G protein-gated Kir Channels (Kir3.x, a.k.a. K_G channels or GIRKs) are one of the targets of GPCRs, that, upon activation of the GPCR by its ligand (hormone or neurotransmitter) release two intracellular effector molecules (G_α and G_βγ) that can effectuate channel opening resulting in hyperpolarization of the cell. The K_G channels can be activated by intracellular GTP (GTPi) in the presence of agonist or by intracellular GTPγS even in the absence of agonist. After a long controversy, it was finally established that K_G channels are activated by G_βγ subunits of PTX-sensitive G proteins. Functional K_G channels are tetrameric assemblies of Kir3 family subunits and can be either homomeric or heteromeric. The composition of subunit of K_G channels varies among different cells and tissues which allows them to play diverse functional roles[1].