کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
4339805 | 1295768 | 2009 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
New insights on the role of gephyrin in regulating both phasic and tonic GABAergic inhibition in rat hippocampal neurons in culture
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کلمات کلیدی
PBSNLSVGATmIPSCseGFPDNQXscFvFCSTTX6,7-dinitroquinoxaline-2,3-dione - 6،7-dinitroquinoxaline-2،3-dioneBSA - BSADMSO - DMSObovine serum albumin - آلبومین سرم گاوRecombinant antibodies - آنتیبادی های بازآفرینیγ-aminobutyric acid - اسید γ-آمینوبوتیریکImmunocytochemistry - ایمونوسیتوشیمیtetrodotoxin - تترو دوتوکسین miniature inhibitory postsynaptic currents - جریان ممانعت کننده پسینپتیکvesicular GABA transporter - حامل ویسکوزر GABADimethylsulfoxide - دیمتیل سولفواکسیدfetal calf serum - سرم گوساله جنینnuclear localization signal - سیگنال محلی سازی هسته ایPhosphate-buffered saline - محلول نمک فسفات با خاصیت بافریenhanced green fluorescent protein - پروتئین فلورسنت سبز افزایش یافته استGABA - گابا
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
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چکیده انگلیسی
Gephyrin is a tubulin-binding protein that acts as a scaffold for clustering glycine and GABAA receptors at postsynaptic sites. In this study, the role of gephyrin on GABAA receptor function was assessed at the post-translational level, using gephyrin-specific single chain antibody fragments (scFv-gephyrin). When expressed in cultured rat hippocampal neurons as a fusion protein containing a nuclear localization signal, scFv-gephyrin were able to remove endogenous gephyrin from GABAA receptor clusters. Immunocytochemical experiments revealed a significant reduction in the number of synaptic γ2-subunit containing GABAA receptors and a significant decrease in the density of the GABAergic presynaptic marker vesicular GABA transporter (VGAT). These effects were associated with a slow down of the onset kinetics, a reduction in the amplitude and in the frequency of miniature inhibitory postsynaptic currents (mIPSCs). The quantitative analysis of current responses to ultrafast application of GABA suggested that changes in onset kinetics resulted from modifications in the microscopic gating of GABAA receptors and in particular from a reduced entry into the desensitized state. In addition, hampering gephyrin function with scFv-gephyrin induced a significant reduction in GABAA receptor-mediated tonic conductance. This effect was probably dependent on the decrease in GABAergic innervation and in GABA release from presynaptic nerve terminals. These results indicate that gephyrin is essential not only for maintaining synaptic GABAA receptor clusters in the right position but also for regulating both phasic and tonic inhibition.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 164, Issue 2, 1 December 2009, Pages 552-562
Journal: Neuroscience - Volume 164, Issue 2, 1 December 2009, Pages 552-562
نویسندگان
I. Marchionni, Z. Kasap, J.W. Mozrzymas, W. Sieghart, E. Cherubini, P. Zacchi,