| First Author | Savic Azoulay I | Year | 2020 |
| Journal | J Neurochem | Volume | 153 |
| Issue | 2 | Pages | 203-215 |
| PubMed ID | 31976561 | Mgi Jnum | J:294272 |
| Mgi Id | MGI:6455395 | Doi | 10.1111/jnc.14971 |
| Citation | Savic Azoulay I, et al. (2020) ASIC1a channels regulate mitochondrial ion signaling and energy homeostasis in neurons. J Neurochem 153(2):203-215 |
| abstractText | 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. |
