Cellular and Molecular Neurobiology
Author: Libia Catalina Salinas Castellanos | Email: licasaca@gmail.com
Libia Catalina Salinas Castellanos1°, Mayra Montes1°, Georgina Mingolo1°2°, Carina Weissmann1°
1° IFIBYNE-UBA-CONICET, Buenos Aires, Argentina
2° Cátedra de Histología y Embriología, Facultad de Odontología, UBA, Buenos Aires, Argentina
Perturbations in brain pH levels are commonly observed in neurodegenerative disorders and can activate ASICs. Among these, ASIC1a, a pH-sensitive sodium channel, has been implicated in several pathophysiology conditions, characterized by neuroinflammation and elevated levels of interleukin-6 in the central nervous system. We analyzed the interaction between IL-6 and ASIC1a channels. We found that IL-6 promotes the translocation of ASIC1a from cytosolic compartments to the plasma membrane. Once at the membrane, ASIC1a activation initiates critical signaling pathways, including calcium/calmodulin-dependent protein kinase II (CaMKII) and extracellular signal-regulated kinase (ERK).Pre-incubation with IL-6 significantly amplified the phosphorylation of CaMKII and ERK upon ASIC1a activation by MitTx, a specific ASIC1a toxin. IL-6 and MitTx also induced morphological changes in HEK cells, such as membrane blebbing, which were mitigated by ERK inhibition or ASIC1a blockade. Notably, neurons exposed to a pH of 6.5 exhibited morphological alterations after just a few minutes, which could be prevented by the ASIC1a inhibitor Pctx-1.These findings highlight the complex crosstalk between IL-6, pH dysregulation, and ASIC1a channels, offering new insights into the mechanisms underlying neuroinflammation and neurodegeneration. Understanding these interactions could lead to novel therapeutic strategies in neuroinflammatory conditions.