Subunit stoichiometry of the pancreatic β‐cell ATP‐sensitive K+ channel

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Abstract
We have investigated the subunit stoichiometry of the pancreatic β‐cell ATP‐sensitive K+ (KATP) channel (SUR1/Kir6.2 channel) by constructing cDNA encoding a single polypeptide (βα polypeptide) consisting of a SUR1 (β) subunit and a Kir6.2 (α) subunit. 86Rb+ efflux and single‐channel properties of COS1 cells expressing βα polypeptides were similar to those of COS1 cells coexpressing α monomers and β monomers. Coexpression of βα polypeptides with α monomers inhibited the K+ currents, while coexpression with β monomers did not. We then constructed another single polypeptide (βα2) consisting of a β subunit and a dimeric repeat of the α subunit. 86Rb+ efflux from COS1 cells expressing βα2 polypeptides was small, but was restored by supplementation with β monomers. These results indicate that the activity of KATP channels is optimized when the α and β subunits are coexpressed with a molar ratio of 1:1. Since inward rectifier K+ channels are thought to function as homo‐ or hetero‐tetramers, this suggests that the KATP channel functions as a multimeric protein, most likely a hetero‐octamer composed of a tetramer of the Kir6.2 subunit and a tetramer of the SUR1 subunit.