Yvon Cédric, Czarnecki Antonny, Streit Jürg
Department of Physiology, University of Bern, Switzerland.
J Neurophysiol. 2007 May;97(5):3607-20. doi: 10.1152/jn.00924.2006. Epub 2007 Mar 7.
We previously showed in dissociated cultures of fetal rat spinal cord that disinhibition-induced bursting is based on intrinsic spiking, network recruitment, and a network refractory period after the bursts. A persistent sodium current (I(NaP)) underlies intrinsic spiking, which, by recurrent excitation, generates the bursting activity. Although full blockade of I(NaP) with riluzole disrupts such bursting, the present study shows that partial blockade of I(NaP) with low doses of riluzole maintains bursting activity with unchanged burst rate and burst duration. More important, low doses of riluzole turned bursts composed of persistent activity into bursts composed of oscillatory activity at around 5 Hz. In a search for the mechanisms underlying the generation of such intraburst oscillations, we found that activity-dependent synaptic depression was not changed with low doses of riluzole. On the other hand, low doses of riluzole strongly increased spike-frequency adaptation and led to early depolarization block when bursts were simulated by injecting long current pulses into single neurons in the absence of fast synaptic transmission. Phenytoin is another I(NaP) blocker. When applied in doses that reduced intrinsic activity by 80-90%, as did low doses of riluzole, it had no effect either on spike-frequency adaptation or on depolarization block. Nor did phenytoin induce intraburst oscillations after disinhibition. A theoretical model incorporating a depolarization block mechanism could reproduce the generation of intraburst oscillations at the network level. From these findings we conclude that riluzole-induced intraburst oscillations are a network-driven phenomenon whose major accommodation mechanism is depolarization block arising from strong sodium channel inactivation.
我们之前在胎鼠脊髓的解离培养物中发现，去抑制诱导的爆发是基于内在的放电、网络募集以及爆发后的网络不应期。一种持续性钠电流（I(NaP)）是内在放电的基础，通过反复兴奋产生爆发活动。虽然用利鲁唑完全阻断I(NaP)会破坏这种爆发，但本研究表明，低剂量利鲁唑部分阻断I(NaP)时，爆发活动得以维持，爆发频率和持续时间不变。更重要的是，低剂量利鲁唑使由持续性活动组成的爆发转变为由约5Hz振荡活动组成的爆发。在探寻这种爆发内振荡产生机制的过程中，我们发现低剂量利鲁唑并未改变活动依赖性突触抑制。另一方面，低剂量利鲁唑显著增强了放电频率适应性，并且在无快速突触传递的情况下向单个神经元注入长电流脉冲模拟爆发时，会导致早期去极化阻滞。苯妥英是另一种I(NaP)阻断剂。当以与低剂量利鲁唑相同的剂量应用，使内在活动降低80 - 90%时，它对放电频率适应性或去极化阻滞均无影响。苯妥英在去抑制后也不会诱导爆发内振荡。一个纳入去极化阻滞机制的理论模型能够在网络层面重现爆发内振荡的产生。从这些发现我们得出结论，利鲁唑诱导的爆发内振荡是一种网络驱动现象，其主要调节机制是由强钠通道失活引起的去极化阻滞。
