Andrey Fedorenko, Tsintsadze Timur, Volkova Tatyana, Lozovaya Natalia, Krishtal Oleg
Department of Cellular Membranology, Bogomoletz Institute of Physiology, Kiev, Ukraine.
Biochim Biophys Acta. 2005 Aug 15;1745(1):1-6. doi: 10.1016/j.bbamcr.2005.01.008. Epub 2005 Feb 24.
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.
酸敏感离子通道（ASICs）在哺乳动物感觉神经元中广泛表达，据推测在痛觉感受和酸感知中发挥作用。在组织功能运作过程中，其氧化还原状态会发生变化。我们运用全细胞膜片钳/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中ASIC样电流的影响。还原剂二硫苏糖醇（DTT）在1 - 2 mM浓度下应用时，可使质子激活电流可逆性增强，而氧化剂5,5'-二硫代双（2 - 硝基苯甲酸）（DTNB）则会导致电流受到抑制。质子激活ASIC样电流的半数有效浓度（EC5）和希尔系数不受DTT影响。质子激活电流的氧化还原调节与膜电位以及用于电流激活的pH水平无关。内源性抗氧化三肽谷胱甘肽（其还原形式，γ-L-谷氨酰-L-半胱氨酰-甘氨酸，GSH）也能增强质子激活电流。我们的结果表明，ASIC样电流易受氧化还原试剂的调节。
