Random assembly of SUR subunits in K(ATP) channel complexes
Wayland W L Cheng1, Ailing Tong, Thomas P Flagg
1Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Channels (Austin, Tex.)
|August 12, 2008
Summary
Sulfonylurea receptors (SURs) can combine with different subtypes, like SUR1 and SUR2A, to form hybrid K(ATP) channels. These channels exhibit unique properties, suggesting heteromeric channels occur in native tissues.
Area of Science:
- Biochemistry
- Molecular Biology
- Channel Physiology
Background:
- Sulfonylurea receptors (SURs) and Kir6.x subunits form tetradimeric K(ATP) channel complexes.
- SUR1 and SUR2 subtypes exhibit distinct tissue expression and sensitivities to nucleotides and drugs.
Purpose of the Study:
- To investigate if different SUR subtypes (SUR1 and SUR2A) can co-assemble into the same K(ATP) channel complex.
- To determine if such co-assembly generates channels with hybrid functional properties.
Main Methods:
- Engineered dimeric constructs of Kir6.2 fused to SUR1 or SUR2A.
- Coexpressed different SUR-Kir6.2 constructs in COSm6 cells.
- Analyzed channel properties, including rectification, using electrophysiology.
Main Results:
- Dimeric fusions of SUR-Kir6.2 formed functional, ATP-sensitive channels.
- Coexpression of SUR1-Kir6.2 variants resulted in mixed complexes with unique rectification.
- Coexpression of SUR1- and SUR2A-Kir6.2 constructs yielded similar hybrid rectification properties.
Conclusions:
- SUR1 and SUR2A subunits associate randomly within K(ATP) channel complexes.
- Heteromeric K(ATP) channels, composed of different SUR subtypes, likely occur in native biological tissues.
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