Sulfonylurea receptors set the maximal open probability, ATP sensitivity and plasma membrane density of K-ATP channels

K-ATP channels are heteromultimers of SUR and K(IR)6.2 C-terminal truncatio n of K(IR)6.2 allows surface expression of the pore. K(IR)6.2 Delta C35 cha nnels display similar to 7-fold lower maximal open probability, similar to 35-fold reduced ATP sensitivity, reduced mean open time, a markedly increas ed transition rate from a burst into a long-lived closed state, and have no counterpart in vivo. SUR1 and SUR2A restore wild-type bursting, ATP sensit ivity and increase channel density in the plasma membrane, The high IC50(AT P) of similar to 4 mM for K(IR)6.2 Delta C-K185Q channels results from the additive effects of SUR removal and K(IR)6.2 modification. The results demo nstrate allosteric interaction(s) are essential for normal intrinsic activi ty, ATP inhibition, and trafficking of K-ATP channels, (C) 1999 Federation of European Biochemical Societies.