Shi Hai-Bo, Kakazu Yasuhiro, Shibata Shumei, Matsumoto Nozomu, Nakagawa Takashi, Komune Shizuo
Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Neurosci Res. 2006 Jun;55(2):161-70. doi: 10.1016/j.neures.2006.02.015. Epub 2006 Apr 3.
Bilirubin is a well-known neurotoxin that can result in multiple neurologic deficits. Previous studies have suggested that bilirubin affects aspects of synaptic transmission; however the acute effects of bilirubin on synaptic transmission have not been examined in real-time. In this study, using whole-cell voltage-clamp recordings, we observed the effect of bilirubin on inhibitory postsynaptic currents (IPSC) in postnatal 13-15-day-old neurons dissociated from lateral superior olive nuclei (LSO), one of the brainstem auditory nucleus that are highly vulnerable to bilirubin. The results showed that 10(-5)M bilirubin increased the frequency of spontaneous IPSC without causing change in their amplitudes or in the response to bath applied glycine, suggesting a presynaptic locus for the action. In the presence of tetrodotoxin, the frequency of miniature IPSC was also potentiated by 10(-5)M bilirubin. The facilitation by bilirubin was concentration dependent and increased with an increase in exposure time. Bicuculline only partially reduced the action of bilirubin. The action of bilirubin was observed in extracellular Ca(2+)-free (Ca(2+) free) solution but was fully occluded by pretreatment with BAPTA-AM in Ca(2+) free solution. Thus, in LSO neurons, bilirubin facilitates inhibitory synaptic transmission, in a manner independent of voltage-activated Na(+) and Ca(2+) channels but dependent on presynaptic Ca(2+). The increase of inhibitory synaptic transmission in response to acute bilirubin is a novel effect of bilirubin on the central nervous system and may have implications for neurotoxicity and the impairment of auditory transduction seen in hyperbilirubinemia.
胆红素是一种众所周知的神经毒素，可导致多种神经功能缺损。以往的研究表明，胆红素会影响突触传递的多个方面；然而，胆红素对突触传递的急性影响尚未进行实时研究。在本研究中，我们使用全细胞电压钳记录，观察了胆红素对从外侧上橄榄核（LSO）解离的出生后13 - 15天龄神经元中抑制性突触后电流（IPSC）的影响，LSO是脑干听觉核之一，对胆红素高度敏感。结果表明，10^(-5)M胆红素增加了自发性IPSC的频率，而不改变其幅度或对浴应用甘氨酸的反应，提示作用位点在突触前。在存在河豚毒素的情况下，10^(-5)M胆红素也增强了微小IPSC的频率。胆红素的促进作用呈浓度依赖性，并随暴露时间的增加而增强。荷包牡丹碱仅部分降低了胆红素的作用。在无细胞外Ca(2+)（[Ca(2+)]o游离）溶液中观察到了胆红素的作用，但在[Ca(2+)]o游离溶液中用BAPTA - AM预处理可完全阻断其作用。因此，在LSO神经元中，胆红素以独立于电压激活的Na(+)和Ca(2+)通道但依赖于突触前[Ca(2+)]i的方式促进抑制性突触传递。急性胆红素引起的抑制性突触传递增加是胆红素对中枢神经系统的一种新作用，可能与高胆红素血症中所见的神经毒性和听觉转导受损有关。
