SULFHYDRYL OXIDATION INDUCES RAPID AND REVERSIBLE CLOSURE OF THE ATP-REGULATED K+ CHANNEL IN THE PANCREATIC BETA-CELL

Effects of sulfhydryl modification on the ATP regulated K+ channel (K(ATP) channel) in the pancreatic beta-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 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 beta-cell. These SH groups are essential for channel function and it is possible that thiol-dependent redox mechanisms can modulate K(ATP) channel activity.