Oxidative stress increases potassium efflux from pancreatic islets by depletion of intracellular calcium stores

Oxidative stress to B-cells is thought to be of relevance in declining B-ce ll function and in the process of B-cell destruction. In other tissues incl uding heart, brain and liver, oxidative stress has been shown to elevate th e intracellular free calcium concentration and to provoke potassium efflux. We studied the effect of oxidative stress on Ca2+ and K+ (Rb+) outflow fro m pancreatic islets using the thiol oxidants DIP and BuOOH. Both compounds reversibly increased Rb-86(+) efflux in the presence of 3 and 16.7 mmol/l g lucose. Stimulation of Rb-86(+) efflux was also evident in the absence of c alcium. DIP evoked release of Ca-45(2+) from the pancreatic islets both in the presence or absence of extracellular calcium. Employing inhibitors of t he calcium-activated potassium channel (K-Ca) and the high conductance K+-c hannel (BKCa), the effect of DIP on Rb-86(+) efflux was slightly diminished . Tolbutamide had no effect on Rb-86(+) efflux in the presence of DIP. On t he other hand thapsigargin, a blocker of the Ca2+-ATPase of the endoplasmic reticulum, completely suppressed the DIP-mediated Rb-86(+) outflow. The da ta suggest that thiol oxidant-induced potassium efflux from pancreatic isle ts is mainly mediated through liberation of intracellular calcium and subse quent stimulation of calcium-activated potassium efflux.