ATP-sensitive K+ channels in β-cells;: their role in stimulus-secretion coupling

Here we describe the relationship between the control of K-ATP channel function in pancreatic beta-cells and the regulation of insulin secretion. Focus is placed upon two areas of complementary activity in the field of ion channels and stimulus-response coupling in beta-cell. First, the molecular biology of the beta-cell KATP channels, where studies have demonstrated that the channel is a novel heteromultimeric complex of an ATP-binding cassette protein, designated SUR1, and a KC channel. And secondly, we review the evidence that pathophysiology of the beta-cell occurs in association with loss of KATP channel function. In this part of the review we document how gene variations in either of the channel subunits leads to unregulated, and inappropriately high rates of insulin secretion in humans, and the condition persistent hyperinsulinaemic hypoglycaemia of infancy It is now clear that not only do KATP channels govern the onset of depolarisation-response coupling in beta-cells, but that they also play a role in insulin-secreting cell survival by preventing insulin hypersecretion and the onset of apoptosis.