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

KATP channels are heteromultimers of SUR and KIR6.2. C-terminal truncation of KIR6.2 allows surface expression of the pore. KIR6.2ΔC35 channels display ∼7-fold lower maximal open probability, ∼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 ∼4 mM for KIR6.2ΔCK185Q channels results from the additive effects of SUR removal and KIR6.2 modification. The results demonstrate allosteric interaction(s) are essential for normal intrinsic activity, ATP inhibition, and trafficking of KATP channels.