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多巴胺对瞬时钾电流的调节在中枢模式发生器网络中引起相位偏移。

Dopamine modulation of transient potassium current evokes phase shifts in a central pattern generator network.

作者信息

Harris-Warrick R M, Coniglio L M, Barazangi N, Guckenheimer J, Gueron S

机构信息

Section of Neurobiology and Behavior, Cornell University, Ithaca, New York 14853.

出版信息

J Neurosci. 1995 Jan;15(1 Pt 1):342-58. doi: 10.1523/JNEUROSCI.15-01-00342.1995.

DOI:10.1523/JNEUROSCI.15-01-00342.1995
PMID:7823140
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6578330/
Abstract

Bath application of dopamine modifies the rhythmic motor pattern generated by the 14 neuron pyloric network in the stomatogastric ganglion of the spiny lobster, Panulirus interruptus. Among other effects, dopamine excites many of the pyloric constrictor (PY) neurons to fire at high frequency and phase-advances the timing of their activity in the motor pattern. These responses arise in part from direct actions of dopamine to modulate the intrinsic electrophysiological properties of the PY cells, and can be studied in synaptically isolated neurons. The rate of rebound following a hyperpolarizing prestep and the spike frequency during a subsequent depolarization are both accelerated by dopamine. Based on theoretical simulations, Hartline (1979) suggested that the rate of postinhibitory rebound in stomatogastric neurons could vary with the amount of voltage-sensitive transient potassium current (IA). Consistent with this prediction, we found that dopamine evokes a net conductance decrease in synaptically isolated PY neurons. In voltage clamp, dopamine reduces IA, specifically by reducing the amplitude of the slowly inactivating component of the current and shifting its voltage activation curve in the depolarized direction. 4-Aminopyridine, a selective blocker of IA in stomatogastric neurons, mimics and occludes the effects of dopamine on isolated PY neurons. A conductance-based mathematical model of the PY neuron shows appropriate changes in activity upon quantitative modification of the IA parameters affected by dopamine. These results demonstrate that dopamine excites and phase-advances the PY neurons in the rhythmic pyloric motor pattern at least in part by reducing the transient K+ current, IA.

摘要

在多刺龙虾(Panulirus interruptus)的口胃神经节中,向浴槽中施加多巴胺会改变由14个神经元组成的幽门网络所产生的节律性运动模式。除其他作用外,多巴胺会使许多幽门收缩神经元(PY)高频放电,并使它们在运动模式中的活动时间提前。这些反应部分源于多巴胺对PY细胞内在电生理特性的直接作用,并且可以在突触隔离的神经元中进行研究。多巴胺会加速超极化预脉冲后的反弹速率以及随后去极化期间的放电频率。基于理论模拟,哈特林(1979年)提出,口胃神经元中抑制后反弹的速率可能会随电压敏感型瞬时钾电流(IA)的量而变化。与这一预测一致,我们发现多巴胺会使突触隔离的PY神经元的净电导降低。在电压钳实验中,多巴胺会降低IA,具体方式是降低电流中缓慢失活成分的幅度,并使其电压激活曲线向去极化方向移动。4-氨基吡啶是口胃神经元中IA的选择性阻断剂,它模拟并阻断了多巴胺对分离的PY神经元的作用。基于电导的PY神经元数学模型表明,在对受多巴胺影响的IA参数进行定量修改后,神经元活动会发生适当变化。这些结果表明,多巴胺至少部分地通过降低瞬时钾电流IA,来激发并使PY神经元在节律性幽门运动模式中的活动时间提前。