Sulfhydryl oxidation induces rapid and reversible closure of the ATP‐regulated K+ channel in the pancreatic β‐cell

Abstract

Effects of sulfhydryl modification on the ATP regulated K¹ channel (K_ATP channel) in the pancreatic β-cell were studied, using the patch clamp technique. Application of the sulfhydryl oxidizing agents thimerosal and 2,2'-dithio-bis(5-nitropyridine) (DTBNP), in micromolar concentrations, caused complete inhibition of the k_ATP channel, in inside-out patches. The inhibition was rapid and was reversed by the disulfide reducing agents dithiothreitol and cysteine. Thimerosal, which is poorly membrane permeable, inhibited channel activity, only when applied to the intracellular face of the plasma membrane. In contrast, DTBNP, which is highly lipophilic, caused closure of the k_ATP channel and consequent depolarization of the membrane potential, also when applied extracellularly. Our results indicate the presence of accessible free SH groups on the cytoplasmic side of the k_ATP channel in the pancreatic β-cell. These SH groups are essential for channel function and it is possible that thiol-dependent redox mechanisms can modulate K_ATP channel activity.