Alterations in Conserved Kir Channel-PIP2 Interactions Underlie Channelopathies

AbstractInwardly rectifying K+ (Kir) channels are important regulators of resting membrane potential and cell excitability. The activity of Kir channels is critically dependent on the integrity of channel interactions with phosphatidylinositol 4,5-bisphosphate (PIP2). Here we identify and characterize channel-PIP2 interactions that are conserved among Kir family members. We find basic residues that interact with PIP2, two of which have been associated with Andersen's and Bartter's syndromes. We show that several naturally occurring mutants decrease channel-PIP2 interactions, leading to disease