ASIC1a channel and activation of ERK pathway

CASTELLANOS, LIBIA C. SALINAS; CARINA WEISSMANN; RODOLFO GATTO; OSVALDO D. UCHITEL

CORDOBA

Congreso; XXXV Reunión anual de la Sociedad Argentina de Neurociencia 2020; 2020

SAN

ASIC (Acid sensing Ion Channels) are sodium channels activated by tissue acidosis. ASIC1a is the most abundant subunit in the mammaliancentral nervous system. This subunit permeates not only sodium but, slightly, calcium ions, and so can contribute to neuronal injury inpathological conditions. Changes in regional pH levels in the brain have been observed in a number of neurological andneurodegenerative disorders and could lead to channel activation. In fact, ASIC1a channels have been lately implicated in severalneurological diseases: blocking this channel improves models of cerebral ischemia, Parkinson´s disease, Huntington´s disease.Additionally, these diseases share a feature in common: neuroinflammation. IL-6 is the main cytokine in the CNS, increased in thesediseases.It has been previously documented that ASIC1a channel activation trigger ERK phosphorylation, a pathway involved in pain, proliferationand disease.Our preliminary results show that IL-6 through its receptor induces ERK activation via ASIC1a channels through the MEK pathway in HEKcells and neuron cultures. We show that both, tozililumab (TCZ) -to block IL-6 receptors-, as well as the ASIC1a inhibitor Pctx-1, abolish ERKincreases. As expected, the inhibition of the MEK pathway (blocked by the inhibitor PD9805) is also involved in the ERK increase throughIL-6-ASIC1a. Establishing the exact role of ASIC1a, and inflammation inpathologiescould lead the way to therapies with specific channelblockers.