Regulation of mitochondrial KATP channel by redox agents

The ATP-dependent K+ channel (K-ATP) was purified from the inner mitochondrial membrane and reconstituted into lipid bilayer membranes. K-ATP activity was inhibited by high concentrations of ATP and ADP, but activated by low concentrations (up to 200 mu M) of ADP, p-Diethylaminoethylbenzoate (DEB) acted as a K-ATP opener: at micromolar concentrations, it reversed inhibition by ATP and ADP and it also prevented K-ATP rundown. Pelargonidine, extracted from flowers of Pelargonium, reduced spontaneous activity of K-ATP channels and diminished their potentiation by DEB. Their opposite action on K-ATP corresponded with their opposite redox properties in reactions with free radicals: DEB behaved as an electron donor, whereas pelargonidine acted as an electron acceptor. We hypothesize that thiol groups on mitoK(ATP) are targets for redox-active ligans. (C) 1999 Elsevier Science B.V. All rights reserved.