ACTIVATION OF AN ANION CONDUCTANCE AND BETA-CELL DEPOLARIZATION DURING HYPOTONICALLY INDUCED INSULIN RELEASE

The perforated patch technique was used to study the effects of hypoto nic extracellular solutions on membrane potential and whole-cell curre nts in intact rat pancreatic beta-cells. A 30 % reduction in osmolarit y resulted in activation of an outwardly rectifying Cl--selective cond uctance in rat beta-cells. This conductance was inhibited by the anion channel blocker 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid ( DIDS). Exposure to a hypotonic medium also led to a transient stimulat ion of electrical activity accompanied by cell swelling and a gradual return towards control volume. These effects were also associated with the generation of an inward current at a holding potential of -70 mV, and a stimulation of insulin release from intact perifused islets. Al l of the above effects were inhibited by DIDS. It is suggested that th e stimulation of insulin release by hypotonic solutions results from a ctivation of a volume-sensitive anion conductance generating an inward current and leading to a subsequent depolarization of the beta-cell.