Vatanparast Jafar, Khalili Samira, Naseh Maryam
Department of Biology, College of Science, Shiraz University, Shiraz, Iran.
Department of Biology, College of Science, Shiraz University, Shiraz, Iran.
Neurotoxicology. 2017 Jan;58:84-91. doi: 10.1016/j.neuro.2016.11.011. Epub 2016 Nov 25.
Besides its well-known actions on sensory afferents, eugenol also affects general excitability of the nervous system, but the mechanisms involved in the recent effect, especially through modulation of ion channels, have received much less attention. In this study, we studied the effects of eugenol on the excitability of central neurons of land snail Caucasotachea atrolabiata and tried to elucidate the underlying ionic mechanisms. The lower concentration of eugenol (0.5mM) reversibly reduced the frequency of spontaneous action potentials that was associated with elevation of threshold, reduction of maximum slope of rising phase and prolongation of actin potentials. These effects were mimicked by riluzole, suggesting that they might be mediated by inhibition of Na channels. Eugenol also prolonged the single-spike afterhyperpolarization and post stimulus inhibitory period, but these effects seemed to be consequent to action potential prolongation that indirectly augment Ca inward currents and Ca-activated K currents. This concentration of eugenol was also able to prevent or abolish pentylenetetrazole-induced epileptiform activity. On the other hand, a higher concentration of eugenol (2mM) reversibly increased the frequency of action potentials and then induced epileptiform activity in majority of treated neurons. Several criteria suggest that the inhibition of K channels by higher concentration of eugenol and indirect augmentation of Ca currents are central to the hyperexcitability and epileptiform activity induced by eugenol. Our findings indicate that while low concentration of eugenol could have antiepileptic properties, at higher concentration it induces epileptiform activity. It seems that does dependent inhibition of the ionic currents underlying rising and falling phases of action potential is relevant to the eugenol suppressant and excitatory actions, respectively.
除了其对感觉传入神经的众所周知的作用外，丁香酚还会影响神经系统的一般兴奋性，但最近这种作用所涉及的机制，尤其是通过离子通道调节的机制，受到的关注要少得多。在本研究中，我们研究了丁香酚对陆地蜗牛高加索阿特罗拉比阿塔中枢神经元兴奋性的影响，并试图阐明其潜在的离子机制。较低浓度的丁香酚（0.5mM）可逆地降低了自发动作电位的频率，这与阈值升高、上升相最大斜率降低和动作电位延长有关。利鲁唑可模拟这些效应，表明它们可能是由钠通道抑制介导的。丁香酚还延长了单峰后超极化和刺激后抑制期，但这些效应似乎是动作电位延长的结果，动作电位延长间接增加了钙内向电流和钙激活钾电流。这种浓度的丁香酚也能够预防或消除戊四氮诱导的癫痫样活动。另一方面，较高浓度的丁香酚（2mM）可逆地增加了动作电位的频率，然后在大多数处理过的神经元中诱导出癫痫样活动。几个标准表明，较高浓度的丁香酚对钾通道的抑制和钙电流的间接增加是丁香酚诱导的兴奋性过高和癫痫样活动的核心。我们的研究结果表明，低浓度的丁香酚可能具有抗癫痫特性，而高浓度时则会诱导癫痫样活动。似乎动作电位上升和下降阶段潜在的离子电流的剂量依赖性抑制分别与丁香酚的抑制和兴奋作用有关。
