Redistribution of ASIC1a channels triggered by IL-6: Potential role of ASIC1a in neuroinflammation

CASTELLANOS, LIBIA CATALINA SALINAS; GATTO, RODOLFO GABRIEL; MALNATI, GEORGINA ORIANA MINGOLO; MONTES, MAYRA MICAELA; UCHITEL, OSVALDO DANIEL; WEISSMANN, CARINA

BIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR BASIS OF DISEASE

ELSEVIER SCIENCE BV

Año: 2024 vol. 1870

0925-4439

Cytokines, particularly IL-6, play a crucial role in modulating immune responses in the central nervous system (CNS). Elevated IL-6 levels have been observed in neuroinflammatory conditions, as well as in the sera and brains of patients with neurodegenerative diseases such as Parkinson´s, Huntington´s, Multiple Sclerosis, and Alzheimer´s. Additionally, alterations in regional brain pH have been noted in these conditions. Acid-sensing ion channels (ASICs), including ASIC1a, activated by low pH levels, are highly abundant in the CNS and have recently been associated with various neurological disorders. Our study examined the impact of IL-6 on ASIC1a channels in cell cultures, demonstrating IL-6-induced the redistribution of cytosolic ASIC1a channels to the cell membrane. This redistribution was accompanied by increased ASIC1a current amplitude upon activation, as well as elevated levels of phosphorylated CaMKII and ERK kinases. Additionally, we observed posttranslational modifications on the ASIC1a channel itself. These findings provide insight into a potential link between inflammatory processes and neurodegenerative mechanisms, highlighting ASIC1a channels as promising therapeutic targets in these conditions.