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ASIC1a channels regulate mitochondrial ion signaling and energy homeostasis in neurons
Author(s) -
Savic Azoulay Ivana,
Liu Fan,
Hu Qin,
Rozenfeld Maya,
Ben Kasus Nissim Tsipi,
Zhu Michael X.,
Sekler Israel,
Xu TianLe
Publication year - 2020
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.14971
Subject(s) - extracellular , microbiology and biotechnology , cytosol , mitochondrion , ion channel , biology , acid sensing ion channel , homeostasis , biochemistry , digitonin , biophysics , chemistry , receptor , membrane , enzyme
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 Ca 2+ sensitive and spatially specific fluorescent dyes, we investigated the role of ASIC1a in cytosolic Na + and Ca 2+ signals elicited by a mild extracellular drop from pH 7.4 to 7.0 and how these affect mitochondrial Na + and Ca 2+ signaling or metabolic activity. We show that in mouse primary cortical neurons, this small extracellular pH change triggers cytosolic Na + and Ca 2+ 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 Ca 2+ 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.