Acid sensing ionic channels: Modulation by redox reagents

Acid sensing ionic channels: Modulation by redox reagents
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DOI:
10.1016/j.bbamcr.2005.01.008
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发表时间:
2005-08-15
影响因子:
5.1
通讯作者:
Krishtal, O
Krishtal, O
中科院分区:
生物学2区
文献类型:
--
作者:
Andrey, F;Tsintsadze, T;Krishtal, O

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酸敏感离子通道(ASICs)在哺乳动物感觉神经元中广泛表达,并被认为在伤害感受和酸敏感中起作用。在功能的过程中,组织的氧化还原状态发生变化。采用全细胞膜片钳/浓度钳技术研究了氧化还原试剂对大鼠感觉神经节和海马神经元ASIC样电流的影响。还原剂二硫苏糖醇(DTT),当以1-2 mM的浓度应用时,可逆地增强质子激活电流,而氧化剂5,5-二硫代-双-(2-硝基苯甲酸)(DTNB)导致其抑制。质子激活类ASIC电流的EC_(50)和Hill系数不受DTT的影响。质子激活电流的氧化还原调制是独立的膜电位和用于电流激活的pH值的水平上。内源性抗氧化剂三肽谷胱甘肽(其还原形式,g-L-谷氨酰-L-半胱氨酰-甘氨酸,GSH)也可增强质子激活电流。我们的研究结果表明,ASIC样电流容易受到氧化还原剂的调节。(c)2005 Elsevier B.V保留所有权利。
Acid-sensing ion channels (ASICs) are widely expressed in mammalian sensory neurons and supposedly play a role in nociception and acid sensing. In the course of functioning the redox status of the tissue is subjected to changes. Using whole-cell patch-clamp/concentration clamp techniques we have investigated the effect of redox reagents on the ASIC-like currents in the sensory ganglia and hippocampal neurons of rat. The reducing agent dithiothreitol (DTT), when applied in the concentrations 1-2 mM, reversibly potentiates proton-activated currents, while the oxidizing reagent 5,5-dithio-bis-(2-nitrobenzoic acid) (DTNB) causes their inhibition. The EC50 and Hill coefficient for the activation of ASIC-like currents by protons are not affected by DTT. Redox modulation of proton-activated currents is independent on the membrane potential and on the level of pH used for the current activation. The endogenous antioxidant tripeptide glutathione (its reduced form, g-L-glutamyl-L-cysteinyl-glycine, GSH) also potentiates proton-activated currents. Our results indicate that ASIC-like currents are susceptible to regulation by redox agents. (c) 2005 Elsevier B.V All rights reserved.