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

K-ATP channels are heteromultimers of SUR and K(IR)6.2 C-terminal truncation of K(IR)6.2 allows surface expression of the pore. K(IR)6.2 Delta C35 channels display similar to 7-fold lower maximal open probability, similar to 35-fold reduced ATP sensitivity, reduced mean open time, a markedly increased 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 sensitivity and increase channel density in the plasma membrane, The high IC50(ATP) 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 demonstrate allosteric interaction(s) are essential for normal intrinsic activity, ATP inhibition, and trafficking of K-ATP channels, (C) 1999 Federation of European Biochemical Societies.