کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5814009 | 1556621 | 2015 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Snake neurotoxin α-bungarotoxin is an antagonist at native GABAA receptors
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کلمات کلیدی
PFAIPSCsnAChRsα-bungarotoxinGABAARsd-Tcα-BgTxd-tubocurarine - D-tubocurarineElectrophysiology - الکتروفیزیولوژیImmunofluorescence - ایمونوفلورسانسSpontaneous inhibitory postsynaptic currents - جریانهای پسینپتیک مهار کننده خود به خودیdentate gyrus - شکنج دندانه دارparaformaldehyde - پارافرمالدهیدGABA receptor - گیرنده GABAnicotinic acetylcholine receptor - گیرنده استیلکولین نیکوتینnicotinic acetylcholine receptors - گیرنده های استیل کولین نیکوتین
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
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چکیده انگلیسی
The snake neurotoxin α-bungarotoxin (α-Bgtx) is a competitive antagonist at nicotinic acetylcholine receptors (nAChRs) and is widely used to study their function and cell-surface expression. Increasingly, α-Bgtx is also used as an imaging tool for fluorophore-labelling studies, and given the structural conservation within the pentameric ligand-gated ion channel family, we assessed whether α-Bgtx could bind to recombinant and native γ-aminobutyric type-A receptors (GABAARs). Applying fluorophore-linked α-Bgtx to recombinant αxβ1/2γ2 GABAARs expressed in HEK-293 cells enabled clear cell-surface labelling of α2β1/2γ2 contrasting with the weaker staining of α1/4β1/2γ2, and no labelling for α3/5/6β1/2γ2. The labelling of α2β2γ2 was abolished by bicuculline, a competitive antagonist at GABAARs, and by d-tubocurarine (d-Tc), which acts in a similar manner at nAChRs and GABAARs. Labelling by α-Bgtx was also reduced by GABA, suggesting that the GABA binding site at the receptor β-α subunit interface forms part of the α-Bgtx binding site. Using whole-cell recording, high concentrations of α-Bgtx (20 μM) inhibited GABA-activated currents at all αxβ2γ2 receptors examined, but at lower concentrations (5 μM), α-Bgtx was selective for α2β2γ2. Using α-Bgtx, at low concentrations, permitted the selective inhibition of α2 subunit-containing GABAARs in hippocampal dentate gyrus granule cells, reducing synaptic current amplitudes without affecting the GABA-mediated tonic current. In conclusion, α-Bgtx can act as an inhibitor at recombinant and native GABAARs and may be used as a selective tool to inhibit phasic but not tonic currents in the hippocampus.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 93, June 2015, Pages 28-40
Journal: Neuropharmacology - Volume 93, June 2015, Pages 28-40
نویسندگان
Saad Hannan, Martin Mortensen, Trevor G. Smart,