Activation of acid-sensing ion channels by localized proton transient reveals their role in proton signaling

Wei Zheng Zeng, Di Shi Liu, Lu Liu, Liang She, Long Jun Wu, Tian Le Xu

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Extracellular transients of pH alterations likely mediate signal transduction in the nervous system. Neuronal acid-sensing ion channels (ASICs) act as sensors for extracellular protons, but the mechanism underlying ASIC activation remains largely unknown. Here, we show that, following activation of a light-activated proton pump, Archaerhodopsin-3 (Arch), proton transients induced ASIC currents in both neurons and HEK293T cells co-expressing ASIC1a channels. Using chimera proteins that bridge Arch and ASIC1a by a glycine/serine linker, we found that successful coupling occurred within 15 nm distance. Furthermore, two-cell sniffer patch recording revealed that regulated release of protons through either Arch or voltage-gated proton channel Hv1 activated neighbouring cells expressing ASIC1a channels. Finally, computational modelling predicted the peak proton concentration at the intercellular interface to be at pH 6.7, which is acidic enough to activate ASICs in vivo. Our results highlight the pathophysiological role of proton signalling in the nervous system.

Original languageEnglish (US)
Article number14125
JournalScientific reports
Volume5
DOIs
StatePublished - Sep 15 2015

ASJC Scopus subject areas

  • General

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