Somatostatin induces hyperpolarization in pancreatic islet alpha cells by activating a G protein-gated K+ channel.

Somatostatin inhibits glucagon-secretion from pancreatic alpha cells but its underlying mechanism is unknown. In mouse alpha cells, we found that somatostatin induced prominent hyperpolarization by activating a K+ channel, which was unaffected by tolbutamide but prevented by pre-treating the cells with pertussis toxin. The K+ channel was activated by intracellular GTP (with somatostatin), GTPgammaS or Gbetagamma subunits. It was thus identified as a G protein-gated K+ (K(G)) channel. RT-PCR and immunohistochemical analyses suggested the K(G) channel to be composed of Kir3.2c and Kir3.4. This study identified a novel ionic mechanism involved in somatostatin-inhibition of glucagon-secretion from pancreatic alpha cells.