Ion channels involved in insulin release are activated by osmotic swelling of pancreatic B-cells

Measurements of the membrane potential showed that osmotic swelling (-80 mosmol/l) of pancreatic B-cells led to a transient hyperpolarization followed by a more sustained depolarization of the cell membrane. Cell swelling triggers a transient activation of the K-ATP(+) current and of an inward current, carried by Cl-. This current was inhibited by DIDS, D6OO, and by omission of extracellular Ca2+. The depolarization opens voltage dependent L-type Ca2+ channels, thereby increasing the intracellular Ca activity ([Ca2+](i)). This effect was blunted by D600 or abolished by omission of Ca2+. Moreover, osmotic swelling transiently increased the amplitude of the Ca2+ currents. Replacement of NaCl by D-mannitol proved that the observed effects are due to an increase in cell volume and not to a reduction of extracellular Na+ or Cl-. Our results suggest that regulatory volume decrease is achieved bg activation of K+ and Cl- currents. The Cl- current is responsible for the previously described depolarization and increase in insulin release induced by osmotic cell swelling. (C) 1998 Elsevier Science B.V.