ATP maintains ATP-inhibited K+ channels in an operational state.

In patch-clamp records of K+ ATP channels in an insulin-secreting cell line (RINm5F) inhibition evoked by exposing the internal surface of the membrane to ATP is followed not just by the recovery of K+ ATP channel activity when the ATP is removed but by a marked activation of K+ ATP channels. This phenomenon is not a direct consequence of channel closure as inhibition induced by quinidine and quinine is followed upon the removal of the drug only by the recovery of K+ ATP channel activity and not by post-inhibitory activation. If ATP is applied to the exposed internal surface of a membrane patch when all of its K+ ATP channel have run down subsequent removal of the ATP causes their activation. The magnitude and duration of the reactivation of K+ ATP channels is shown to depend upon both the concentration of ATP and the length of time for which the membrane is exposed to ATP. We therefore have a paradoxical situation in that K+ channels which are inhibited by intracellular ATP require intracellular ATP to retain the ability to open.