کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8525720 | 1557941 | 2018 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
GIRK1-mediated inwardly rectifying potassium current suppresses the epileptiform burst activities and the potential antiepileptic effect of ML297
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کلمات کلیدی
PTZAMPARTTXKCC2CTZTPQγ-aminobutyric acid - اسید γ-آمینوبوتیریکkainic acid - اسید کرییکtetrodotoxin - تترو دوتوکسین inwardly rectifying potassium channel - درون کانال پتاسیم اصلاح شده استcyclothiazide - سیکلوتیازیدpentylenetetrazol - پنتیلن تترازولGIRK channel - کانال GIRKKir channel - کانال کیرGABA - گاباAMPA receptor - گیرنده AMPA
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
تومور شناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
G protein-gated inwardly rectifying potassium (GIRK) channels are important inhibitory regulators of neuronal excitability in central nervous system, and the impairment of GIRK channel function has been reported to be associated with the susceptibility of epilepsy. However, the dynamics of GIRK channels in the pathogenesis of epilepsy are still unclear. In this study, our results showed that cyclothiazide, a potent convulsant, dose dependently increased the epileptiform bursting activities and suppressed the baclofen induced GIRK currents. In addition, TPQ, a selective GIRK antagonist, significantly decreased the total inwardly rectifying potassium (Kir) current, and increased the neuronal epileptiform activities. In contrast, ML297, a potent and selective GIRK channel agonist, reversed the cyclothiazide induced decrease of GIRK currents and the increase of neuronal excitability in cultured hippocampal neurons. Further investigation revealed that GIRK1, but not GIRK2, played a key role in suppressing epileptic activities. Finally, in pilocarpine mice seizure model, we demonstrated that ML297 significantly suppressed the seizure behavior. In summary, our current results indicate that GIRK channels, especially GIRK1-containing channels, are involved in epileptic activities and ML297 has a potential antiepileptic effect.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biomedicine & Pharmacotherapy - Volume 101, May 2018, Pages 362-370
Journal: Biomedicine & Pharmacotherapy - Volume 101, May 2018, Pages 362-370
نویسندگان
Yian Huang, Yuwen Zhang, Shuzhen Kong, Kai Zang, Shize Jiang, Li Wan, Lulan Chen, Guoxiang Wang, Min Jiang, Xin Wang, Jie Hu, Yun Wang,