Random assembly of SUR subunits in K(ATP) channel complexes.
Sulfonylurea receptors (SURs) associate with Kir6.x subunits to form tetradimeric K(ATP) 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.
Cheng
Wayland W L
WW
Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Tong
Ailing
A
Flagg
Thomas P
TP
Nichols
Colin G
CG
D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000737:chemistry*; D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism; D002522:Chlorocebus aethiops; D019281:Dimerization; D004594:Electrophysiology; D005786:Gene Expression Regulation; D015640:Ion Channel Gating; D015233:Models, Statistical; D015221:Potassium Channels / Q000737:chemistry*; D024661:Potassium Channels, Inwardly Rectifying / Q000737:chemistry / Q000502:physiology*; D011485:Protein Binding; D011955:Receptors, Drug / Q000737:chemistry / Q000502:physiology*; D013096:Spermine / Q000737:chemistry; D064233:Sulfonylurea Receptors
D018528:ATP-Binding Cassette Transporters; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D013096:Spermine; D000255:Adenosine Triphosphate