Modeling K-ATP channel gating and its regulation

ATP-sensitive potassium (K-ATP) channels Couple cell metabolism to plasmalemmal potassium fluxes in a variety of cell types. The activity of these channels is primarily determined by intracellular adenosine nucleotides, which have both inhibitory and stimulatory effects. The role of K-ATP channels has beer) studied most extensively in pancreatic beta-cells, where they link glucose metabolism to insulin secretion. Many mutations in K-ATP channel subunits (Kir6.2, SUR1) have been identified that cause either neonatal diabetes or congenital hyperinsulinism. Thus, a mechanistic understanding of K-ATP channel behavior is necessary for modeling beta-cell electrical activity and insulin release in both health and disease. Here, we review recent advances in the K-ATP channel structure and function. We focus on the Molecular mechanisms of K-ATP channel gating by adenosine nucleotides, phospholipids and sulphonylureas and consider the advantages and limitations of various mathematical models of macroscopic and single-channel K-ATP currents. Finally, we outline future directions for the development of more realistic models of K-ATP channel gating. (C) 2008 Elsevier Ltd. All rights reserved.