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A G protein consists of three subunits: α, β and γ. Before activation, they are bound together. Gβ and Gγ are tightly bound, whereas Gα may dissociate from Gβγ, depending on whether it is bound with GDP (guanosine diphosphate) or GTP (guanosine triphosphate). In the resting state, Gα is bound with GDP, facilitating the combination of three subunits. After activation, the GDP bound with Gα will be replaced by GTP, promoting dissociation of Gα from Gβγ. The separated Gα and Gβγ can then act on specific targets, known as effectors. The GTP on Gα cannot last long, because Gα has the enzymatic activity to hydrolyze it into GDP, thereby returning to the resting state (Figure 6-1).

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Figure 6-1. The G protein cycle. (a) In the resting state, Gα is bound with GDP, facilitating the combination of three subunits. (b) The G-protein coupled receptor is activated by its agonist, resulting in the substitution of GDP on Gα by GTP. (c) Gα dissociates from Gβγ. (d) GTP is hydrolyzed by Gα to GDP, returning to the resting state. [Source: Wikipedia]

Gα has several isoforms, such as Gαs, Gαi and Gαo. The G protein coupled with GIRK channels comprises Gαi or Gαo. However, GIRK channels do not directly interact with Gα, but are directly activated by Gβγ. In other words, GIRK channels are the effectors of Gβγ, not Gα (Luscher and Slesinger, 2010).