کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2494920 | 1115586 | 2008 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Inhibition of NMDA-gated ion channels by bis(7)-tacrine: Whole-cell and single-channel studies
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
NMDAN-methyl-d-aspartateNMDA receptor - NMDA گیرندهAChE - آهیAcetylcholinesterase - استیل کولین استرازElectrophysiology - الکتروفیزیولوژیBis(7)-tacrine - بیس (7) -تکرینAlzheimer's disease - بیماری آلزایمرanalysis of variance - تحلیل واریانسANOVA - تحلیل واریانس Analysis of varianceacetylcholinesterase inhibitor - مهارکننده استیل کولین استرازGlutamate receptor - گیرنده گلومات
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Inhibition of NMDA-gated ion channels by bis(7)-tacrine: Whole-cell and single-channel studies Inhibition of NMDA-gated ion channels by bis(7)-tacrine: Whole-cell and single-channel studies](/preview/png/2494920.png)
چکیده انگلیسی
Bis(7)-tacrine is a novel dimeric acetylcholinesterase inhibitor derived from tacrine, and has been proposed as a promising agent to treat Alzheimer's disease. We have recently reported that bis(7)-tacrine prevents glutamate-induced neuronal apoptosis by antagonizing NMDA receptors. The purpose of this study was to characterize bis(7)-tacrine inhibition of NMDA-activated current by using patch-clamp recording techniques. In cultured rat hippocampal neurons, bis(7)-tacrine inhibited NMDA-activated whole-cell current in a concentration-dependent manner with an IC50 of 0.66 ± 0.07 μM. Bis(7)-tacrine produced a gradual decline of NMDA-activated current to a steady-state, but this was not an indication of use-dependence. Also, the slow onset of inhibition by bis(7)-tacrine was not apparently due to an action at an intracellular site. Bis(7)-tacrine, 0.5 μM, decreased the maximal response to NMDA by 40% without changing its EC50. Bis(7)-tacrine inhibition of NMDA-activated current was not voltage-dependent, and was independent of glycine concentration. Results of single-channel experiments obtained from cells expressing NR1 and NR2A subunits revealed that bis(7)-tacrine decreased the open probability and frequency of channel opening, but did not significantly alter the mean open time or introduce rapid closures. These results suggest that bis(7)-tacrine can inhibit NMDA receptor function in a manner that is slow in onset and offset and noncompetitive with respect to both NMDA and glycine. The noncompetitive inhibition of NMDA receptors by bis(7)-tacrine could contribute to its protective effect against glutamate-induced neurotoxicity.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 54, Issue 7, June 2008, Pages 1086-1094
Journal: Neuropharmacology - Volume 54, Issue 7, June 2008, Pages 1086-1094
نویسندگان
Yu-Wei Liu, Jia-Lie Luo, Hong Ren, Robert W. Peoples, Yong-Xun Ai, Li-Jiang Liu, Yuan-Ping Pang, Zhi-Wang Li, Yi-Fan Han, Chao-Ying Li,