质子入的Ca2+) 透的TRP通道在模仿缺血症的条件下损害髓
Nicola B Hamilton1, Karolina Kolodziejczyk1, Eleni Kougioumtzidou1
1Department of Neuroscience, Physiology &Pharmacology, University College London, Gower St., London WC1E 6BT, UK.
Nature
|January 14, 2016
概括
缺血症会损害大脑中的髓蛋白,但不是通过NMDA受体. 相反,细胞内酸度增加会激活TRPA1通道,提高水平并损害髓,这表明TRPA1是治疗点.
科学领域:
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 氧基细胞产生髓膜,这对大脑功能至关重要.
- 缺血导致髓损伤,损害了动作潜力的传播.
- 这种损伤以前归因于N-甲基-D-阿斯巴达酸 (NMDA) 受体的激活.
研究的目的:
- 为了研究在缺血期间的寡腺细胞损伤的机制.
- 为了确定参与细胞内在缺血期间增加的离子通道.
- 探索白质缺血的潜在治疗点.
主要方法:
- 电生理学测量膜电流和细胞内离子度 ([Ca2+) ]i,[Mg2+) ]i,[H2+) ]i).
- 药物抑制和TRPA1通道的遗传淘汰.
- 在有或没有TRPA1抑制的缺血性疾病中评估髓损伤.
主要成果:
- 在缺血期间,NMDA在成熟的寡细胞中没有增加细胞内.
- 缺血症通过细胞外的增加和电导率的降低诱导了由谷氨酸触发的电流.
- 细胞内酸化 ([H(+) 的增加) i) 通过TRPA1通道触发了和的流入,导致髓损伤.
- 抑制TRPA1通道可以减少缺血症中的髓损伤.
结论:
- 缺血中寡细胞损伤的机制涉及细胞内酸性激活TRPA1通道,而不是NMDA受体.
- 在白质缺血期间,TRPA1通道是和流入的关键媒介.
- 含有TRPA1的离子通道是治疗白质缺血的有希望的治疗点.
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