G protein-regulated inwardly rectifying potassium (GIRK1-4) channels are a family of Kir3.1-Kir3.4 ion channels that modulate cell excitability. The four different GIRK subunits are composed in different homo- and heterotetrameric combinations, which are expressed with regional specificity throughout the central nervous system and in the periphery. ML-297 is a selective GIRK1/2 activator (EC50s = 0.16 and 1.8 μM for GIRK1/2 and GIRK1/4, respectively, and is completely inactive at GIRK2/3). In two different mouse models of epilepsy, ML-297 at 60 mg/kg was shown to delay seizure onset and to prevent convulsions.
