Article abstract
Nature Cell Biology 1, 183 - 188 (1999)
Published online: 18 June 1999 | doi:10.1038/11103
Activation of inwardly rectifying K+ channels by distinct PtdIns(4,5)P2 interactions
Hailin Zhang1, Cheng He2, Xixin Yan2, Tooraj Mirshahi2 & Diomedes E. Logothetis2
Abstract
Direct interactions of phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) with inwardly rectifying potassium channels are stronger with channels rendered constitutively active by binding to PtdIns(4,5)P2, such as IRK1, than with G-protein-gated channels (GIRKs). As a result, PtdIns(4,5)P2 alone can activate IRK1 but not GIRKs, which require extra gating molecules such as the 
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 PtdIns(4,5)P2. Between these two arginines, a conservative change of isoleucine residue 229 in GIRK4 to the corresponding leucine found in IRK1 strengthens GIRK4–PtdIns(4,5)P2 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 channel–PtdIns(4,5)P2 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.
- Howard Hughes Medical Institute, Department of Physiology and Biophysics, Mount Sinai School of Medicine, CUNY, New York, New York 10029, USA
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Department of Physiology and Biophysics, Mount Sinai School of Medicine,
CUNY, New York,
New York
10029,
USA
e-mail: logothetis@msvax.mssm.edu
