ASIC1a channels regulate mitochondrial ion signaling and energy homeostasis in neurons
| Autor: | Michael X. Zhu, Maya Rozenfeld, Fan Liu, Tian-Le Xu, Tsipi Ben Kasus Nissim, Ivana Savic Azoulay, Qin Hu, Israel Sekler |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Mitochondrion Biochemistry Article Energy homeostasis Mice 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Live cell imaging Psalmotoxin Extracellular Animals Homeostasis Ion channel Gene knockout Cerebral Cortex Mice Knockout Neurons Hydrogen-Ion Concentration Mitochondria Cell biology Acid Sensing Ion Channels Mice Inbred C57BL Cytosol 030104 developmental biology chemistry Energy Metabolism 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | J Neurochem |
| ISSN: | 1471-4159 0022-3042 |
| DOI: | 10.1111/jnc.14971 |
| Popis: | 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, while 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 (PcTX1) 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. |
| Databáze: | OpenAIRE |
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