channel in cells where PIP2 levels are depleted using a voltage-activated phosphatase (Dr-VSP) that removes the 5′ phosphate (Bodhinathan and Slesinger, 2013). Moreover, presence of alcohol in the pocket slows down that rate of PIP2 dissociation from the channel, suggesting an increase the relative affinity between PIP2 and the GIRK channel. Thus, structural changes in the PIP2 binding interface in GIRK channels is a critical gating step for two distinct pathways for activating GIRK channels, slower Gβγ-dependent activation and rapid alcohol-dependent activation.
