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The G protein-coupled inwardly rectifying potassium channels (GIRKs) are a family of lipid-gated inward-rectifier potassium ion channels which are activated (opened) by the signaling lipid PIP2 and a signal transduction cascade starting with ligand-stimulated G protein-coupled receptors (GPCRs). GPCRs in turn release activated G-protein βγ- subunits (Gβγ) from inactive heterotrimeric G protein complexes (Gαβγ). Finally, the Gβγ dimeric protein interacts with GIRK channels to open them so that they become permeable to potassium ions, resulting in hyperpolarization of the cell membrane. G protein-coupled inwardly rectifying potassium channels are a type of G protein-gated ion channels because of this direct interaction of G protein subunits with GIRK channels. The activation likely works by increasing the affinity of the channel for PIP2. In high concentration PIP2 activates the channel absent G-protein, but G-protein does not activate the channel absent PIP2.
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