Journal article
Direct activation of inward rectifier potassium channels by PIP 2 and its stabilization by Gβγ
Nature (London), Vol.391(6669), pp.803-806
02/19/1998
DOI: 10.1038/35882
Abstract
Inward rectifier K+ channels, which modulate electrical activity in many cell types, are regulated by protein kinases,, guanine-nucleotide-binding proteins (G proteins) and probably actin cytoskeleton. Generation of phosphatidylinositol 4,5-bisphosphate (PIP2) by ATP-dependent lipid kinases is known to activate inward rectifier K+ channels in cardiac membrane patches. Herewe report that several cloned inward rectifier K+ channels directly bind PIP2, and that this binding correlates with channel activity. Application of ATP or PIP2 liposomes activates the cloned channels. Stabilized by lipid phosphatase inhibitors, PIP2 antibodies potently inhibit each channel with a unique rate (GIRK1/4 (refs 3-5) GIRK2 (ref. 6) > IRK1 (ref. 10) ROMK (ref. 11)). Consistent with the faster dissociation of PIP2 from the GIRK channels, the carboxy terminus of GIRK1 binds 3H-PIP2 liposomes more weakly than does that of IRK1 or ROMK1. Mutation of a conserved arginine to glutamine at position 188 reduces the ability of ROMK1 to bind PIP2 and increases its sensitivity to inhibition by PIP2 antibodies. Interactions between GIRK channels and PIP2 are modulated by the βγ subunits of the G protein (Gβγ). When GIRK1/4 channels are allowed to run down completely, they are not activated by addition of Gβγ alone, but application of PIP2 activates them in minutes without Gβγ and in just seconds with Gβγ. Finally, coexpression of Gβγ with GIRK channels slows the inhibition of K+ currents by PIP2 antibodies by more than 10-fold. Thus Gβγ activates GIRK channels by stabilizing interactions between PIP2 and the K+ channel.
Details
- Title: Subtitle
- Direct activation of inward rectifier potassium channels by PIP 2 and its stabilization by Gβγ
- Creators
- Chou-Long Huang - Internal MedicineSiyi Feng - The University of Texas Southwestern Medical CenterDonald W Hilgemann - The University of Texas Southwestern Medical Center
- Resource Type
- Journal article
- Publication Details
- Nature (London), Vol.391(6669), pp.803-806
- DOI
- 10.1038/35882
- ISSN
- 0028-0836
- eISSN
- 1476-4687
- Language
- English
- Date published
- 02/19/1998
- Academic Unit
- Nephrology; Internal Medicine
- Record Identifier
- 9984359869902771
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