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Alterations in conserved Kir channel-PIP2 interactions underlie channelopathies.

Lopes C.M., Zhang H., Rohacs T., Jin T., Yang J., Logothetis D.E.

Inwardly 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 (PIP(2)). Here we identify and characterize channel-PIP(2) interactions that are conserved among Kir family members. We find basic residues that interact with PIP(2), two of which have been associated with Andersen's and Bartter's syndromes. We show that several naturally occurring mutants decrease channel-PIP(2) interactions, leading to disease.

Neuron 34:933-944(2002) [PubMed] [Europe PMC]