ASIC1a channels regulate mitochondrial ion signaling and energy homeostasis in neurons

Ivana Savic Azoulay, Fan Liu, Qin Hu, Maya Rozenfeld, Tsipi Ben Kasus Nissim, Michael X. Zhu, Israel Sekler, Tian Le Xu

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Acid-sensing ion channel 1a (ASIC1a) is well-known to play a major pathophysiological role during brain ischemia linked to acute acidosis of ~pH 6, whereas its function during physiological brain activity, linked to much milder pH changes, is still poorly understood. Here, by performing live cell imaging utilizing Na+ and Ca2+ sensitive and spatially specific fluorescent dyes, we investigated the role of ASIC1a in cytosolic Na+ and Ca2+ signals elicited by a mild extracellular drop from pH 7.4 to 7.0 and how these affect mitochondrial Na+ and Ca2+ signaling or metabolic activity. We show that in mouse primary cortical neurons, this small extracellular pH change triggers cytosolic Na+ and Ca2+ waves that propagate to mitochondria. Inhibiting ASIC1a with Psalmotoxin 1 or ASIC1a gene knockout blocked not only the cytosolic but also the mitochondrial Na+ and Ca2+ signals. Moreover, physiological activation of ASIC1a by this pH shift enhances mitochondrial respiration and evokes mitochondrial Na+ signaling even in digitonin-permeabilized neurons. Altogether our results indicate that ASIC1a is critical in linking physiological extracellular pH stimuli to mitochondrial ion signaling and metabolic activity and thus is an important metabolic sensor. (Figure presented.).

Original languageEnglish
Pages (from-to)203-215
Number of pages13
JournalJournal of Neurochemistry
Volume153
Issue number2
DOIs
StatePublished - 1 Apr 2020

Keywords

  • ASIC1a
  • NCLX
  • cytosolic Ca signaling
  • cytosolic Na signaling
  • mitochondrial Ca signaling
  • mitochondrial Na signaling

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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