excitability (Glaaser and Slesinger, 2015, Luscher and Slesinger, 2010, Zhao et al., 2021). Activation of inhibitory G protein coupled receptors (GPCRs) via ligand binding leads to GIRK2 activation via Gβγ, resulting in outward potassium flux through the channel and subsequent inhibition of neuronal firing (Reuveny et al., 1994). In rodent studies, GIRK channels are implicated in alcohol-related behaviors (Blednov et al., 2001b, Blednov et al., 2001a, Hill et al., 2003, Kozell et al., 2009, Herman et al., 2015), and in humans, GIRK3 has been linked with AUD (Sanchez-Roige et al., 2019, Kozell et al., 2018), potentially through effects on GIRK2 trafficking (Ma et al., 2002). In addition, GIRK channels can be directly potentiated by alcohol through interaction with a hydrophobic pocket in the channel (Aryal et al., 2009, Bodhinathan and Slesinger, 2014).
