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PubMed · 16085050

Acid sensing ionic channels: modulation by redox reagents.

Fedorenko Andrey·Timur Tsintsadze·Tatyana Volkova·Natalia Lozovaya·Oleg Krishtal
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Abstract

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.

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Acid Sensing Ion ChannelsAnimalsCalciumDithionitrobenzoic AcidGlutathioneHippocampusHydrogen-Ion ConcentrationIndicators and ReagentsMembrane ProteinsNerve Tissue ProteinsOxidation-ReductionPyramidal CellsRatsRats, WistarSodiumSodium ChannelsJournal ArticleResearch Support, Non-U.S. Gov't

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Fedorenko Andrey, Timur Tsintsadze, Tatyana Volkova, Natalia Lozovaya, Oleg Krishtal. 2005-02-24. Acid sensing ionic channels: modulation by redox reagents.. https://doi.org/10.1016/j.bbamcr.2005.01.008

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Acid Sensing Ion Channels↗
PubMed2007

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Acid-sensing ion channels (ASICs) are known to distribute throughout the nervous system and serve important roles in various physiological and pathological processes. However, the properties of ASICs in the hypothalamus, an important region of diencephalon, are little known. We herein used whole-cell patch-clamp recordings to characterize proton-induced cation currents in cultured hypothalamic neurons of the rat, and attributed these transient inward currents to ASICs based on their electrophysiological and pharmacological properties. We further examined the effects of Cu(2+), the third most abundant trace element, on ASICs in hypothalamic neurons. Our results showed that this divalent cation reversibly and concentration-dependently inhibited the amplitude of ASIC currents, and slowed down the desensitization of ASIC channels. Our results also displayed that Cu(2+) modulated ASICs independent of change in membrane potential and extracellular protons, suggesting a noncompetitive mechanism. Furthermore, micromolar concentration of Cu(2+) attenuated the acid-induced membrane depolarization. Taken together, our data demonstrate a modulatory effect of Cu(2+) on ASICs in native hypothalamic neurons and suggest a role of this endogenous metal ion in negatively modulating the increased neuronal membrane excitability caused by activation of ASICs.

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