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- Title
Activation of inwardly rectifying K<sup>+</sup> channels by distinct PtdIns(4,5)P<sub>2</sub> interactions.
- Authors
Zhang, Hailin; He, Cheng; Yan, Xixin; Mirshahi, Tooraj; Logothetis, Diomedes E.
- Abstract
Direct interactions of phosphatidylinositol-4,5-bisphosphate (Ptdlns(4,5)P[sub 2]) with inwardly rectifying potassium channels are stronger with channels rendered constitutively active by binding to Ptdlns(4,5)P[sub 2], such as IRK1, than with G-protein-gated channels (GIRKs). As a result, Ptdlns(4,5)P[sub 2] alone can activate IRK1 but not GIRKs, which require extra gating molecules such as the βγ subunits of G proteins or sodium ions. Here we identify two conserved residues near the inner-membrane interface of these channels that are critical in interactions with Ptdlns(4,5)P[sub 2]. Between these two arginines, a conservative change of isoleucine residue 229 in GIRK4 to the corresponding leucine found in IRK1 strengthens GIRK4-Ptdlns(4,5)P[sub 2] interactions, eliminating the need for extra gating molecules. A negatively charged GIRK4 residue, two positions away from the most strongly interacting arginine, mediates stimulation of channel activity by sodium by strengthening channeI-Ptdlns(4,5)P[sub 2] interactions. Our results provide a mechanistic framework for understanding how distinct gating mechanisms of inwardly rectifying potassium channels allow these channels to subserve their physiological roles.
- Publication
Nature Cell Biology, 1999, Vol 1, Issue 3, p183
- ISSN
1465-7392
- Publication type
Academic Journal
- DOI
10.1038/11103