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Research Papers
Random assembly of SUR subunits in KATP channel complexes
Wayland W.L Cheng, Ailing Tong, Thomas P. Flagg and Colin G. Nichols
volume 2 | issue 1
January/February 2008Subscribe to this journal for $79/year
Sulfonylurea receptors (SURs) associate with Kir6.x subunits to form tetradimeric KATP channel complexes. SUR1 and SUR2 confer differential channel sensitivities to nucleotides and pharmacological agents, and are expressed in specific, but overlapping, tissues. This raises the question of whether these different SUR subtypes can assemble in the same channel complex and generate channels with hybrid properties. To test this, we engineered dimeric constructs of wild type or N160D mutant Kir6.2 fused to SUR1 or SUR2A. Dimeric fusions formed functional, ATP-sensitive, channels. Coexpression of weakly rectifying SUR1-Kir6.2 (WTF-1) with strongly rectifying SUR1-Kir6.2[N160D] (NDF-1) in COSm6 cells results in mixed subunit complexes that exhibit unique rectification properties. Coexpression of NDF-1 and SUR2A-Kir6.2 (WTF-2) results in similar complex rectification, reflecting the presence of SUR1- and SUR2A-containing dimers in the same channel. The data demonstrate clearly that SUR1 and SUR2A subunits associate randomly, and suggest that heteromeric channels will occur in native tissues.
Authors
Wayland W.L Cheng
Washington University School of Medicine
Ailing Tong
Washington University School of Medicine
Thomas P. Flagg
Washington University School of Medicine
Colin G. Nichols
Washington University School of Medicine