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 been 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.
Proks
Peter
P
Henry Wellcome Centre for Gene Function, Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford OX1 3PT, UK.
Ashcroft
Frances M
FM
D000255:Adenosine Triphosphate / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D003198:Computer Simulation; D015640:Ion Channel Gating / Q000502:physiology*; D054086:KATP Channels / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology*; D008954:Models, Biological
D054086:KATP Channels; D000255:Adenosine Triphosphate