The properties of the Kir6.1-6.2 tandem channel co-expressed with SUR2A

Functional ATP-sensitive K (K-ATP) channels have an octameric subunit struc ture with four pore-forming subunits (Kir6.x) and four sulfonylurea recepto rs (SURx). In the present study, the properties of the het eromeric K-ATP c hannel whose pore subunits are composed of Kir6.1 and Kir6.2 were examined using a heterologous expression system. In COS7 cells co-transfected with K ir6.1, Kir6.2 and SUR2A at a ratio of 1:1:2, K-ATP channels showed various unitary conductances between those of Kir6.1/SUR2A (33.6+/-4.2 pS) and Kir6 .2/SUR2A (67.1+/-1.6 pS). Kir6.1-6.2 tandem protein, constructed by fusing the C-terminus of Kir6.1 to the N-terminus of Kir6.2 with a ten glutamine l inker sequence, also formed a channel with an intermediate conductance (58. 9+/-1.5 pS). Kir6.2 and Kir6.1-6.2 showed similar sensitivity to ATP(4-): h alf-maximal inhibition (IC50) was obtained at 14.1+/-12.8 muM and 17.6+/-9. 6 muM, respectively. In the presence of Mg2+, Kir6.1-6.2 was significantly less sensitive than Kir6.2 to MgATP (IC50=95.5+/-49.6 muM versus 18.9+/-5.0 muM). These results suggest that Kir6.1 and Kir6.2 are endowed with the po tential to form a heteromeric K-ATP channel, which has a low sensitivity to MgATP.