LVA钙电流的效果。当使用高NMDA浓度（高爆发频率）时，GABA(B)激动剂比阿帕明（K(Ca)电流抑制剂）对爆发频率的降低更明显。在模拟的节段网络中添加LVA钙电流后，爆发频率增加，这是因为在抑制阶段两侧活动切换时恢复更快。该结果与早期实验结果一致，因为GABA(B)受体激动剂会降低运动频率。这些结果综合表明，在较高爆发频率下，LVA钙通道在调节爆发频率方面比sAHP机制贡献更大。通过添加LVA钙通道，在较低范围内可以扩展能够模拟规则爆发模式的范围，这导致在低运动频率下活动更稳定。我们得出结论，当前模型可以解释七鳃鳗神经元中的反弹放电和一系列反弹尖峰。GABA(B)受体激活在网络水平上的作用与通过LVA钙通道的钙电流减少一致，尽管GABA(B)受体激活将间接影响sAHP以及突触前抑制。
