Validation of TREK1 ion channel activators as an immunomodulatory and neuroprotective strategy in neuroinflammation.

Schroeter CB; Nelke C; Schewe M; Spohler L; Herrmann AM; Müntefering T; Huntemann N; Kuzikov M; Gribbon P; Albrecht S; Bock S; Hundehege P; Neelsen LC; Baukrowitz T; Seebohm G; Bittner S; Wünsch B; Budde T; Ruck T; Meuth SG

Abstract

oocytes expressing TREK1 were used for further validation of these activators regarding specificity and activity. These approaches yielded three substances, E1, B3 and A2 that robustly activate TREK1. Functionally, we demonstrated that these compounds reduce levels of adhesion molecules on primary human brain and muscle endothelial cells without affecting cell viability. Finally, we studied compound A2 via voltage-clamp recordings as this activator displayed the strongest effect on adhesion molecules. Interestingly, A2 lacked TREK1 activation in the tested neuronal cell type. Taken together, this study provides data on novel TREK1 activators that might be employed to pharmacologically modulate TREK1 activity.