In support of direct activation of GIRK channels by alcohol, a crystal structure of an alcohol bound IRK1 (Kir2.1) channel enabled the elucidation of an alcohol binding pocket in GIRK2 [10, 54] (Figure 1B). The alcohol pocket is located in the subunit interface region and is formed by the N-terminal domain and the βD-βE sheets from one subunit and the βL-βM sheets from the other subunit (Figure 1B). A residue, mGIRK2 L257 in the βD-βE sheets, is critical for alcohol-dependent activation of GIRK channel [10].
