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α-树突毒素抑制大鼠背根神经节神经元中的酸敏感离子通道电流。

α-Dendrotoxin inhibits the ASIC current in dorsal root ganglion neurons from rat.

作者信息

Báez Adriana, Salceda Emilio, Fló Martín, Graña Martín, Fernández Cecilia, Vega Rosario, Soto Enrique

机构信息

Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla (BUAP), 14 sur 6301, CU, San Manuel, Puebla, Pue., CP 72570, Mexico.

Faculty of Chemistry, UDELAR, Av. Gral., Flores, Montevideo 2124, Uruguay.

出版信息

Neurosci Lett. 2015 Oct 8;606:42-7. doi: 10.1016/j.neulet.2015.08.034. Epub 2015 Aug 24.

Abstract

Dendrotoxins are a group of peptide toxins purified from the venom of several mamba snakes. α-Dendrotoxin (α-DTx, from the Eastern green mamba Dendroaspis angusticeps) is a well-known blocker of voltage-gated K(+) channels and specifically of K(v)1.1, K(v)1.2 and K(v)1.6. In this work we show that α-DTx inhibited the ASIC currents in DRG neurons (IC50=0.8 μM) when continuously perfused during 25 s (including a 5 s pulse to pH 6.1), but not when co-applied with the pH drop. Additionally, we show that α-DTx abolished a transient component of the outward current that, in some experiments, appeared immediately after the end of the acid pulse. Our data indicate that α-DTx inhibits ASICs in the high nM range while some Kv are inhibited in the low nM range. The α-DTx selectivity and its potential interaction with ASICs should be taken in consideration when DTx is used in the high nM range.

摘要

树眼镜蛇毒素是从几种曼巴蛇毒液中纯化出来的一组肽毒素。α-树眼镜蛇毒素(α-DTx,来自东部绿曼巴蛇黑曼巴)是一种著名的电压门控钾通道阻滞剂,特别是对K(v)1.1、K(v)1.2和K(v)1.6通道。在这项研究中,我们发现,当在25秒内持续灌注(包括向pH 6.1的5秒脉冲)时,α-DTx可抑制背根神经节神经元中的酸敏感离子通道电流(IC50 = 0.8 μM),但与pH下降共同应用时则不然。此外,我们还发现,α-DTx消除了外向电流的一个瞬态成分,在某些实验中,该成分在酸脉冲结束后立即出现。我们的数据表明,α-DTx在高纳摩尔范围内抑制酸敏感离子通道,而一些钾通道在低纳摩尔范围内受到抑制。当在高纳摩尔范围内使用树眼镜蛇毒素时,应考虑其对酸敏感离子通道的选择性及其潜在相互作用。

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